Galactosaemia Health Dictionary

A protein that acts as a catalyst for the body’s metabolic processes. The body contains thousands of enzymes, with each cell producing several varieties. The ?rst enzyme was obtained in a reasonably pure state in 1926. Since then, several hundred enzymes have been obtained in pure crystalline form. They are present in the digestive ?uids and in many of the tissues, and are capable of producing in small amounts the transformation on a large scale of various compounds. Examples of enzymes are found in the PTYALIN of saliva and DIASTASE of pancreatic juice which split up starch into sugar; the PEPSIN of the gastric juice and the trypsin of pancreatic juice which break proteins into simpler molecules and eventually into the constituent amino acids; and the thrombin of the blood which causes coagulation.

The diagnosis of certain disorders can be helped by measuring the concentrations of various enzymes in the blood. After a heart attack (myocardial infarction – see HEART, DISEASES OF), raised levels of heart enzymes occur as a result of damage to the cells of the heart muscle. Some inherited diseases such as GALACTOSAEMIA and PHENYLKETONURIA are the result of de?ciencies of certain enzymes.

Enzymes can be a useful part of treatment for some disorders. STREPTOKINASE, for example, is used to treat THROMBOSIS; wound-dressings containing papain from the pawpaw fruit – this contains protein-digesting enzymes – assist in the healing process; and pancreatic enzymes can be of value to patients with malabsorption caused by disorders of the PANCREAS.... enzyme

A constituent of lactose, galactose is a simple sugar that is changed in the liver to glucose. A rare genetic metabolic disease, GALACTOSAEMIA, results in infants being unable to achieve this conversion because the enzyme necessary for the reaction is absent.... galactose

A collection of disorders in which some part of the body’s internal chemistry (see METABOLISM; CATABOLISM) is disrupted. Some of these disorders arise from inherited de?ciencies in which a speci?c ENZYME is absent or abnormal, or does not function properly. Other metabolic disorders occur because of malfunctions in the endocrine system (see ENDOCRINE GLANDS). There may be over- or underproduction of a hormone involved in the control of metabolic activities: a prime example is DIABETES MELLITUS – a disorder of sugar metabolism; others include CUSHING’S SYNDROME; hypothyroidism and hyperthyroidism (see THYROID GLAND, DISEASES OF); and insulinoma (an insulin-producing tumour of the pancreas). The bones can be affected by metabolic disorders such as osteoporosis, osteomalacia (rickets) and Paget’s disease (see under BONE, DISORDERS OF). PORPHYRIAS, HYPERLIPIDAEMIA, HYPERCALCAEMIA and gout are other examples of disordered metabolism.

There are also more than 200 identi?ed disorders described as inborn errors of metabolism. Some cause few problems; others are serious threats to an individual’s life. Individual disorders are, fortunately, rare – probably one child in 10,000 or 100,000; overall these inborn errors affect around one child in 1,000. Examples include GALACTOSAEMIA, PHENYLKETONURIA, porphyrias, TAY SACHS DISEASE and varieties of mucopolysaccharidosis, HOMOCYSTINURIA and hereditary fructose (a type of sugar) intolerance.... metabolic disorders

Loss of transparency of the crystalline lens of the eye, due to changes in its delicate protein fibres. At an advanced stage, the front part of the lens becomes densely opaque, but the cataract never causes total blindness.

Almost everyone over 65 has some degree of cataract. Regular exposure to ultraviolet light increases the risk. Other causes include injury to the eye, particularly if a foreign body enters the lens. Cataract is common in people who have diabetes mellitus. Long-term use of corticosteroid drugs may contribute to cataract development. Congenital cataract may be due to an infection of the mother in early pregnancy, especially with rubella, to the toxic effects of certain drugs in pregnancy, or be associated with Down’s syndrome or galactosaemia.

Onset of symptoms is almost imperceptible, although night driving may be affected early on.

There is slow, progressive loss of visual acuity.

The person may become shortsighted and notice disturbances in colour perception.

When vision has become seriously impaired, cataract surgery is performed to remove the lens.... cataract

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

Spontaneous, persistent production of milk by a woman who is not pregnant or lactating (see lactation), or, very rarely, by a man.

Lactation is initiated by a rise in the level of prolactin, a hormone produced by the pituitary gland. Galactorrhoea is caused by excessive secretion of prolactin due to a pituitary tumour or otherendocrine disease, such as hypothyroidism. Some antipsychotic drugs may also cause excessive secretion. Treatment with bromocriptine suppresses prolactin production, but the underlying cause may also need treatment. galactosaemia A rare, inherited condition in which the body is unable to convert the sugar galactose into glucose due to the absence of a liver enzyme. It causes no symptoms at birth, but jaundice, diarrhoea, and vomiting soon develop and the baby fails to gain weight. Untreated, the condition results in liver disease, cataract, and learning difficulties. The diagnosis is confirmed by urine and blood tests. The major source of galactose is the milk sugar lactose. Lactosefree milk must be used throughout life. gallbladder A small, pear-shaped sac situated under the liver that stores bile. Bile, produced by the liver, passes into the gallbladder via the hepatic and cystic ducts. It is released into the intestine via the common bile duct.... galactorrhoea