Mutation Health Dictionary

A chemical or physical agent that has the property of increasing the rate of MUTATION among CELLS. A mutagen does not usually increase the range of mutations. Chemicals, ionising radiation, and viruses may act as mutagens.... mutagen

The commonest form of inherited retarded growth. It is a dominant hereditary disorder of endochondral ossi?cation, caused by mutations of ?broblast growth factor receptor 3 genes.The long bones of the arms and legs fail to grow properly, while the trunk and head develop normally. Achondroplasia affects both sexes and, while many infants are stillborn or die soon after birth, those who survive have normal intelligence, a normal expectation of life and good health.... achondroplasia

(1) A term describing tissues of the body that do not form any part of the reproductive process. A somatic MUTATION cannot be passed on to the next generation.

(2) It is also used to refer to the body rather than the mind (see PSYCHOSOMATIC DISEASES).... somatic

A rearrangement of the chromosomes inside a person’s cells; it is a type of mutation. Sections of chromosomes may be exchanged or the main parts of 2 chromosomes may be joined. A translocation may be inherited or acquired as the result of a new mutation.

A translocation often has no obvious effect, and causes no abnormality.

However, in some cases, it can mean that some of the affected person’s egg or sperm cells carry too much or too little chromosomal material, which may cause a chromosomal abnormality, such as Down’s syndrome, in his or her children.... translocation

These are caused when there are mutations or other abnormalities which disrupt the code of a gene or set of GENES. These are divided into autosomal (one of the 44 CHROMOSOMES which are not sex-linked), dominant, autosomal recessive, sex-linked and polygenic disorders.

Dominant genes A dominant characteristic is an e?ect which is produced whenever a gene or gene defect is present. If a disease is due to a dominant gene, those affected are heterozygous – that is, they only carry a fault in the gene on one of the pair of chromosomes concerned. A?ected people married to normal individuals transmit the gene directly to one-half of the children, although this is a random event just like tossing a coin. HUNTINGTON’S CHOREA is due to the inheritance of a dominant gene, as is neuro?bromatosis (see VON RECKLINGHAUSEN’S DISEASE) and familial adenomatous POLYPOSIS of the COLON. ACHONDROPLASIA is an example of a disorder in which there is a high frequency of a new dominant mutation, for the majority of affected people have normal parents and siblings. However, the chances of the children of a parent with the condition being affected are one in two, as with any other dominant characteristic. Other diseases inherited as dominant characteristics include spherocytosis, haemorrhagic telangiectasia and adult polycystic kidney disease.

Recessive genes If a disease is due to a recessive gene, those affected must have the faulty gene on both copies of the chromosome pair (i.e. be homozygous). The possession of a single recessive gene does not result in overt disease, and the bearer usually carries this potentially unfavourable gene without knowing it. If that person marries another carrier of the same recessive gene, there is a one-in-four chance that their children will receive the gene in a double dose, and so have the disease. If an individual sufferer from a recessive disease marries an apparently normal person who is a heterozygous carrier of the same gene, one-half of the children will be affected and the other half will be carriers of the disease. The commonest of such recessive conditions in Britain is CYSTIC FIBROSIS, which affects about one child in 2,000. Approximately 5 per cent of the population carry a faulty copy of the gene. Most of the inborn errors of metabolism, such as PHENYLKETONURIA, GALACTOSAEMIA and congenital adrenal hyperplasia (see ADRENOGENITAL SYNDROME), are due to recessive genes.

There are characteristics which may be incompletely recessive – that is, neither completely dominant nor completely recessive – and the heterozygotus person, who bears the gene in a single dose, may have a slight defect whilst the homozygotus, with a double dose of the gene, has a severe illness. The sickle-cell trait is a result of the sickle-cell gene in single dose, and sickle-cell ANAEMIA is the consequence of a double dose.

Sex-linked genes If a condition is sex-linked, affected males are homozygous for the mutated gene as they carry it on their single X chromosome. The X chromosome carries many genes, while the Y chromosome bears few genes, if any, other than those determining masculinity. The genes on the X chromosome of the male are thus not matched by corresponding genes on the Y chromosome, so that there is no chance of the Y chromosome neutralising any recessive trait on the X chromosome. A recessive gene can therefore produce disease, since it will not be suppressed by the normal gene of the homologous chromosome. The same recessive gene on the X chromosome of the female will be suppressed by the normal gene on the other X chromosome. Such sex-linked conditions include HAEMOPHILIA, CHRISTMAS DISEASE, DUCHENNE MUSCULAR

DYSTROPHY (see also MUSCLES, DISORDERS OF – Myopathy) and nephrogenic DIABETES INSIPIDUS.

If the mother of an affected child has another male relative affected, she is a heterozygote carrier; half her sons will have the disease and half her daughters will be carriers. The sister of a haemophiliac thus has a 50 per cent chance of being a carrier. An affected male cannot transmit the gene to his son because the X chromosome of the son must come from the mother; all his daughters, however, will be carriers as the X chromosome for the father must be transmitted to all his daughters. Hence sex-linked recessive characteristics cannot be passed from father to son. Sporadic cases may be the result of a new mutation, in which case the mother is not the carrier and is not likely to have further affected children. It is probable that one-third of haemophiliacs arise as a result of fresh mutations, and these patients will be the ?rst in the families to be affected. Sometimes the carrier of a sex-linked recessive gene can be identi?ed. The sex-linked variety of retinitis pigmentosa (see EYE, DISORDERS OF) can often be detected by ophthalmoscopic examination.

A few rare disorders are due to dominant genes carried on the X chromosome. An example of such a condition is familial hypophosphataemia with vitamin-D-resistant RICKETS.

Polygenic inheritance In many inherited conditions, the disease is due to the combined action of several genes; the genetic element is then called multi-factorial or polygenic. In this situation there would be an increased incidence of the disease in the families concerned, but it will not follow the Mendelian (see MENDELISM; GENETIC CODE) ratio. The greater the number of independent genes involved in determining a certain disease, the more complicated will be the pattern of inheritance. Furthermore, many inherited disorders are the result of a combination of genetic and environmental in?uences. DIABETES MELLITUS is the most familiar of such multi-factorial inheritance. The predisposition to develop diabetes is an inherited characteristic, although the gene is not always able to express itself: this is called incomplete penetrance. Whether or not the individual with a genetic predisposition towards the disease actually develops diabetes will also depend on environmental factors. Diabetes is more common in the relatives of diabetic patients, and even more so amongst identical twins. Non-genetic factors which are important in precipitating overt disease are obesity, excessive intake of carbohydrate foods, and pregnancy.

SCHIZOPHRENIA is another example of the combined effects of genetic and environmental in?uences in precipitating disease. The risk of schizophrenia in a child, one of whose parents has the disease, is one in ten, but this ?gure is modi?ed by the early environment of the child.... genetic disorders

An aberrant variety of one of the proteins, called PrP, in a brain cell. The result of a gene mutation (see GENES), prions are stable, resistant to radiation and impervious to the normal cellular processes of degradation. They seem to react with normal PrP, turning it into an abnormal type that then accumulates in brain tissue. Prions are believed to be the infectious agents that cause a group of serious neurological disorders called spongiform encephalopathies. CREUTZFELDT-JAKOB DISEASE (CJD), the new variant of CJD linked with BOVINE SPONGIFORM ENCEPHALOPATHY (BSE), and KURU – a neurological disorder found in a cannibal tribe in New Guinea – are all diseases in this group that occur in humans. The prion disorders have a long latent period between infection and manifestation of symptoms; they are hard to diagnose until autopsy and there is no cure as yet.... prion

A unit of the material of heredity. A gene corresponds to a particular area of DNA within a chromosome. There are about 30,000 different genes arranged on the 23 pairs of chromosomes. These genes control the development and functioning of organs and body systems, providing an “instruction manual” for an individual’s growth, survival, reproduction, and possibly also for aging and death. Genes also play a part, together with environmental factors, in determining a person’s intelligence, personality, and behaviour.

Genes fulfil these functions by directing the manufacture of proteins. Many proteins have a structural or catalytic role in the body. Others switch genes “on” or “off”. The genes that make these regulatory proteins are called control genes. The activities of control genes determine the specialization of cells; within any cell some genes are active and others idle, according to its particular function. If the control genes are disrupted, cells lose their specialist abilities and multiply out of control; this is the probable mechanism by which cancers form (see carcinogenesis; oncogenes).Each of a person’s body cells contains an identical set of genes because all the cells are derived, by a process of division, from a single fertilized egg, and with each division the genes are copied to each offspring cell (see mitosis; meiosis). Occasionally, a fault occurs in the copying process, leading to a mutation. The gene at any particular location on a chromosome can exist in any of various forms, called alleles. If the effects of an allele mask those of the allele at the same location on its partner chromosome, it is called dominant. The masked allele is recessive. (See also genetic code; inheritance.)... gene

Acquired Immune De?ciency Syndrome (AIDS) is the clinical manifestation of infection with Human Immunode?ciency Virus (HIV). HIV belongs to the retroviruses, which in turn belong to the lentiviruses (characterised by slow onset of disease). There are two main HIV strains: HIV-1, by far the commonest; and HIV-2, which is prevalent in Western Africa (including Ivory Coast, Gambia, Mali, Nigeria and Sierra Leone). HIV attacks the human immune system (see IMMUNITY) so that the infected person becomes susceptible to opportunistic infections, such as TUBERCULOSIS, PNEUMONIA, DIARRHOEA, MENINGITIS and tumours such as KAPOSI’S SARCOMA. AIDS is thus the disease syndrome associated with advanced HIV infection.

