Paediatrics: Disorders of porphyrin metabolism

Disorders of porphyrin metabolism

The porphyrins are the main precursors of haem, and essential constit-uents of haemoglobin, myoglobin, the respiratory and P450 liver cyto-chromes, and of other enzymes (catalases and peroxidases). Deficiency in porphyrin pathway leads to accumulation of precursors, which are toxic to tissues in high concentration. The chemical properties of these precur-sors determines the site of tissue accumulation, and whether they induce photosensitivity.

The porphyrias (Table 26.3) may be inherited or acquired. They are broadly classified as hepatic porphyrias or erythropoietic porphyrias, based on the site of the overproduction and main accumulation of the porphyrins. They manifest with either skin problems or with neurological complications (or occasionally both) and present either acutely or non-acutely.

•   Hepatic porphyrias: are characterized by acute neurological attacks manifesting as seizures, neuropathy, behaviour problems/pyschosis, and hallucinations. Muscle (back) pain, vomiting, and abdominal pain are also common. Acute episodes may be triggered by exposure to certain drugs (e.g. alcohol, oral contraceptive agents, and certain antibiotics) and by other chemicals and certain foods. Fasting can also trigger attacks.

•   Erythropoietic porphyrias: present with skin problems, including light-sensitive blistering rash and increased hair growth.

Spectroscopic and biochemical analysis for abnormalities in porphyrin metabolite profile in urine and stools is required for diagnosis. In nearly all cases of acute porphyria syndromes, urinary porphobilinogen is markedly elevated (except in ALA dehydratase deficiency).

Treatment

Acute porphyria

High carboydrate diet and avoidance of precipitating factors. Haemearginate (early in acute episode). Symptomatic treatment.

Erythropoietic porphyrias

The skin rash that occurs in erythropoietic porphyrias generally requires use of sunscreens and avoidance of bright sunlight. Chloroquine may be used to increase porphyrin secretion.