Abstract
Summary:δ-Aminolevulinic acid dehydratase (ALAD) deficiency porphyria, or Doss porphyria, was first reported in Germany in 1979. Only four bona fide cases of Doss porphyria have been reported to date that were confirmed by immunological and molecular analyses of their ALAD mutations. Here we describe the fifth case of Doss porphyria. A 17-year-old German male suffered from colicky abdominal pain and severe polyneuropathy for 2 years. Urinary δ-aminolevulinic acid (ALA) was increased 32-fold, and coproporphyrin 76-fold compared with the upper limit of their respective normal ranges. Urinary excretion of porphobilinogen (PBG) and uroporphyrin was only slightly increased. Faecal porphyrins were within the normal range. Erythrocyte zinc protoporphyrin concentrations were elevated 5.4-fold. ALAD activity in erythrocytes was decreased to 10% of the normal value, and was not activated by zinc and by dithiothreitol. Blood lead levels were within the normal range, excluding lead poisoning in the proband. Erythrocyte ALAD activity was about one-half of the normal value in both parents, whereas it was normal in the proband's brother. Urinary excretion of ALA, PBG and total porphyrins was within the normal range in both parents and the brother. Molecular genetic studies of the ALAD gene in the proband revealed two base changes, C to A and C to T, both in intron 3 at -11 bp upstream of the exon 3 start site. In addition to the proband, the father carried the -11C-to-T, while the mother carried the ALAD gene in the proband's brother. These findings suggest that the observed compound heterozygosity of the ALAD gene may be responsible for Doss porphyria in the proband. The proband was successfully treated with haem arginate infusion. The clinical condition improved, and urinary excretion of ALA and coproporphyrin fell to levels of ~50% compared with their pretreatment levels during acute relapses. The haem therapy was continued once weekly for 1 year. At the end of 1 year, urinary ALA and porphyrin levels were significantly lowered, and the proband is now almost free of clinical symptoms.
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Doss, M.O., Stauch, T., Gross, U. et al. The third case of Doss porphyria (δ-amino-levulinic acid dehydratase deficiency) in Germany. J Inherit Metab Dis 27, 529–536 (2004). https://doi.org/10.1023/B:BOLI.0000037341.21975.9d
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DOI: https://doi.org/10.1023/B:BOLI.0000037341.21975.9d