Hereditary coproporphyria. Demonstration of the abnormalities in haem biosynthesis in peripheral blood
Brodie, M.J.; Thompson, G.G.; Moore, M.R.; Beattie, A.D.; Goldberg, A.
Quarterly Journal of Medicine 46(182): 229-241
1977
ISSN/ISBN: 0033-5622 PMID: 866576 Document Number: 110648
Hereditary coproporphyria is biochemically distinct from the other porphyrias and is characterized by excessive excretion of coproporphyrin in feces and usually in urine. The laboratory findings in 28 patients with this disease are presented and the clinical details of 8 patients who had an attack were summarized. The remaining 20 patients were latent for the disease. In all patients studied the activity of .delta.-aminolevulinic acid synthase was raised and coproporphyrinogen oxidase depressed in the leukocyte. This indicates the partial enzyme block in the heme biosynthetic pathway in this disease. The activities of the other enzymes in the pathway, leukocyte ferrochelatase and erythrocyte .delta.-aminolevulinic acid dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase, showed no consistent change. In review of 111 cases, 35% presented an acute attack: 80% had abdominal pain, 34% vomiting, 29% solar sensitivity, 23% neurological involvement, 23% psychiatric symptoms and 20% severe constipation. Only 2 fatalities were published, both from respiratory failure. There was a female preponderance of cases in attack of 2.5:1 and in the latent cases of 1.5:1 suggesting hormonal provocation in the uncovering of the disease. Drugs were implicated as precipitating 54% of acute attacks and in 34% of the cases, these were barbiturates. This study demonstrates the reduction in activity of coproporphyrinogen oxidase in the heme biosynthetic pathway and the elevation of .delta.-aminolevulinic acid synthase in the peripheral blood. These features, together with the typical abnormal porphyrin excretion pattern, appear to be diagnostic of hereditary coproporphyria whether in attack, remission or in the latent form.