Stauch T.1, Renz M1., Seelig H. P1, Doss M.O.2
1Laboratory Prof. Seelig and Colleagues, Karlsruhe, 2Clinical Biochemistry, Consultation Porphyria, Philipps University, Marburg, Germany
Acute hepatic porphyrias (AHP) are characterized by a complex acute clinical syndrome in conjunction with excessive excretion of heme precursors in urine and/or feces, with enzyme deficiencies based on mutations in the corresponding genes of the heme biosynthetic pathway. We report on two male patients with an polysympto-matic manifestation of an acute porphyria syndrome which was first diagnosed as acute intermittent porphyria (AIP). In both cases porphyrin precursor ALA and PBG as well as porphyrin excretion was extremely elevated.
Case 1: A 23-year-old male patient was diagnosed as AIP due to high excretion of ALA (378 µmol/24h, normal <49), PBG (559 µmol/24 h, normal <8) and porphyrins (6878 µg/24 h, normal <145), Uro/Copro-ratio 4:1. Fecal porphyrins were normal. The activity of PBG-deaminase was 71% of controls. Molecular genetic analysis of the PBG deaminase gene (Intron/Exon 1–14) did not exhibit any mutation. Analogous investigations of the coproporphyrinogen oxidase and protoporphyrinogen oxidase genes did also show no deviations of the normal base sequence. The patient was treated successfully with heme arginate both by the acute and the interval application treatment type.
Case 2: A 12-year-old boy sufferd from severe neurological symptoms which were probably induced by antiepileptic drugs. He excreted high amounts of ALA (358 µmol/24h), PBG (311 µmol/24h) and porphyrins (4721 µg/24h), Uro/Copro-ratio 1:5. Urinary Copro III Isomer was 96% (normal 69-83%). Fecal porphyrins were normal (34 µg/g, normal <85) as well as the PBG deaminase activity (70%). Mutation analyses of PBG deaminase and protoporphyrinogen oxidase genes did not show any aberrations. However the sequence of the coproporphyrinogen oxidase gene shows in codon 272 of the exon 4 the transversion AAC>CAC leading to a substitution of the amino acid asparagine by histidine at this position. We think that this mutation can be interpreted most likely as a genetic polymorphism without effect on the enzyme activity. Nevertheless, the intense metabolic dysregulation enforces a weekly application of heme arginate. Under this therapy the excretion values returned to subclinical levels: ALA 77 µmol/24 h, PBG 95 µmol/24 h and porphyrins to 428 µg/24 h. In conclusion, these studies illustrate that a clear molecular genetic explanation of the porphyrias still remains difficult in some cases. Furthermore the value of genetic analyses should not be overestimated. These data do not serve for clinical explanation of the porphyria process. Also in the future the clinical biochemical analyses of the excretory constellations of porphyrin precursors and porphyrins remain of decisive importance for diagnostic and therapeutic purposes.