VARIEGATE PORPHYRIA IN SOUTH-AFRICA, 1688 - 1996 - NEW DEVELOPMENTS IN AN OLD DISEASE

Variegate porphyria, an autosomal dominant inherited trait resulting i n decreased activity of protoporphyrinogen oxidase, the penultimate ha em biosynthetic enzyme, is characterised clinically by photosensitive skin disease and a propensity to acute neurovisceral crises. The disea se has an exceptionally high frequency in South Africa, owing to a fou nder effect. The specific mutation in the protoporphyrinogen oxidase g ene sequence which represents this founder gene has been identified. G enetic diagnosis is therefore now possible in families in whom the gen e defect is known, However, the exact nature and degree of activity of the porphyria can only be determined by detailed quantitative biochem ical analysis of excreted porphyrins. The relative contributions of th e acute attack and the skin disease to the total disease burden of pat ients with variegate porphyria is not static, and in South Africa ther e have been significant changes over the past 25 years, with fewer pat ients presenting with acute attacks, leaving a greater proportion to p resent with skin disease or to remain asymptomatic with the diagnosis being made in the laboratory. The mast common precipitating cause of t he acute attack of VP is administration of porphyrinogenic drugs. Spec ific suppression of haem synthesis with intravenous haem arginate is t he most useful treatment of a moderate or severe acute attack, Althoug h cutaneous lesions are limited to the sun-exposed areas, management o f the skin disease of VP remains inadequate.