Both HIV-1 and HIV-2 are predominantly sexually transmitted and both are associated with secondary opportunistic infections. However, HIV-2 seems to result in slower damage to the immune system. HIV-1 is known to mutate rapidly and has given rise to other subtypes.

HIV is thought to have occurred in humans in the 1950s, but whether or not it infected humans from another primate species is uncertain. It became widespread in the 1970s but its latency in causing symptoms meant that the epidemic was not noticed until the following decade. Although it is a sexually transmitted disease, it can also be transmitted by intravenous drug use (through sharing an infected needle), blood transfusions with infected blood (hence the importance of e?ective national blood-screening programmes), organ donation, and occupationally (see health-care workers, below). Babies born of HIV-positive mothers can be infected before or during birth, or through breast feeding.

Although HIV is most likely to occur in blood, semen or vaginal ?uid, it has been found in saliva and tears (but not sweat); however, there is no evidence that the virus can be transmitted from these two body ?uids. There is also no evidence that HIV can be transmitted by biting insects (such as mosquitoes). HIV does not survive well in the environment and is rapidly destroyed through drying.

Prevalence At the end of 2003 an estimated 42 million people globally were infected with HIV – up from 40 million two years earlier. About one-third of those with HIV/AIDS are aged 15–24 and most are unaware that they are carrying the virus. During 2003 it is estimated that 5 million adults and children worldwide were newly infected with HIV, and that 3 million adults and children died. In Africa in 2003,

3.4 million people were newly infected and 2.3 million died, with more than 28 million carrying the virus. HIV/AIDS was the leading cause of death in sub-Saharan Africa where over half of the infections were in women and 90 per cent of cases resulted from heterosexual sex. In some southern African countries, one in three pregnant women had HIV.

In Asia and the Paci?c there were 1.2 million new infections and 435,000 deaths. The area with the fastest-growing epidemic is Eastern Europe, especially the Russian Federation where in 2002 around a million people had HIV and there were an estimated 250,000 new infections, with intravenous drug use a key contributor to this ?gure. Seventy-?ve per cent of cases occurred in men, with male-to-male sexual transmission an important cause of infection, though heterosexual activity is a rising cause of infection.

At the end of 2002 the UK had an estimated 55,900 HIV-infected adults aged between 15 and 59. More than 3,600 individuals were newly diagnosed with the infection in 2000, the highest annual ?gure since the epidemic started

– in 1998 the ?gure was 2,817 and in 1999 just over 3,000 (Department of Health and Communicable Disease Surveillance Centre). The incidence of AIDS in the UK has declined sharply since the introduction of highly active antiretroviral therapy (HAART) and HIV-related deaths have also fallen: in 2002 there were 777 reported new AIDS cases and 395 deaths, compared with 1,769 and 1,719 respectively in 1995. (Sources: UNAIDS and WHO, AIDS Epidemic Update, December 2001; Public Health Laboratory Services AIDS and STD Centre Communicable Disease Surveillance and Scottish Centre for Infection and Environmental Health, Quarterly Surveillance Tables.)

Poverty is strongly linked to the spread of AIDS, for various reasons including lack of health education; lack of e?ective public-health awareness; women having little control over sexual behaviour and contraception; and, by comparison with the developed world, little or no access to antiretroviral drugs.

Pathogenesis The cellular target of HIV infection is a subset of white blood cells called T-lymphocytes (see LYMPHOCYTE) which carry the CD4 surface receptor. These so-called ‘helper T-cells’ are vital to the function of cell-mediated immunity. Infection of these cells leads to their destruction (HIV replicates at an enormous rate – 109) and over the course of several years the body is unable to generate suf?cient new cells to keep pace. This leads to progressive destruction of the body’s immune capabilities, evidenced clinically by the development of opportunistic infection and unusual tumours.

Monitoring of clinical progression It is possible to measure the number of viral particles present in the plasma. This gives an accurate guide to the likely progression rate, which will be slow in those individuals with fewer than 10,000 particles per ml of plasma but progressively more rapid above this ?gure. The main clinical monitoring of the immune system is through the numbers of CD4 lymphocytes in the blood. The normal count is around 850 cells per ml and, without treatment, eventual progression to AIDS is likely in those individuals whose CD4 count falls below 500 per ml. Opportunistic infections occur most frequently when the count falls below 200 per ml: most such infections are treatable, and death is only likely when the CD4 count falls below 50 cells per ml when infection is developed with organisms that are di?cult to treat because of their low intrinsic virulence.

Simple, cheap and highly accurate tests are available to detect HIV antibodies in the serum. These normally occur within three months of infection and remain the cornerstone of the diagnosis.

Clinical features Most infected individuals have a viral illness some three weeks after contact with HIV. The clinical features are often non-speci?c and remain undiagnosed but include a ?ne red rash, large lymph nodes, an in?uenza-like illness, cerebral involvement and sometimes the development of opportunistic infections. The antibody test may be negative at this stage but there are usually high levels of virus particles in the blood. The antibody test is virtually always positive within three months of infection. HIV infection is often subsequently asymptomatic for a period of ten years or more, although in most patients progressive immune destruction is occurring during this time and a variety of minor opportunistic infections such as HERPES ZOSTER or oral thrush (see CANDIDA) do occur. In addition, generalised LYMPHADENOPATHY is present in a third of patients and some suffer from severe malaise, weight loss, night sweats, mild fever, ANAEMIA or easy bruising due to THROMBOCYTOPENIA.

The presentation of opportunistic infection is highly variable but usually involves either the CENTRAL NERVOUS SYSTEM, the gastrointestinal tract or the LUNGS. Patients may present with a sudden onset of a neurological de?cit or EPILEPSY due to a sudden onset of a STROKE-like syndrome, or epilepsy due to a space-occupying lesion in the brain – most commonly TOXOPLASMOSIS. In late disease, HIV infection of the central nervous system itself may produce progressive memory loss, impaired concentration and mental slowness called AIDS DEMENTIA. A wide variety of opportunistic PROTOZOA or viruses produces DYSPHAGIA, DIARRHOEA and wasting. In the respiratory system the commonest opportunistic infection associated with AIDS, pneumonia, produces severe shortness of breath and sometimes CYANOSIS, usually with a striking lack of clinical signs in the chest.

In very late HIV infection, when the CD4 count has fallen below 50 cells per ml, infection with CYTOMEGALOVIRUS may produce progressive retinal necrosis (see EYE, DISORDERS OF) which will lead to blindness if untreated, as well as a variety of gastrointestinal symptoms. At this stage, infection with atypical mycobacteria is also common, producing severe anaemia, wasting and fevers. The commonest tumour associated with HIV is Kaposi’s sarcoma which produces purplish skin lesions. This and nonHodgkin’s lymphoma (see LYMPHOMA), which is a hundred times more frequent among HIV-positive individuals than in the general population, are likely to be associated with or caused by opportunistic viral infections.

Prevention There is, as yet, no vaccine to prevent HIV infection. Vaccine development has been hampered

by the large number of new HIV strains generated through frequent mutation and recombination.

because HIV can be transmitted as free virus and in infected cells.

because HIV infects helper T-cells – the very cells involved in the immune response. There are, however, numerous research pro

grammes underway to develop vaccines that are either prophylactic or therapeutic. Vaccine-development strategies have included: recombinant-vector vaccines, in which a live bacterium or virus is genetically modi?ed to carry one or more of the HIV genes; subunit vaccines, consisting of small regions of the HIV genome designed to induce an immune response without infection; modi?ed live HIV, which has had its disease-promoting genes removed; and DNA vaccines – small loops of DNA (plasmids) containing viral genes – that make the host cells produce non-infectious viral proteins which, in turn, trigger an immune response and prime the immune system against future infection with real virus.

In the absence of an e?ective vaccine, preventing exposure remains the chief strategy in reducing the spread of HIV. Used properly, condoms are an extremely e?ective method of preventing exposure to HIV during sexual intercourse and remain the most important public-health approach to countering the further acceleration of the AIDS epidemic. The spermicide nonoxynol-9, which is often included with condoms, is known to kill HIV in vitro; however, its e?ectiveness in preventing HIV infection during intercourse is not known.

Public-health strategies must be focused on avoiding high-risk behaviour and, particularly in developing countries, empowering women to have more control over their lives, both economically and socially. In many of the poorer regions of the world, women are economically dependent on men and refusing sex, or insisting on condom use, even when they know their partners are HIV positive, is not a straightforward option. Poverty also forces many women into the sex industry where they are at greater risk of infection.

Cultural problems in gaining acceptance for universal condom-use by men in some developing countries suggests that other preventive strategies should also be considered. Microbicides used as vaginal sprays or ‘chemical condoms’ have the potential to give women more direct control over their exposure risk, and research is underway to develop suitable products.

Epidemiological studies suggest that male circumcision may o?er some protection against HIV infection, although more research is needed before this can be an established public-health strategy. Globally, about 70 per cent of infected men have acquired the virus through unprotected vaginal sex; in these men, infection is likely to have occurred through the penis with the mucosal epithelia of the inner surface of the foreskin and the frenulum considered the most likely sites for infection. It is suggested that in circumcised men, the glans may become keratinised and thus less likely to facilitate infection. Circumcision may also reduce the risk of lesions caused by other sexually transmitted disease.

Treatment AIDS/HIV treatment can be categorised as speci?c therapies for the individual opportunistic infections – which ultimately cause death – and highly active antiretroviral therapy (HAART) designed to reduce viral load and replication. HAART is also the most e?ective way of preventing opportunistic infections, and has had a signi?cant impact in delaying the onset of AIDS in HIV-positive individuals in developed countries.

