The porphyrias

Abstract

The porphyrias are a remarkable family of metabolic disorders characterized biochemically by overproduction of haem precursors, principally in the liver and bone marrow. The acute porphyrias are inborn errors of varying penetrance that affect enzymatic steps in a tightly regulated biosynthetic pathway for haem; nonacute acquired forms also occur in genetically predisposed individuals. Clinical presentation of acute porphyria—life-threatening neurovisceral attacks occur in four of the porphyrias: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and Doss’ porphyria (5-aminolaevulinate dehydratase deficiency). These present with abdominal pain, psychiatric symptoms, and signs of sympathetic and hypothalamic autonomic overactivity, sometimes accompanied by convulsions and motor and sensory deficits. Diagnosis of acute porphyria—this is key to survival of an acute attack of porphyria, which can be suspected on the basis of the past history, in particular of photosensitivity or the intermittent discoloration of urine, and family history, and is confirmed by finding excess water-soluble haem precursors in urine. Management of acute porphyria—treatment of an acute porphyric attack mandates immediate withdrawal of inappropriate drugs and other precipitating factors; infusions of haem arginate or other licensed preparations of haem shorten life-threatening episodes and may be effective prophylaxis for recurrent porphyria in women with periodic attacks. The nonacute porphyrias are photosensitivity syndromes caused by excess photoactive macrocyclic porphyrins triggered especially by visible light in the blue–violet range. In the most severe form, manifestations are of severe blistering lesions on sun-exposed skin, particularly of the hands and face, with the formation of vesicles and bullae that may become infected. Healing may lead to loss of digits, scarring of the eyelids, nose, lips, and scalp, and occasionally blindness due to corneal scarring.