Doss M.O.1, Stauch T.2, Groß U.3, Renz M.2, Akagi R.4, Doss-Frank M.1, Seelig H.P.2, Sassa S.4
1Clinical Biochemistry, Consultation Porphyria, Philipps University, Marburg, Germany, 2Laboratory Prof. Seelig and Colleagues, Karlsruhe, Germany, 3Department of Neurosurgery, J. W. Goethe-University, Frankfurt am Main, Germany, 4The Rockefeller University, Laboratory of Biochemical Hematology, New York, USA
Delta-aminolevulinic acid (ALA) dehydratase (ALAD) deficiency porphyria (ADP), or Doss porphyria, has first been reported in Germany in 1979 (Klin. Wochenschr. 57: 1123; 1979). Two unrelated male adolescents suffered from severe, mainly neuropathic acute porphyria syndrome by nearly total ALAD deficiency. About seven cases of ADP have been reported to date, but only four cases have been confirmed by determination of the underlying ALAD mutation (Semin. Liver Dis. 18: 75; 1998). The molecular genetic studies confirmed that ADP is an autosomal recessive porphyria resulting from compound heterozygous mutations of the ALAD gene. A 17-year-old male suffered from colical abdominal pain and symptoms of severe polyneuropathy for two years. Due to an excessive porphyrinuria, porphyria was suspected and the patient was referred to our consultation. Urinary ALA was increased 33-fold, and coproporphyrin-III 79-fold. Porphobilinogen and uroporphyrin were only slightly increased. Fecal porphyrins were within the normal range. In erythrocytes zinc protoporphyrin was elevated 5-fold. ALAD activity in erythrocytes was decreased to 8% of normal controls and could not be activated by Zn and DTT, suggesting an ALAD protein deficiency. Blood lead levels were not elevated. ALAD activity was about 50% in both parents, whereas the patient's brother had normal activity. Urinary ALA and porphyrin excretion were within the normal range in both parents and the brother. Molecular genetic studies of the ALAD gene revealed two base changes in the family: 11C to A in intron 3 in the mother and 11C to T intron 3 in the father. No mutations were detected in his brother. Only the patient carried both mutations. These findings suggest that the observed compound heterozygosity of the ALAD gene may be responsible for Doss porphyria in the patient. The patient was treated several times by heme arginate. The clinical condition improved, and the excretion of ALA and coproporphyrin fell about 50% compared with the acute level. The heme therapy was continued intermittently for one year. Urinary parameters returned significantly to subclinical levels. The patient is currently in a good clinical condition. He is free of pain, and the polyneuropathy returned nearly to normal. [This study was supported by the German Research Association (GR 1363/2-3)].