Four classes of drugs are currently in use. Nucleoside analogues, including ZIDOVUDINE and DIDANOSINE, interfere with the activity of the unique enzyme of the retrovirus reverse transcriptase which is essential for replication. Nucleotide analogues, such as tenofovir, act in the same way but require no intracellular activation. Non-nucleoside reverse transcriptase inhibitors, such as nevirapine and EFAVIRENZ, act by a di?erent mechanism on the same enzyme. The most potent single agents against HIV are the protease inhibitors, such as lopinavir, which render a unique viral enzyme ineffective. These drugs are used in a variety of combinations in an attempt to reduce the plasma HIV viral load to below detectable limits, which is achieved in approximately 90 per cent of patients who have not previously received therapy. This usually also produces a profound rise in CD4 count. It is likely, however, that such treatments need to be lifelong – and since they are associated with toxicities, long-term adherence is di?cult. Thus the optimum time for treatment intervention remains controversial, with some clinicians believing that this should be governed by the viral load rising above 10,000 copies, and others that it should primarily be designed to prevent the development of opportunistic infections – thus, that initiation of therapy should be guided more by the CD4 count.

It should be noted that the drug regimens have been devised for infection with HIV-1; it is not known how e?ective they are at treating infection with HIV-2.

HIV and pregnancy An HIV-positive woman can transmit the virus to her fetus, with the risk of infection being particularly high during parturition; however, the risk of perinatal HIV transmission can be reduced by antiviral drug therapy. In the UK, HIV testing is available to all women as part of antenatal care. The bene?ts of antenatal HIV testing in countries where antiviral drugs are not available are questionable. An HIV-positive woman might be advised not to breast feed because of the risks of transmitting HIV via breastmilk, but there may be a greater risk associated with not breast feeding at all. Babies in many poor communities are thought to be at high risk of infectious diseases and malnutrition if they are not breast fed and may thus be at greater overall risk of death during infancy.

Counselling Con?dential counselling is an essential part of AIDS management, both in terms of supporting the psychological wellbeing of the individual and in dealing with issues such as family relations, sexual partners and implications for employment (e.g. for health-care workers). Counsellors must be particularly sensitive to culture and lifestyle issues. Counselling is essential both before an HIV test is taken and when the results are revealed.

Health-care workers Health-care workers may be at risk of occupational exposure to HIV, either through undertaking invasive procedures or through accidental exposure to infected blood from a contaminated needle (needlestick injury). Needlestick injuries are frequent in health care – as many as 600,000 to 800,000 are thought to occur annually in the United States. Transmission is much more likely where the worker has been exposed to HIV through a needlestick injury or deep cut with a contaminated instrument than through exposure of mucous membranes to contaminated blood or body ?uids. However, even where exposure occurs through a needlestick injury, the risk of seroconversion is much lower than with a similar exposure to hepatitis C or hepatitis B. A percutaneous exposure to HIV-infected blood in a health-care setting is thought to carry a risk of about one infection per 300 injuries (one in 1,000 for mucous-membrane exposure), compared with one in 30 for hepatitis C, and one in three for hepatitis B (when the source patient is e-antigen positive).

In the event of an injury, health-care workers are advised to report the incident immediately where, depending on a risk assessment, they may be o?ered post-exposure prophylaxis (PEP). They should also wash the contaminated area with soap and water (but without scrubbing) and, if appropriate, encourage bleeding at the site of injury. PEP, using a combination of antiretroviral drugs (in a similar regimen to HAART – see above), is thought to greatly reduce the chances of seroconversion; it should be commenced as soon as possible, preferably within one or two hours of the injury. Although PEP is available, safe systems of work are considered to o?er the greatest protection. Double-gloving (latex gloves remove much of the blood from the surface of the needle during a needlestick), correct use of sharps containers (for used needles and instruments), avoiding the resheathing of used needles, reduction in the number of blood samples taken from a patient, safer-needle devices (such as needles that self-blunt after use) and needleless drug administration are all thought to reduce the risk of exposure to HIV and other blood-borne viruses. Although there have been numerous cases of health-care workers developing HIV through occupational exposure, there is little evidence of health-care workers passing HIV to their patients through normal medical procedures.... aids/hiv

Alzheimer’s disease is a progressive degenerating process of neural tissue affecting mainly the frontal and temporal lobes of the BRAIN in middle and late life. There is probably a genetic component to Alzheimer’s disease, but early-onset Alzheimer’s is linked to certain mutations, or changes, in three particular GENES. Examination of affected brains shows ‘senile plaques’ containing an amyloid-like material distributed throughout an atrophied cortex (see AMYLOID PLAQUES). Many remaining neurons, or nerve cells, show changes in their NEUROFIBRILS which thicken and twist into ‘neuro?brillary tangles’. First symptoms are psychological with insidious impairment of recent memory and disorientation in time and space. This becomes increasingly associated with diffculties in judgement, comprehension and abstract reasoning. After very few years, progressive neurological deterioration produces poor gait, immobility and death. When assessment has found no other organic cause for an affected individual’s symptoms, treatment is primarily palliative. The essential part of treatment is the provision of appropriate nursing and social care, with strong support being given to the relatives or other carers for whom looking after sufferers is a prolonged and onerous burden. Proper diet and exercise are helpful, as is keeping the individual occupied. If possible, sufferers should stay in familiar surroundings with day-care and short-stay institutional facilities a useful way of maintaining them at home for as long as possible.

TRANQUILLISERS can help control di?cult behaviour and sleeplessness but should be used with care. Recently drugs such as DONEPEZIL and RIVASTIGMINE, which retard the breakdown of ACETYLCHOLINE, may check

– but not cure – this distressing condition. About 40 per cent of those with DEMENTIA improve.

Research is in progress to transplant healthy nerve cells (developed from stem cells) into the brain tissue of patients with Alzheimer’s disease with the aim of improving brain function.

The rising proportion of elderly people in the population is resulting in a rising incidence of Alzheimer’s, which is rare before the age of 60 but increases steadily thereafter so that 30 per cent of people over the age of 84 are affected.... alzheimer’s disease

A rapidly progressive, fatal, degenerative disease in humans caused by an abnormal PRION protein. There are three aetiological forms of CJD: sporadic, IATROGENIC, and inherited. Sporadic CJD occurs randomly in all countries and has an annual incidence of one per million. Iatrogenic CJD is caused by accidental exposure to human prions through medical and surgical procedures (and cannibalism in the case of the human prion disease known as kuru that occurs in a tribe in New Guinea, where it is called the trembling disease). Inherited or familial CJD accounts for 15 per cent of human prion disease and is caused by a MUTATION in the prion protein gene. In recent years a new variant of CJD has been identi?ed that is caused by BOVINE SPONGIFORM ENCEPHALOPATHY (BSE), called variant CJD. The incubation period for the acquired varieties ranges from four years to 40 years, with an average of 10–15 years. The symptoms of CJD are dementia, seizures, focal signs in the central nervous system, MYOCLONUS, and visual disturbances.

Abnormal prion proteins accumulate in the brain and the spinal cord, damaging neurones (see NEURON(E)) and producing small cavities. Diagnosis can be made by tonsil (see TONSILS) biopsy, although work is under way to develop a diagnostic blood test. Abnormal prion proteins are unusually resistant to inactivation by chemicals, heat, X-RAYS or ULTRAVIOLET RAYS (UVR). They are resistant to cellular degradation and can convert normal prion proteins into abnormal forms. Human prion diseases, along with scrapie in sheep and BSE in cattle, belong to a group of disorders known as transmissible spongiform encephalopathies. Abnormal prion proteins can transfer from one animal species to another, and variant CJD has occurred as a result of consumption of meat from cattle infected with BSE.

From 1995 to 1999, a scienti?c study of tonsils and appendixes removed at operation suggested that the prevalence of prion carriage may be as high as 120 per million. It is not known what percentage of these might go on to develop disease.

One precaution is that, since 2003, all surgical instruments used in brain biopsies have had to be quarantined and disposable instruments are now used in tonsillectomy.

Measures have also been introduced to reduce the risk of transmission of CJD from transfusion of blood products.

In the past, CJD has also been acquired from intramuscular injections of human cadaveric pituitary-derived growth hormone and corneal transplantation.

The most common form of CJD remains the sporadic variety, although the eventual incidence of variant CJD may not be known for many years.... creutzfeldt-jakob disease (cjd)

One of the blood proteins that maintains the balance between the blood clotting too easily or too slowly after an injury.

About 5 per cent of the population have an inherited mutation in the gene controlling factor V production, known as factor V Leiden.

They are at increased risk of deep-vein thrombosis (see thrombophilia), particularly if they are taking the oral contraceptive pill or go on long aircraft journeys.... factor v

Genes found in every cell that control growth, repair, and replacement.

Abnormalities of oncogenes are known to be a factor in the development of cancerous cells.

Mutations in oncogenes, resulting from damage by carcinogens, can cause a cell to grow unrestrainedly and infiltrate and destroy normal tissues (see cancer).

Factors known to cause cancer include ultraviolet light, radioactivity, tobacco, alcohol, asbestos, some chemicals, and certain viruses.... oncogenes

Known colloquially as ‘mad cow disease’, this is a fatal and untreatable disease. Along with scrapie in sheep and CREUTZFELDT-JACOB DISEASE (CJD) in humans, BSE belongs to a class of unusual degenerative diseases of the brain known as transmissible spongiform encephalopathies. The disease is caused by abnormal PRION proteins, which are resistant to cellular degradation. These abnormal prion proteins accumulate in and eventually cause the death of nerve cells, both in the spinal cord and the brain. The rare human disease CJD occurs throughout the world and is of three types: sporadic, iatrogenic (see IATROGENIC DISEASE) and inherited.

