title: Acute intermittent porphyria: mutation analysis and identification of gene carriers in a German kindred by PCR-DGGE analysis.
abstract: Acute intermittent porphyria (AIP) is the most frequent acute porphyria. Symptomatic patients and asymptomatic gene carriers are characterized by a reduction of their porphobilinogen-deaminase (PBG-D) activity to 50%, which is sufficient for porphyrin biosynthesis. PBG-D is encoded by two different mRNAs which are expressed in a tissue-specific manner. In classical AIP, the enzyme activity is reduced in erythroblasts and all other heme-forming body cells, whereas in the variant form of AIP, the PBG-D activity in erythroid tissues remains normal. Acute porphyria attacks can occur in gene carriers when the biosynthesis of heme is increased by drugs, low calorie intake, alcohol consumption or infections. Under these conditions, PBG-D cannot convert the precursors adequately so that PBG and delta-aminolevulinate accumulate. This may lead to neurovisceral symptoms and other neurological complications which are potentially life threatening. In patients with AIP, mutation analysis by PCR-DGGE (denaturing gradient gel electrophoresis) is becoming increasingly important since it also permits rapid identification of their presymptomatic relatives. Using this technique, more than 120 mutations have been identified in the PBG-D gene. When identified, the family members are informed about their genetic predisposition and are taught how to prevent porphyric attacks. Here, I illustrate this preventive strategy by describing a German kindred of an affected patient with the variant form of AIP with 17 family members.
authors.affiliation: Department of Medicine II, Charité, Humboldt University, Berlin, Germany. petrides@charite.de
authors.forename: P E
authors.initials: PE
authors.lastname: Petrides
mesh_terms: D004586:Electrophoresis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000378:metabolism*; D007527:Isoenzymes; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D016133:Polymerase Chain Reaction; D017118:Porphyria, Acute Intermittent / Q000235:genetics / Q000517:prevention & control
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011163:Hydroxymethylbilane Synthase