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The Porphyrias

Acute Intermittent Porphyria

Three forms of porphyria occurring in South Africa may be associated with the acute attack. Variegate porphyria (See Variegate porphyria) is by far the commonest. A second form of porphyria, acute intermittent porphyria, is less frequently encountered but may be associated with life threatening acute attacks.

Enzyme Defect

The defective enzyme is porphobilinogen deaminase. This enzyme catalyses an early step in haem synthesis, and when defective, the porphyrin precursors ALA and PBG may accumulate. (See Introduction to porphyria.) Since accumulation of these precursors is associated with the acute attack, patients with acute intermittent porphyria are particularly prone to acute attacks. The porphyrins, which are photoactive, do not accumulate to a significant extent, and acute intermittent porphyria is therefore never complicated by skin disease.

Genetic Defect

The disease is inherited as an autosomal dominant trait. Both males and females are equally affected, and offspring of an affected parent have a 50% chance of inheriting the defect. (See Inheritance of porphyria.) More than 100 mutations associated with acute intermittent porphyria had been described throughout the world. South African families with acute intermittent porphyria are found in all population groups. In black South African families in particular, the diagnosis is often not suspected and therefore missed. Since no single mutation is predominant, genetic testing is of little use in diagnosis.

Clinical Defects

Acute intermittent porphyria may be complicated by the acute attack, which may be very severe. (See Acute symptoms in porphyria). Occasional patients with acute intermittent porphyria-—particularly young women-—suffer a problem of severe, recurrent acute attacks, some of which are cyclical and are related to the menstrual cycle (See Dealing with recurrent acute attacks of porphyria). Skin disease is never encountered in acute intermittent porphyria. Long-standing acute intermittent porphyria may be associated with the development of chronic hypertension and chronic renal failure in and beyond middle age.

Diagnosis

The diagnosis of acute intermittent porphyria is frequently delayed, since the disease is not suspected in patients who have no skin disease. In South African laboratories the diagnosis is made by the demonstration of elevated ALA and PBG concentrations in a urine sample, in the absence of diagnostic evidence for variegate porphyria in plasma and faecal samples (See Diagnosis of porphyria). These biochemical tests will detect clinically expressed patients, but have a low sensitivity for asymptomatic carriers, many of whom will have a normal urine PBG concentration. A more sensitive test is an enzyme assay demonstrating reduced erythrocyte PBG deaminase activity. This is not routinely offered in South Africa. A DNA-based genetic test is only suitable if the mutation carried within a particular family has been identified, in which case detection of the mutation is the most sensitive test for the screening of family members. DNA analysis for acute intermittent porphyria is not routinely offered in South Africa.

Therapy

Treatment is based on rapid and effective intervention for the acute attack (See Management of the acute attack).

Drug Precautions

Full drug precautions are necessary as patie