Selected inherited disorders
Various inherited disorders are summarized in Table 81.1.
Table 81.1
| Disorder | Main feature |
| Acute intermittent porphyria | The porphyrias are disorders of haem biosynthesis. The acute porphyrias which present with abdominal pain and neurological features all have increased urinary porphobilinogen during an attack, and this is diagnostic |
| Adrenoleucodystrophy | This rare neurodegenerative disease is characterized by the impaired metabolism and subsequent accumulation of long chain fatty acids in plasma and tissues, and adrenal insufficiency |
| Agammaglobulinaemia | There is a complete absence of immunoglobulin production. Selective IgA deficiency is more common with affected children presenting with recurrent respiratory infections |
| Alpha-1-antitrypsin deficiency | Patients with deficiency of the protease inhibitor, alpha-1-antitrypsin, may present with liver disease in childhood or with pulmonary emphysema in adults. All patients with genotypes associated with low alpha-1-antitrypsin in the serum are likely to develop emphysema if they smoke or are exposed to environmental pollutants |
| Biotinidase deficiency | A failure of biotin recycling results in an organic aciduria, developmental delay, seizures, alopecia, hypotonia and hearing loss |
| Congenital adrenal hyperplasia | This name is given to disorders of the enzymes involved in steroid hormone biosynthesis. The most common is lack of the 21-hydroxylase on the pathways which lead to cortisol and aldosterone synthesis (pp. 94–95) |
| Cystic fibrosis | This autosomal recessive condition is relatively common, being encountered in 1/1600 Caucasian births. Around 1/22 of the population are carriers, making this disease one of the most common serious genetic abnormalities. It is caused by a defective protein called cystic fibrosis transmembrane conductance regulator (CFTR), which regulates the function of a bicarbonate/chloride exchanger. |
| Cystinuria | An increased excretion of the dibasic amino acids cystine, lysine, arginine and ornithine leads to an increased incidence of renal calculi. A defective carrier protein causes impaired renal tubular reabsorption of these amino acids from the glomerular filtrate |
| Cystinosis | This is a lysosomal storage disorder where there is a defect in the membrane transport of cystine. Cystine crystals are deposited in kidney, liver, spleen, bone marrow and cornea |
| Familial hypercholesterolaemia | See pages 134–135 |
| Galactosaemia | This defect is present in approximately 1 : 100 000 babies in the UK. A deficiency of galactose 1-phosphate uridyl transferase means that the baby cannot utilize the galactose component of the lactose which is present in milk. Such infants may present with failure to thrive, vomiting and diarrhoea and if untreated may die in the neonatal period or go on to develop liver disease, mental retardation, cataracts and renal tubular damage. |
| Glucose-6-phosphate dehydrogenase deficiency | This is an X-linked disorder associated with neonatal jaundice on the 2nd or 3rd day of life and drug-induced haemolytic crises |
| Glycogen storage disease (type I: von Gierke’s) | Deficiency of glucose-6-phosphatase makes the glycogen stores of the body inaccessible. Children with this disorder have hepatomegaly and hypoglycaemia accompanied by hyperlipidaemia and lactic acidosis |
| Haemochromatosis | See pages 114–115 |
| Homocystinuria | A deficiency of the enzyme cystathionine synthase leads to the accumulation of sulphur-containing amino acids. Affected children are normal at birth but develop eye problems, osteoporosis and mental retardation |
| Lesch–Nyhan syndrome | This is a severe form of hypoxanthine–guanine phosphoribosyltransferase deficiency, an enzyme involved in the metabolism of the purine bases (pp. 144–145) resulting in delayed motor development, bizarre sinuous movements and self-mutilation |
| Maple syrup urine disease | This defect in the decarboxylation of branched chain amino acids such as leucine, isoleucine and valine leads to severe brain damage and death during the first year of life |
| Mucopolysaccharidoses | This group of disorders is characterized by tissue accumulation of glycosaminoglycans such as heparin sulphate and dermatan sulphate. This results in skeletal deformities, mental retardation and premature death |
| Multiple endocrine neoplasias | See pages 142–143 |
| Muscular dystrophy | See pages 146–147 |
| Phenylketonuria | See pages 156–157 |
| Propionic acidaemia | This is caused by deficiency of enzymes involved in the metabolism of propionyl coenzyme A |
| Urea cycle defects | Deficiency of enzymes of the urea cycle results in a build-up of ammonia in the blood. Severe cases are often fatal in the first few days after birth. |
| Vitamin D dependent rickets | See pages 76–77 |
| Wilson’s disease | This causes variable neurological and hepatic symptoms as a consequence of copper toxicity (pp. 116–117). |