Since the BSE epidemic in cattle developed in the UK in the 1980s, however, a new variant of CJD has been identi?ed and is believed to be the result of consumption of the meat of BSE-infected cattle. Studies in transgenic mice have con?rmed that BSE caused variant CJD. The new variant has affected younger people and may have a shorter incubation period. If this incubation period turns out to be the same as for the other types of CJD, however, it could be 2005– 2010 before the peak of this outbreak is reached. Over 148 people had died, or were dying, from variant CJD in the UK by the year 2005.

The appearance of BSE in cattle is believed to have been caused by a gene mutation (see GENETIC DISORDERS), although whether this mutation ?rst occurred in cattle or in some other animal remains uncertain. Although the ?rst case of BSE was o?cially reported in 1985, the ?rst cattle are thought to have been infected in the 1970s. BSE spread to epidemic proportions because cattle were fed meat and bone meal, made from the o?al of cattle suffering from or incubating the disease. Mother-to-calf transfer is another likely route of transmission, although meat and bone meal in cattle feed were the main cause of the epidemic. The epidemic reached its peak in 1992 when the incidence of newly diagnosed cases in cattle was 37,545.

A two-year UK government inquiry into the BSE epidemic concluded that BSE had caused a ‘harrowing fatal disease in humans’, and criticised o?cials for misleading the public over the risk to humans from BSE. Consequently, a compensation package for patients and relatives was made available. Meanwhile, a ban on the export of UK beef and restrictions on the type of meat and products made from beef that can be sold to the public were put in place. Although initially thought to be a problem primarily con?ned to the UK, several other countries – notably France, Germany, Spain, Switzerland and the United States – have also discovered BSE in their cattle.... encephalopathy (bse)

The science of how the activity of DNA (deoxyribonucleic acid, which is the fundamental genetic material of cells) can be altered semi-permanently by chemical processes rather than by natural MUTATION. Genes contain instructions for making proteins. The natural process of implementing these instructions – gene expression – can be altered by chemical groups attaching themselves to the chemical bases that make up a strand of DNA. This, in turn, affects the generation of proteins from the genes so tagged. Some chemical groups can even stop a gene from being expressed. Recently, research in Australia showed that such a chemically induced alteration could be inherited, at least in mice. This points to the possibility that inherited epigenetic characteristics could cause ‘inherited diseases’ in the same way that natural genetic mutations do. These developments suggest that epigenetics will be an important part of genetic studies and research. Not all geneticists, however, believe that this developing aspect of genetics is so important and this debate will continue.... epigenetics

Genetic engineering, or recombinant DNA technology, has only developed in the past decade or so; it is the process of changing the genetic material of a cell (see CELLS). GENES from one cell – for example, a human cell – can be inserted into another cell, usually a bacterium, and made to function. It is now possible to insert the gene responsible for the production of human INSULIN, human GROWTH HORMONE and INTERFERON from a human cell into a bacterium. Segments of DNA for insertion can be prepared by breaking long chains into smaller pieces by the use of restriction enzymes. The segments are then inserted into the affecting organism by using PLASMIDS and bacteriophages (see BACTERIOPHAGE). Plasmids are small packets of DNA that are found within bacteria and can be passed from one bacterium to another.

Already genetic engineering is contributing to easing the problems of diagnosis. DNA analysis and production of MONOCLONAL ANTIBODIES are other applications of genetic engineering. Genetic engineering has signi?cantly contributed to horticulture and agriculture with certain characteristics of one organism or variant of a species being transfected (a method of gene transfer) into another. This has given rise to higher-yield crops and to alteration in colouring and size in produce. Genetic engineering is also contributing to our knowledge of how human genes function, as these can be transfected into mice and other animals which can then act as models for genetic therapy. Studying the effects of inherited mutations derived from human DNA in these animal models is thus a very important and much faster way of learning about human disease.

Genetic engineering is a scienti?c procedure that could have profound implications for the human race. Manipulating heredity would be an unwelcome activity under the control of maverick scientists, politicians or others in positions of power.... genetic engineering

n. a substance that can either reduce the spontaneous production of mutations or prevent or reverse the action of a *mutagen.... antimutagen

n. any of a class of proteins that function as transmembrane water channels. Genetic mutations of aquaporin 2 (AQP-2) are responsible for some distinct forms of *nephrogenic diabetes insipidus.... aquaporin

n. a strain of a microorganism, derived by mutation, that requires one or more specific factors for growth not needed by the parent organism.... auxotroph

irregular painless contractions of the uterus that occur during pregnancy and may become stronger towards term. [J. Braxton Hicks (1825–97), British obstetrician]

BRCA1 and BRCA2 genes associated with susceptibility to breast and ovarian cancer. Women with mutations in either of these genes have a 56–85% risk of developing breast cancer, and this form of the cancer tends to develop at a relatively young age. The risk of ovarian cancer is 36–66% in women with BRCA1 mutations and 10–20% with BRCA2. Targeted therapy specific to these mutations using a *PARP inhibitor is undergoing investigation.... braxton hicks contractions

Gyokuro tea is said to be the finest type of green tea. It is largely consumed for its health properties, but also for its unique taste. Its ingredients balance the diet in a harmonious way. Gyokuro tea description Gyokuro tea, or in translation “Jewel Dew”, is a fine type of green tea. It has a deep green colour and a rich seaweed and mellow taste flavor. Itscomponentsare theanine, caffeine, tannin and vitamin C. Theanine provides the tea’s flavor, caffeine its bitterness, and tannin its astringency. Gyokuro tea’s high quality and price are related to the unusual growing techniques. The tea is made only with the earliest leaf buds of the April/May harvest. The aforementioned tea is grown under shade cover for 20 days before harvesting begins. It is considered the best of the Japanese teas and offers consumers a refreshing experience. How to prepare Gyokuro tea Gyokuro tea is advisable to be drunk alone, without mixing it with milk or sugar. Occasionally, one can only serve it with a piece of dark chocolate. It seems that its leaves can be eaten, being soft and healthy.

• Use good quality water to prepare a good Gyokuro tea
• The optimal brewing temperature is between 122 F and 140 F degrees.
• First, preheat the cups or the teapot, because pouring the moderately warm tea into a cold cup changes its temperature.
• Pour some of the boiled water into the tea kettle and wait one or two minutes.
• Add the leaves and the remaining water.
• Use 2 table spoons of tea to approx. 4-5 ounces of water.
• Brewing time is between two and three minutes. While brewing, don’t mix, stir or shake the tea. Try to leave enough room for the leaves to expand.

Gyokuro tea benefits Due to its high content of antioxidants, Gyokuro tea reduces the risk of cancer. It can fight the free radicals responsible for the growth of tumors. This type of tea has a large contribution in making cells less likely to be affected by mutations. There have been instances in which it helped to cell recovery. Gyokuro tea can be successfully used to:

• stimulate the metabolism
• burn off  calories
• lower cholesterol
• protect against various cardiovascular diseases
• soothe and relax the mind
• enhance cognition and alertness
• improve concentration
• keep one energetic
• prevent dental plaque, bacterial infections and dental decay
• freshen your breathe
• protect against bacteria

Gyokuro tea side effects In case of large intakes of Gyokuro tea, insomnia may appear, especially to consumers already suffering from a sleep pattern disorder. Agitation and anxiety are other side effects caused by the content of caffeine. Children, people with heart medical problems and pregnant women are normally told to avoid Gyokuro tea or to drink it in limited quantities. Gyokuro tea contains a great quantity of antioxidants and caffeine that better people’s daily activities by enhancing their state of mind and well-being.  ... gyokuro tea health benefits

An inherited disorder of blood COAGULATION which results in prolonged bleeding even after minor injury. There is a de?ciency of factor VIII, an essential clotting factor in the coagulation cascade – the complex series of biochemical events that leads from injury of the wall of a blood vessel to the formation of a blood clot that checks bleeding. Haemophilia is a sex-linked recessive disorder (though a small number of cases arise by spontaneous mutation), so that, if females carry the disease, one-half of their sons will be affected and one-half of their daughters will be carriers. The sons of haemophiliacs are unaffected but one-half of their daughters will be carriers.

Haemophilia affects approximately 1:4,000 of the UK population but only 1:20,000 is severely affected. Severity of the disease depends upon the percentage, compared with normal, of factor VIII activity present. Less than 1 per cent and there will be spontaneous bleeding into joints and muscles; 1–5 per cent and there will be occasional spontaneous bleeding and severe bleeding after minor injury; 5–25 per cent and there will only be severe bleeding after major injury. Before treatment was available, severe haemophiliacs suffered from acute pain and deformity from bleeds into joints and muscles. Bleeding also occurred into the gut, kidneys and brain, and few survived past adolescence.

Freeze-dried factor VIII may be kept in domestic refrigerators. Haemophiliacs can use it to abort minor bleeds by reconstituting it and injecting it intravenously. More major bleeding or preparation for surgery involves raising factor VIII levels to 30–100 per cent by giving cryoprecipitate.

With treatment, most haemophiliacs lead normal lives, although obviously dangerous or contact sports should be avoided. Before donors of blood were screened for HEPATITIS B and C or for HIV infection (see AIDS/HIV), some individuals with haemophilia receiving factor VIII were unwittingly infected with those diseases. Today’s screening procedures make such infections very unlikely.

