Variegate porphyria is the most frequently encountered form of porphyria in South Africa, followed by porphyria cutanea tarda and acute intermittent porphyria. Erythropoietic protoporphyria is uncommon. Of the remaining forms of porphyria, two are encountered in South Africa but are very rare, whereas the third has not yet been reported in South Africa. These are described here.

Congenital Erythropoietic Porphyria

The enzyme defect is in the enzyme uroporphyrinogen cosynthase. This is an erythropoietic porphyria, and the enzyme defect is expressed in erythrocytes (See Introduction to porphyria). Patients develop severe photosensitivity in childhood (See Skin disease in porphyria). This is a mutilating condition. By adolescence and early adulthood, patients may lose their lips, pinnae of the ears, eyelids and noses, and develop severe hypertrichosis. Bones and teeth may be discoloured and will fluoresce under ultraviolet light. Associated manifestations of the defect in haemoglobin synthesis include a mild haemolytic anaemia and splenomegaly. Some have speculated that the "werewolves" of legend may have been based on unfortunate patients with this disorder, with hairy, scarred faces, deformed ears and noses, contracted lips exposing discoloured teeth in an apparent snarl, and who avoid daylight because of their photosensitivity. The disorder is diagnosed by demonstrating fluorescence of erythrocytes under ultraviolet light and by showing a characteristic accumulation of uroporphyrin and other hydroxylated porphyrins in urine and erythrocytes (See Diagnosis of porphyria). Treatment is difficult, and unsatisfactory, and may include avoidance of exposure to light and the use of oral sorbents such as activated charcoal to interrupt the enterohepatic cycling of porphyrins. Bone marrow transplantation has been used in the treatment of congenital erythropoietic porphyria and gene therapy is under investigation.

Hereditary Coproporphyria

The defective enzyme is coproporphyrinogen oxidase. There are a few families with this condition in South Africa. Clinically the disease resembles variegate porphyria in that patients are prone to both photocutaneous sensitivity (See Skin disease in porphyria) and to acute attacks (See Acute symptoms in porphyria). Diagnosis is by demonstration of a significantly elevated urine and stool coproporphyrin, but can be confused with variegate porphyria (See Diagnosis of porphyria). Treatment is symptomatic. Drug precautions (Drug prescription in patients with porphyria) must be followed in view of the potential to develop acute attacks.

ALA Dehydratase Deficiency Porphyria

This is also known as Doss porphyria or plumboporphyria. The defective enzyme is ALA dehydratase. The condition is extremely rare and only a handful of cases—none in South Africa—have been described. The condition is diagnosed by the demonstration of an elevated urine ALA in the presence of a normal PBG: this biochemical profile is seen is also in lead poisoning. Clinically the disease is marked by acute attacks in the absence of skin disease.

Homozygous Porphyrias

The common porphyrias, variegate porphyria, acute intermittent porphyria and the familial form of porphyria cutanea tarda are autosomal dominant conditions and patients with these disorders are heterozygous for the gene defect. Extremely rare instances of homozygotes or compound heterozygotes (See Inheritance of porphyria) have been described, and typically are very severely affected. In the homozygous forms of both acute intermittent porphyria and variegate porphyria, the clinical phenotype includes gross anatomical and neurodevelopmental abnormalities. Four cases of compound heterozygous variegate porphyria have been described in South Africa (See Homozygous variegate porphyria).