Chapter 17 Disorders of haemoproteins, porphyrins and iron
Haemoproteins
Porphyrins
The porphyrias
The porphyrias are classified as acute or non-acute, according to their clinical presentation, and hepatic or erythropoietic, depending on the major site of abnormal metabolism (Fig. 17.3). All the porphyrias are rare. Cutaneous hepatic porphyria (also known as porphyria cutanea tarda) is the most common but many cases are not inherited. Of the purely genetic types, acute intermittent porphyria is the most common, with a prevalence in the UK, where it occurs more frequently than in many countries, of 1–2 cases per 100 000 of the population. Unusually for inherited metabolic diseases, the mode of inheritance of most porphyrias is autosomal dominant, the exceptions being congenital erythropoietic porphyria, ALA dehydratase deficiency porphyria and hepatoerythropoietic porphyria (autosomal recessive). The features of the porphyrias are summarized in Figure 17.4. The genes for the enzymes involved in porphyrin synthesis have been identified and cloned, but the porphyrias are genetically heterogeneous; this hinders the application of molecular biological techniques to the identification of carriers and to screening for porphyrias.
Acute porphyrias
Clinical features
These conditions are characterized by a tendency to acute attacks, separated by long periods of complete remission. The clinical features of acute attacks are summarized in Figure 17.5. Abdominal pain and psychiatric disturbances are nearly always present; peripheral neuropathy occurs in some 60% of patients. Attacks can be precipitated by various factors, including many drugs (see Fig. 17.5); most frequently implicated are barbiturates, oral contraceptives and alcohol. These probably act by increasing the activity of ALA synthase, in many cases by increasing the synthesis of hepatic cytochrome P450 and hence the demand for haem, thereby decreasing intrahepatic haem concentration and releasing the enzyme from inhibition. Some drugs, notably the sulphonamides, inhibit PBG deaminase directly. Whatever the cause, the resulting increased activity of the metabolic pathway increases the formation of metabolites before the enzyme block.
You may also need

Full access? Get Clinical Tree