There is a National Haemophilia Register and each registered sufferer carries a card with details about his or her condition. Information may also be obtained from NHS haemophilia centres and the Haemophilia Society.... haemophilia

n. the evolution of an invasive cancer cell from a normal cell. This is a multistep process characterized by successive genetic mutations caused by carcinogens. Intermediate stages, sometimes called premalignant, preinvasive, or noninvasive, may be recognizable, but the interchangeable use of these terms can be confusing, and they have been replaced by *carcinoma in situ.... carcinogenesis

n. an inherited condition predisposing to arrhythmia that is characterized by a genetic mutation affecting one of the cell membrane channels responsible for transport of ions (e.g. potassium or sodium) into or out of the cardiac cells.... channelopathy

(deficiency) n. (in genetics) a type of mutation involving the loss of DNA. The deletion may be small, affecting only a portion of a single gene, or large, resulting in loss of a part of a chromosome and affecting many genes.... deletion

a rare disorder consisting of the triad of *nephroblastoma (Wilms’ tumour), congenital nephropathy, and intersex disorders, resulting from mutations in the Wilm’s tumour suppressor gene (WT1). Incomplete forms exist; congenital nephropathy, with diffuse mesangial sclerosis, is the constant feature with either Wilms’ tumour or intersex disorders, usually in the form of male *pseudohermaphroditism. [P. Denys (20th century), French physician; A. Drash (20th century), British physician]... denys–drash syndrome

The daily requirement of iron for an adult is 12 mg, and 15–20 mg for an adult woman during pregnancy. This is well covered by an ordinary diet, so that by itself it is not a common cause. But if there is a steady loss of blood, as a result of heavy menstrual loss or ‘bleeding piles’, the intake of iron in the diet may not be su?cient to maintain adequate formation of haemoglobin.

Symptoms These depend upon whether the anaemia is sudden in onset, as in severe haemorrhage, or gradual. In all cases, however, the striking sign is pallor, the depth of which depends upon the severity of the anaemia. The colour of the skin may be misleading, except in cases due to severe haemorrhage, as the skin of many Caucasian people is normally pale. The best guide is the colour of the internal lining of the eyelid. When the onset of the anaemia is sudden, the patient complains of weakness and giddiness, and loses consciousness if he or she tries to stand or sit up. The breathing is rapid and distressed, the pulse is rapid and the blood pressure is low. In chronic cases the tongue is often sore (GLOSSITIS), and the nails of the ?ngers may be brittle and concave instead of convex (koilonychia). In some cases, particularly in women, the Plummer-Vinson syndrome is present: this consists of di?culty in swallowing and may be accompanied by huskiness; in these cases glossitis is also present. There may be slight enlargement of the SPLEEN, and there is usually some diminution in gastric acidity.

CHANGES IN THE BLOOD The characteristic change is a diminution in both the haemoglobin and the red cell content of the blood. There is a relatively greater fall in the haemoglobin than in the red cell count. If the blood is examined under a microscope, the red cells are seen to be paler and smaller than normal. These small red cells are known as microcytes.

Treatment consists primarily of giving suf?cient iron by mouth to restore, and then maintain, a normal blood picture. The main iron preparation now used is ferrous sulphate, 200 mg, thrice daily after meals. When the blood picture has become normal, the dosage is gradually reduced. A preparation of iron is available which can be given intravenously, but this is only used in cases which do not respond to iron given by mouth, or in cases in which it is essential to obtain a quick response.

If, of course, there is haemorrhage, this must be arrested, and if the loss of blood has been severe it may be necessary to give a blood transfusion (see TRANSFUSION – Transfusion of blood). Care must be taken to ensure that the patient is having an adequate diet. If there is any underlying metabolic, oncological, toxic or infective condition, this, of course, must be adequately treated after appropriate investigations.

Megaloblastic hyperchromic anaemia There are various forms of anaemia of this type, such as those due to nutritional de?ciencies, but the most important is that known as pernicious anaemia.

PERNICIOUS ANAEMIA An autoimmune disease in which sensitised lymphocytes (see LYMPHOCYTE) destroy the PARIETAL cells of the stomach. These cells normally produce INTRINSIC FACTOR, the carrier protein for vitamin B12 (see APPENDIX 5: VITAMINS) that permits its absorption in the terminal part of the ILEUM. Lack of the factor prevents vitamin B12 absorption and this causes macrocytic (or megaloblastic) anaemia. The disorder can affect men and women, usually those over the age of 40; onset is insidious so it may be well advanced before medical advice is sought. The skin and MUCOSA become pale, the tongue is smooth and atrophic and is accompanied by CHEILOSIS. Peripheral NEUROPATHY is often present, resulting in PARAESTHESIA and numbness and sometimes ATAXIA. A rare complication is subacute combined degeneration of the SPINAL CORD.

In 1926 two Americans, G R Minot and W P Murphy, discovered that pernicious anaemia, a previously fatal condition, responded to treatment with liver which provides the absent intrinsic factor. Normal development requires a substance known as extrinsic factor, and this depends on the presence of intrinsic factor for its absorption from the gut. The disease is characterised in the blood by abnormally large red cells (macrocytes) which vary in shape and size, while the number of white cells (LEUCOCYTES) diminishes. A key diagnostic ?nd is the presence of cells in the BONE MARROW.

Treatment consists of injections of vitamin B12 in the form of hydroxocobalamin which must be continued for life.

Aplastic anaemia is a disease in which the red blood corpuscles are very greatly reduced, and in which no attempt appears to be made in the bone marrow towards their regeneration. It is more accurately called hypoplastic anaemia as the degree of impairment of bone-marrow function is rarely complete. The cause in many cases is not known, but in rather less than half the cases the condition is due to some toxic substance, such as benzol or certain drugs, or ionising radiations. The patient becomes very pale, with a tendency to haemorrhages under the skin and mucous membranes, and the temperature may at times be raised. The red blood corpuscles diminish steadily in numbers. Treatment consists primarily of regular blood transfusions. Although the disease is often fatal, the outlook has improved in recent years: around 25 per cent of patients recover when adequately treated, and others survive for several years. In severe cases promising results are being reported from the use of bone-marrow transplantation.

Haemolytic anaemia results from the excessive destruction, or HAEMOLYSIS, of the red blood cells. This may be the result of undue fragility of the red blood cells, when the condition is known as congenital haemolytic anaemia, or of acholuric JAUNDICE.

Sickle-cell anaemia A form of anaemia characteristically found in people of African descent, so-called because of the sickle shape of the red blood cells. It is caused by the presence of the abnormal HAEMOGLOBIN, haemoglobin S, due to AMINO ACID substitutions in their polypeptide chains, re?ecting a genetic mutation. Deoxygenation of haemoglobin S leads to sickling, which increases the blood viscosity and tends to obstruct ?ow, thereby increasing the sickling of other cells. THROMBOSIS and areas of tissue INFARCTION may follow, causing severe pain, swelling and tenderness. The resulting sickle cells are more fragile than normal red blood cells, and have a shorter life span, hence the anaemia. Advice is obtainable from the Sickle Cell Society.... inadequate intake of iron

a variety of mechanisms that help to ensure that the genetic sequence, as expressed in the DNA, is maintained and that errors that occur during DNA replication, by mutation, are not allowed to accumulate. An error in the genetic sequence could cause cell death by interfering with the replication process. DNA repair involves the action of enzymes, which detect damage to DNA and effect the repair. Some genetic diseases, including *ataxia telangiectasia and *xeroderma pigmentosum, are due to deficiencies in these enzymes.... dna repair

Leukaemia is an umbrella term for several malignant disorders of white blood cells in which they proliferate in a disorganised manner. The disease is also characterised by enlargement of the SPLEEN, changes in the BONE MARROW, and by enlargement of the LYMPH glands all over the body. The condition may be either acute or chronic.

According to the type of cells that predominate, leukaemia may be classi?ed as acute or chronic lymphoblastic leukaemia or myeloid leukaemia. Acute lymphoblastic leukaemia (ALL) is mostly a disease of childhood and is rare after the age of 25. Acute myeloid leukaemia is most common in children and young adults, but may occur at any age. Chronic lymphatic leukaemia occurs at any age between 35 and 80, most commonly in the 60s, and is twice as common in men as in women. Chronic myeloid leukaemia is rare before the age of 25, and most common between the ages of 30 and 65; men and women are equally affected. Around 2,500 patients with acute leukaemia are diagnosed in the United Kingdom, with a similar number annually diagnosed with chronic leukaemia.

Cause Both types of acute leukaemia seem to arise from a MUTATION in a single white cell. The genetically changed cell then goes through an uncontrolled succession of divisions resulting in many millions of abnormal white cells in the blood, bone marrow and other tissues. Possible causes are virus infection, chemical exposure, radiation and genetic background. The cause of chronic lymphocytic leukaemia is not known; the chronic myeloid version may have a genetic background.

Symptoms In acute cases the patient is pale due to anaemia, may have a purpuric rash due to lack of platelets, and may have enlarged lymphatic glands and spleen. The temperature is raised, and the condition may be mistaken for an acute infection (or may ?rst become apparent because the patient develops a severe infection due to a lack of normal white blood cells).

In the chronic type of the disease the onset is gradual, and the ?rst symptoms which occasion discomfort are either swelling of the abdomen and shortness of breath, due to painless enlargement of the spleen; or the enlargement of glands in the neck, armpits and elsewhere; or the pallor, palpitation, and other symptoms of anaemia which often accompany leukaemia. Occasional bleeding from the nose, stomach, gums or bowels may occur, and may be severe. Generally, there is a slight fever.

