Acute intermittent porphyria (AIP) is a hereditary disease characterized biochemically by a defect in the heme pathway enzyme porphobilinogen deaminase. There is wide variability in the neurologic clinical expression of AIP, and the disorder remains latent in most gene carriers. The natural history of the disease and results in a porphyric rat model sugget a significant relationship between tryptophan metabolites and clinical expression of the disease. In the present study, we examined urine and blood tryptophan metabolite levels in AIP women before, during and after acute attacks and treatment by heme arginate. Heme arginate treatment promptly decreased total tryptophan levels (from 69 ± 9, to 44 ± 5, mean ± SEM, μmole/l, p < 0.001), serotonin blood levels (from 629 ± 103, to 356 ± 80, nmole/l, p < 0.01) and the urinary excretion of 5-HIAA (from 3.9 ± 0.6, to 2.2 ± 0.4, μmole/mmole creatinine, p < 0.01). The plasma level of melatonin was found much lower than the normal control level at night (86.2 ± 70.3, vs the normal range, 409 ± 78.9, pmole/l ± SEM) and day time (38.8 ± 22.0, vs 75 ± 13.7). Heme arginate treatment did not influence melatonin levels. Our results support the involvement of abnormal tryptophan metabolism in the pathophysiology of AIP acute attacks. Low melatonin plasma levels in porphyric women suggest that the defect of the pineal hormone may be responsible for the recurrent aspect of porphyric attacks. A desynchronization of biological rhythms in AIP patients may increase the inducibility of hepatic ALA synthase to environmental risk factors and, specially, to sex steroid hormones.
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- Yves NORDMANN, Centre Français des Porphyries, Hôpital Louis Mourier, 92701 Colombes, France.
Copyright © 1993 Published by Elsevier Inc.