When the blood is examined microscopically, not only is there an enormous increase in the number of white cells, which may be multiplied 30- or 60-fold, but various immature forms are also found. In the lymphatic form of the disease, most white cells resemble lymphocytes, which, in healthy blood, are present only in small numbers. In the myeloid form, myelocytes, or large immature cells from the bone marrow, which are never present in healthy blood, appear in large numbers, and there may also be large numbers of immature, nucleated erythrocytes.

Treatment This varies according to the type of leukaemia and to the particular condition of the patient. Excellent results are being obtained in the control of ALL using blood transfusions, CHEMOTHERAPY, RADIOTHERAPY and bone-marrow TRANSPLANTATION. In the case of acute leukaemia, the drugs now being used include MERCAPTOPURINE, METHOTREXATE and CYCLOPHOSPHAMIDE. Blood transfusion and CORTICOSTEROIDS play an important part in controlling the condition during the period before a response to chemotherapy can be expected. Chemotherapy has almost completely replaced radiotherapy in the treatment of chronic leukaemia. For the myeloid form, BUSULFAN is the most widely used drug, replaced by hydroxyurea, mercaptopurine, or one of the nitrogen mustard (see NITROGEN MUSTARDS) derivatives in the later stages of the disease. For the lymphatic form, the drugs used are CHLORAMBUCIL, CYCLOPHOSPHAMIDE, and the nitrogen mustard derivatives.

Prognosis Although there is still no guaranteed cure, the outlook in both acute and chronic leukaemia has greatly improved – particularly for the acute form of the disease. Between 70 and 80 per cent of children with acute lymphoblastic leukaemia may be cured; between 20 and 50 per cent of those with acute myeloid leukaemia now have much-improved survival rates. Prognosis of patients with chronic lymphocytic leukaemia is often good, depending on early diagnosis.... leukaemia

(myotonic dystrophy) a type of *muscular dystrophy in which the muscle weakness and wasting is accompanied by an unnatural prolongation of the muscular contraction after any voluntary effort (see myotonia). The muscles of the face, temples, and neck are especially wasted. Baldness, endocrine malfunction, and cataracts also occur. The disease can affect both sexes (it is inherited as an autosomal *dominant disorder). Genetic testing for mutations in the dystrophia myotonica protein kinase gene is possible.... dystrophia myotonica

an inherited mutation in the gene coding for coagulation Factor V, which results in an increased susceptibility to develop venous *thrombosis.... factor v leiden

an autosomal *dominant disorder due to a mutation in the gene for the *prion protein (PrP): it is an example of a *spongiform encephalopathy. Patients present with intractable progressive insomnia, disturbances of the autonomic nervous system, and eventually dementia.... fatal familial insomnia

n. a filament-associated protein vital for skin barrier function. Mutations in the filaggrin gene have been associated with atopic *eczema, other atopic disease, and *ichthyosis vulgaris.... filaggrin

Energy in the form of waves or particles. Radiation is mainly electromagnetic and is broadly classi?ed as ionising and non-ionising. The former can propel ions from an atom; these have an electrical charge and can combine chemically with each other. Ionisation occurring in molecules that have a key function in living tissue can cause biological damage which may affect existing tissue or cause mutations in the GENES of germ-cell nuclei (see GAMETE; CELLS). Non-ionising radiation agitates the constituent atoms of nuclei but is insu?ciently powerful to produce ions.

Ionising radiation comprises X-RAYS, GAMMA RAYS and particle radiation. X-rays are part of the continuous electromagnetic-wave spectrum: this also includes gamma rays, infra-red radiation, ultraviolet light and visible light. They have a very short wavelength and very high frequency, and their ability to penetrate matter depends upon the electrical energy generating them. X-rays that are generated by 100,000 volts can pass through body tissue and are used to produce images – popularly known as X-rays. X-rays, generated at several million volts can destroy tissue and are used in RADIOTHERAPY for killing cancer cells. Gamma rays are similar to X-rays but are produced by the decay of radioactive materials. Particle radiation, which can be produced electrically or by radioactive decay, comprises parts of atoms which have mass as well as (usually) an electrical charge.

Non-ionising radiation includes ultraviolet light, radio waves, magnetic ?elds and ULTRASOUND. Magnetic ?elds are used in magnetic resonance imaging (MRI) and ultrasound, which is inaudible high-frequency sound waves, and is used for both diagnoses and treatment in medicine.... radiation

White tea is one of the most subtle and delicate of all varieties of tea. Discover the unique features of a well known type of white tea - Snow bud tea and learn more about its benefits. About Snow bud tea Snow bud tea belongs to the family of white teas which is one of the softest types of tea. Coming from Fujian province of China, this tea is delicious and fascinating, most appreciated by tea lovers. From each bush, only the finest tea leaves are used, with a minimal amount of processing. Tea buds and leaves are harvested in early spring before opening, when they are still covered with white hair. After that they are left in natural sunlight for whitening and drying. Also called Xue Ya, Snow bud tea is an airy, light tea with a subtle, gentle taste. It has a very delicate body, with an effervescent texture. Its transparent infusion has a flavor similar to toasted grains or baked sweet potatoes. The color of this tea can be similar to both green or white tea, but mostly it is light yellow. How to brew Snow bud tea When preparing the Snow bud tea, spring water would be most suitable, in order to avoid impurities. Remember to never boil the water, as it will ruin the taste of infusion. The ideal temperature for this tea ranges from 70ºC to 80ºC (approx. 160ºF to 175ºF). Infuse it for approximately 5 minutes and enjoy the rich taste. Because it is a quite expensive tea assortment, you can brew it more than once using the same leaves. This will also lower the caffeine content and will result in a mellow, gentle taste. Benefits of Snow bud tea Chinese people believe that Snow bud tea is refreshing and it has even cooling and detoxifying properties. Recent studies have demonstrated that, compared to other types of tea, this one has one of the highest concentration of catechins, almost three times bigger than green tea. Lack of fermentation process, Snow bud tea has also more polyphenols, believed to be a possible anti-cancer agent. This tea is low on caffeine, so, due to this, the possible side effects are quite rare. Studies have shown that this tea has a strong effect in halting cell mutation in an early stage of cancer, thus it successfully fights many types of cancer. The Snow bud tea is also excellent for hydrating the body and skin, having a natural anti-aging effect. It also boosts the metabolism, making you burn fat faster. So it is ideal for diets. Snow bud tea may help in fighting viruses and bacterial growth, reduce infections, pneumonia and even dental plaque, thus strengthening the whole immune system of your body. Let’s not forget about its anti-inflammatory and antioxidant effect. It also improves cardiovascular function. Side effects of Sun bud tea As far as the side effects, there are no identified ones when drinking Snow bud tea, except few related to low caffeine content. People with intolerance to caffeine, should, however, avoid drinking it at night. Snow bud tea is best for those who prefer green tea but want to experience the benefits of white tea. The long list of health benefits and the lack of side effects makes it ideal for daily consumption. So enjoy a relaxing cup of tea.... snow bud tea

(fluorescence in situ hybridization) a technique that allows the nuclear DNA of *interphase cells or the DNA of *metaphase chromosomes, which are fixed to a glass microscope slide, to anneal with a fluorescent gene *probe. It is used for detecting and locating gene mutations and chromosome abnormalities.... fish

the code in which genetic information is carried by *DNA and *messenger RNA. This information determines the sequence of amino acids in every protein and thereby controls the nature of all proteins made by the cell. The genetic code is expressed by the sequence of *nucleotide bases in the nucleic acid molecule, a unit of three consecutive bases (a codon) coding for each amino acid. The code is translated into protein at the ribosomes (see transcription; translation). Any changes in the genetic code result in the insertion of incorrect amino acids in a protein chain, giving a *mutation.... genetic code

an autosomal *dominant condition that is caused by a mutation in the *prion protein gene and resembles *Creutzfeldt-Jakob disease (CJD). Patients present with cerebellar dysfunction (*ataxia and *dysarthria) and later develop dementia. They continue to deteriorate over several years, in contrast with patients with CJD, who deteriorate rapidly over periods of less than 12 months. [J. G. Gerstmann]... gerstmann–straussler–scheinker syndrome

(HNPCC, Lynch syndrome) an inherited disorder in which there is an increased incidence of colorectal *polyp formation, although to a lesser extent than in familial adenomatous *polyposis (FAP). HNPCC has also been associated with other types of tumour, particularly ovarian and endometrial tumours. This increased risk is due to inherited mutations that impair DNA mismatch repair.... hereditary nonpolyposis colorectal cancer

Precursor of Vitamin A. Increases resistance against infection. Antioxidant. Together with Vitamins C and E form a vital line of defence in protection of strands of DNA, the genetic code, from cancerous mutation. Immune booster. Increases lymphocytes and T cells, part of the defence system.

Deficiency. Sun sensitivity; exposure inducing itching, burning and swelling of the skin. Kidney, bladder, and gut infections. Severe earache in young children. Strokes, heart attacks.

It is claimed that those who eat a diet rich in beta-carotene are less likely to develop certain types of cancer.

Smokers usually have low levels of beta-carotene in the blood. Statistics suggest that people who eat a lot of beta-carotene foods are less likely to develop lung, mouth or stomach cancer. In existing cases a slow-down of the disease is possible.

Daily dose. Up to 300mg. Excess may manifest as yellow discoloration of the skin, giving appearance of sun-tan.

Sources. Mature ripe carrots of good colour. A Finland study suggests that four small carrots contain sufficient beta-carotene to satisfy the recommended daily amount of Vitamin A. Orange and dark green fruits and vegetables. Broccoli, Brussels sprouts, spinach, pumpkin, apricots, peaches, oranges, tomatoes. Harvard Medical School study. Among 333 subjects with a history of heart disease, those who received beta-carotene supplements of 50 milligrams every other day suffered half as many heart attacks as those taking placebos. (Dr Charles Hennekens, Harvard Medical School) ... beta-carotene

Hazards from radiation may arise from external sources of radiation or from radioactive materials taken into the body. The effects depend on the dose, the duration of exposure, and the organs exposed.

With some forms of radiation, damage occurs when the radiation dose exceeds a certain limit, usually 1 sievert (Sv) (see radiation unit). This damage may include radiation dermatitis, cataracts, organ failure (which may occur many years later), or radiation sickness.

For other types of radiation damage, the risk that damage will occur increases with increasing doses of radiation. Cancer caused by radiation-induced mutation is the major example of this type of damage. Radioactive leaks from nuclear reactors can cause a rise in mutation rates, which may lead to an increase in cancers, such as leukaemias; to birth defects; and to hereditary diseases. Cancer usually develops years after exposure. Radiation damage can be controlled by limiting exposure. People exposed to radiation at work have their exposure closely monitored to ensure that it does not exceed safe limits. People of reproductive age or younger should have their reproductive organs shielded when having X-rays or radiotherapy.There is no evidence of radiation hazards with visual display units (VDUs).... radiation hazards

a group of rare inherited disorders characterized by recurrent attacks of fever and inflammation in the absence of infection. They include familial Mediterranean fever (see polyserositis), tumour necrosis factor receptor-associated periodic syndrome (TRAPS), and the cryopyrin-associated periodic syndrome (CAPS). Causative gene mutations have been identified.... hereditary periodic fever syndromes

n. excessive secretion of androgen in women. It is associated with *hirsutism, acne, sparse or infrequent menstruation (oligomenorrhoea), absent or infrequent ovulation, infertility, endometrial *hyperplasia, *hyperlipidaemia, *hyperglycaemia, and hypertension; all these conditions may be the result of mutations in specific genes. See also virilization.... hyperandrogenism

an inherited immunodeficiency syndrome characterized by normal or high IgM levels with absence of IgA, IgG, and IgE (see immunoglobulin). Patients are susceptible to bacterial and opportunistic infections. Some cases are due to a mutation in the gene encoding the CD40 ligand, which is synthesized by *helper T cells and is involved in activation of B cells to produce circulating antibodies.... hyper-igm syndrome

n. 1. the turning inwards or inside-out of a part or organ: commonly applied to the state of the uterus after childbirth when its upper part is pulled through the cervical canal. 2. a chromosome mutation in which a block of genes within a chromosome are in reverse order, due to that section of the chromosome becoming inverted. The centromere may be included in the inverted segment (pericentric inversion) or not (paracentric inversion).... inversion

the most common form of *dementia, occurring in middle age or later. It is characterized by memory impairment and, as the disease progresses, language difficulties, *apraxia, and visuospatial problems, leading to a loss of judgment and the inability to carry out even basic functions. At post mortem there are excess deposits of *amyloid protein and *neurofibrillary tangles in the brain. In rare cases of familial Alzheimer’s, mutations in three genes have so far been detected; patients with these genes usually have early-onset dementia. The cause of the common sporadic form is not known although genetic factors can significantly increase the risk of developing the disease. Mutations in four other genes have been implicated in the more common late-onset form of the disease. The demonstration of damage to the cholinergic pathways has led to the development of *acetylcholinesterase inhibitors, which have been shown to slow disease progression. Ethical problems in the care of someone who has been used to making their own decisions (but now cannot) include respecting what *autonomy remains, how to gain valid *consent for treatment, and how to allow the patient proper *dignity. [A. Alzheimer (1864–1915), German physician]

AMA see American Medical Association.... alzheimer’s disease

a malignant tumour of the breast, usually a *carcinoma, rarely a *sarcoma. It is unusual in men but is the most common form of cancer in women, in some cases involving both breasts. Cumulative exposure to higher oestrogen levels is implicated as a causal factor: breast cancer is most strongly associated with early menarche and late menopause, childlessness, and late age at the birth of the first child, and hence with an increase in the total number of menstrual cycles in a woman’s life. Approximately 5% of cases are due to the *BRCA1 and BRCA2 gene mutations.

The classic sign is a lump in the breast, usually painless; bleeding or discharge from the nipple may occur infrequently. Sometimes the first thing to be noticed is a lump in the axilla (armpit), which is caused by spread of the cancer to the drainage lymph nodes. The tumour may also spread to the bones, lungs, and liver. Current treatment of a localized tumour is usually by surgery (see lumpectomy; mastectomy), with or without radiotherapy; cytotoxic drugs and hormone therapy are used as *adjuvant therapy and *neoadjuvant chemotherapy and for widespread (metastatic) disease. Anti-oestrogenic agents used include *tamoxifen and (more recently) *aromatase inhibitors and *trastuzumab (Herceptin).... breast cancer

n. any *malignant tumour, including *carcinoma, *lymphoma, *leukaemia, and *sarcoma. It arises from the abnormal, purposeless, and uncontrolled division of cells that then invade and destroy the surrounding tissues. Spread of cancer cells (*metastasis) may occur via the bloodstream or the lymphatic channels or across body cavities such as the pleural and peritoneal spaces (see transcoelomic spread), thus setting up secondary tumours (metastases) at sites distant from the original tumour. Each individual primary tumour has its own pattern of local behaviour and spread; for example, bone metastasis is very common in cancers of the breast, bronchus, thyroid, kidney, and prostate but less common in other tumours.

There are many causative factors, some of which are known; for example, cigarette smoking is associated with lung cancer, radiation with some sarcomas and leukaemia, and several viruses are implicated (see oncogenic). A genetic element is implicated in the development of many cancers. In many cancers a gene called *p53 is deleted or impaired: its normal function is to prevent the uncontrolled division of cells (see tumour necrosis factor). Whatever the initiating cause, cancer always results ultimately from DNA mutations.

Treatment of cancer depends on the type of tumour, the site of the primary tumour, and the extent of spread. *Truth-telling will be important for most cancer patients but is still hard for some clinicians.... cancer

a family of autosomal *recessive genetic disorders causing decreased activity of any of the enzymes involved in the synthesis of *cortisol from *cholesterol. The most commonly affected enzymes are 21-hydroxylase and 11-hydroxylase, and each enzyme deficiency can itself be due to a variety of genetic mutations. The clinical manifestations depend on which enzyme is affected and the resultant deficiencies and build-up products produced. The most serious consequence is adrenal crisis and/or severe salt wasting due to lack of cortisol and/or aldosterone, which may prove fatal if undiagnosed. The condition is often easier to spot at birth in females, who may have indeterminate genitalia due to high levels of *testosterone in utero. Adrenal hyperplasia occurs due to excessive stimulation of the glands by *ACTH (adrenocorticotrophic hormone) in response to the resultant cortisol deficiency of these conditions. Less complete deficiencies of the enzymes concerned may present for the first time in young women after puberty, with signs of androgen excess and menstrual irregularity mimicking *polycystic ovary syndrome.... congenital adrenal hyperplasia

n. a condition caused by *mast cell proliferation due to KIT *proto-oncogene mutations. It most commonly manifests in the skin but also affects other organs. Maculopapular variants were formerly known as urticaria pigmentosa. Systemic involvement is common in adult cases, with bone marrow examination essential for accurate diagnosis. It may be associated with haematological abnormalities, including leukaemias. Resolution is common in children with skin involvement only. Treatment includes antihistamines, mast-cell stabilizers (such as sodium *cromoglicate), and *tyrosine kinase inhibitors.... mastocytosis

(MODY, monogenic diabetes) a range of rare but important forms of type 2 *diabetes mellitus caused by a single autosomal *dominant genetic defect. The two commonest forms are mutations of the HNF-1? gene (MODY 3), which often responds to treatment with *sulphonylurea drugs, and mutations of the glucokinase gene (MODY 2), causing a mild elevation of blood glucose levels usually responsive to dietary management.... maturity-onset diabetes of the young

adj. affected by or showing the effects of a mutation. —mutant n.... mutant

a rare X-linked (see sex-linked) recessive inherited condition usually presenting in childhood or early adult life with polyuria, microscopic haematuria, renal stone disease, or rickets. The majority of patients have a mutation of the gene encoding chloride channel 5 (CLCN5); others have a defect of the OCRL1 gene, normally associated with Lowe’s syndrome, but do not present with the cataracts, learning disability, and tubular acidosis associated with this condition. In still others the genetic defect has yet to be defined but is not associated with either CLCN5 or OCRL1. Patients with Dent’s disease have evidence of proximal tubular dysfunction. [C. E. Dent (1911–76), British physician]... dent’s disease

dimercaptosuccinic acid, which when labelled with *technetium-99m is used as a tracer to obtain *scintigrams of the kidney, by means of a *gamma camera. DMSA binds to the proximal tubules of the kidney. It is used particularly to show renal scarring, resulting from infection, and to assess the relative quantity of functioning tissue in each kidney.

DNA (deoxyribonucleic acid) the genetic material of nearly all living organisms, which controls heredity and is located in the cell nucleus (see chromosome; gene). DNA is a *nucleic acid composed of two strands made up of units called *nucleotides (see illustration). The two strands are wound around each other into a double helix and linked together by hydrogen bonds between the bases of the nucleotides (see base pairing). The genetic information of the DNA is contained in the sequence of bases along the molecule (see genetic code); changes in the DNA cause *mutations. The DNA molecule can make exact copies of itself by the process of *replication, thereby passing on the genetic information to the daughter cells when the cell divides.... dmsa

a major genetic disorder caused by a constriction near the end of the long arm of an *X chromosome: it is inherited as an X-linked *dominant characteristic. The fragile-X syndrome is second only to *Down’s syndrome as a cause of learning disability. Affected males have unusually high foreheads, unbalanced faces, large jaws, long protruding ears, and large testicles. They have an IQ below 50 and are prone to violent outbursts. Folic acid helps to control their behaviour. About one-third of the females with this mutation on one of their two X chromosomes also show developmental delay. Screening for the characteristic chromosome can be done by *amniocentesis or *chorionic villus sampling.... fragile-x syndrome

(hereditary haemochromatosis, bronze diabetes, iron-storage disease) n. a hereditary disorder in which there is excessive absorption and storage of iron. This leads to damage and functional impairment of many organs, including the liver, pancreas, and endocrine glands. The main features are a bronze colour of the skin, diabetes, and liver failure. It is inherited as an autosomal *recessive trait in people of northern European descent and is due to mutations in the haemochromatosis gene (HFE) in the majority of cases. Iron may be removed from the body by blood letting or an iron *chelating agent may be administered. Compare haemosiderosis.... haemochromatosis

n. the presence of elevated concentrations of *cholesterol in the blood (see also hyperlipidaemia), which predisposes to atheromatous disease (see atheroma). Familial hypercholesterolaemia is an autosomal *dominant condition in which raised levels of *low-density lipoprotein (LDL) result from a mutation in the LDL receptor gene, producing a deficiency of LDL receptors, which normally remove cholesterol from the circulation. The *heterozygous state, with LDL levels of 5–10 mmol/1, may not be detected until adulthood; usual signs are tendon *xanthomas on the backs of the hands and a *corneal arcus. The *homozygous state is much more serious as cardiovascular complications can occur in childhood, due to massively increased total cholesterol levels (>12 mmol/1).... hypercholesterolaemia

a rare autosomal *dominant condition characterized by hypertension associated with hypokalaemia, metabolic alkalosis, and low levels of plasma *renin and *aldosterone. The hypertension often starts in infancy and is due to excess resorption of sodium and excretion of potassium by the renal tubules. The syndrome is caused by a single genetic mutation on chromosome 16, which results in dysregulation of a sodium channel in the distal convoluted tubule. Treatment is with a low salt diet and a potassium-sparing diuretic that directly blocks the sodium channel, such as amiloride or triamterene. [G. G. Liddle (1921–89), US endocrinologist]... liddle’s syndrome

n. a gene in viruses (v-onc) and mammalian cells (c-onc) that can cause cancer. It results from the mutation of a normal gene (a *proto-oncogene). An oncogene is capable of both initiation and continuation of malignant transformation of normal cells. It probably produces proteins (*growth factors) regulating cell division that, under certain conditions, become uncontrolled and may transform a normal cell to a malignant state.... oncogene

(hereditary haemorrhagic telangiectasia) a hereditary (autosomal *dominant) disorder characterized by thinning of the blood vessel walls, resulting in abnormally wide and fragile blood vessels. Patients may develop telangiectasia (see telangiectasis), nosebleeds, and arteriovenous malformations (see angioma). It is caused by mutations in the endoglin (ENG) gene or the activin receptor-like kinase (ALK-1) gene. [Sir W. Osler (1849–1919), Canadian physician; H. J. M. Rendu (1844–1902), French physician; F. P. Weber (1863–1962), British physician]... osler–rendu–weber disease

a rare disorder in which prolonged contraction of muscle fibres (see myotonia) is precipitated by cold and exercise. It is due to a mutation in the sodium-channel gene.... paramyotonia congenita

a group of muscle diseases, marked by weakness and wasting of selected muscles, in which there is a recognizable pattern of inheritance. The affected muscle fibres degenerate and are replaced by fatty tissue. The muscular dystrophies are classified according to the patient’s age at onset, distribution of the weakness, the progression of the disease, and the mode of inheritance. Isolated cases may occur as a result of gene mutation. Confirmation of the diagnosis is based upon *electromyography and muscle biopsy.

One common form is Duchenne’s muscular dystrophy, which is inherited as a *sex-linked recessive character and is nearly always restricted to boys. It usually begins before the age of four, with selective weakness and wasting of the muscles of the pelvic girdle and back. The child has a waddling gait and *lordosis of the lumbar spine. The calf muscles – and later the shoulders and upper limbs – often become firm and bulky. Although the disease cannot be cured, physiotherapy and orthopaedic measures can relieve the disability. The identification of the gene abnormality raises the possibility of *gene therapy in the future. See also Becker muscular dystrophy; dystrophia myotonica.... muscular dystrophy

(NDI) a condition characterized by *polyuria and *polydipsia and due to failure of the renal tubules to respond, or to respond fully, to *vasopressin. One form of congenital NDI is caused by an X-linked (see sex-linked) dominant mutation of the gene encoding the vasopressin V2 receptor. A rarer form of congenital NDI is an autosomal recessive condition associated with genetic mutations in the gene encoding AQP-2 water channels (see aquaporin). Acquired NDI is much commoner than the congenital form and usually less severe. It is present in most patients with advancing chronic renal failure, is a feature of certain electrolyte disorders (hypokalaemia, hypercalcaemia), and can complicate chronic lithium treatment.... nephrogenic diabetes insipidus

a drug that blocks the action of the PARP enzyme, which is required for *DNA repair in cancer cells with faulty *BRCA1 and BRCA2 genes. These drugs are used in the treatment of cancer in patients with BRCA1 or BRCA2 mutations. They are also undergoing trials to see if they are useful in the treatment of other cancers.... parp inhibitor

n. the study of how genes affect the actions of drugs. The enormous growth of knowledge about the human genome, arising from the *Human Genome Project, has revolutionized drug treatment, enabling the precise targeting of drugs against the products of specific mutations causing disease (see targeted agent). In addition, it will be possible to identify those genetic variations that affect how drugs are metabolized in the body and their potential for causing adverse effects. Thus analysis of genetic data from individuals will enable safer and more effective treatment.... pharmacogenomics

n. a situation in which a single gene is responsible for more than one effect in the *phenotype. The mutation of such a gene will therefore have multiple effects. —pleiotropic adj.... pleiotropy

either of two inherited disorders in which renal cysts are a common feature. Autosomal recessive polycystic kidney disease (ARPKD) occurs in about 1 in 20,000 live births. It is due to a single mutation on chromosome 6 for the gene encoding the protein fibrocystin. The majority of cases are diagnosed before or at birth. The most severely affected fetuses have enlarged kidneys and *oligohydramnios due to poor fetal renal output. These fetuses develop the ‘Potter’ phenotype with characteristic facies, pulmonary hypoplasia, and deformities of the spine and limbs. Those surviving the neonatal period (50–70%) develop varying degrees of renal impairment but this may not proceed to end-stage until early adulthood.

Autosomal dominant polycystic kidney disease (ADPKD) affects between 1 in 400 and 1 in 1000 individuals and is one of the most common hereditary diseases. Two types have been defined. ADPKD 1 is the commonest and responsible for about 85% of cases. It is due to a mutation in the PKD1 gene on chromosome 16, which encodes polycystin 1, an *ion-channel-regulating protein. ADPKD2 is due to a mutation in the PKD2 gene on chromosome 4, which encodes the protein polycystin 2, a calcium-release channel. ADPKD2 tends to be a milder disease with later presentation.

ADPKD is a multisystem disorder that is also associated with cyst formation in other organs (particularly the liver), cardiovascular disorders, and colonic diverticular disease. Renal disease presents in early adult life with haematuria, loin pain, urinary tract infection, hypertension, renal stone disease, or the finding of a mass in the abdomen. Other cases are identified by family contact tracing; the findings of a few cysts on renal ultrasonography in a young adult with a family history of ADPKD is highly suggestive of the disease. Renal disease is progressive and about 50% of patients will have reached end-stage by the time they enter their seventh decade. The progress of the renal failure can be slowed by good blood pressure control. In the UK, patients with ADPKD are responsible for 5–10% of the total on renal replacement therapy.

There are a number of separate rare autosomal dominant conditions other than ADPKD1 and ADPKD 2 that can present with polycystic kidneys. These include *von Hippel-Lindau disease and *tuberous sclerosis.... polycystic disease of the kidneys

menopause occurring before the age of 40. It may be caused by autoimmunity, chemotherapy, radiotherapy, or genetic factors, for example a mutation in the FSH receptor gene causing excess secretion of gonadotrophins and small underdeveloped ovaries. Treatment is by hormone replacement, either with the contraceptive pill or HRT. *Oocyte donation should be discussed if the patient wishes for assisted conception.... premature ovarian failure

n. an inherited or acquired condition that predisposes individuals to *thrombosis. Inherited thrombophilias are established causes of systemic thrombosis due to defects in proteins involved in regulating *blood coagulation. Causes include *Factor V Leiden gene mutation, a *prothrombin gene mutation, deficiencies in proteins C and S and antithrombin III, and hyperhomocysteinaemia (see homocysteine). —thrombophilic adj.... thrombophilia

a rare *sex-linked recessive disorder characterized by eczema, *thrombocytopenia, and deficiency in the immune response (*immunodeficiency). It is caused by a decrease in the amount of Wiskott–Aldrich syndrome protein (WASP: a protein occurring in lymphocytes, platelets, and other cells) due to a mutation in the WASP gene.... wiskott–aldrich syndrome