Acute intermittent porphyria: Mutation analysis and identification of genecarriers in a German kindred by PCR-DGGE analysis

Acute intermittent porphyria (AIP) is the most frequent acute porphyria. Sy mptomatic patients and asymptomatic gene carriers are characterized by a re duction of their porphobilinogen-deaminase (PBG-D) activity to 50%, which i s sufficient for porphyrin biosynthesis. PBG-D is encoded by two different mRNAs which are expressed in a tissue-specific manner. In classical AIP, th e enzyme activity is reduced in erythroblasts and all other heme-forming bo dy cells, whereas in the variant form of AIP, the PBG-D activity in erythro id tissues remains normal. Acute porphyria attacks can occur in gene carrie rs when the biosynthesis of heme is increased by drugs, low calory intake, alcohol consumption or infections. Under these conditions, PBG-D cannot con vert the precursors adequately so that PEG and delta-aminolevulinate accumu late. This may lead to neurovisceral symptoms and other neurological compli cations which are potentially life threatening. In patients with AIP, mutat ion analysis by PCR-DGGE (denaturing gradient gel electrophoresis) is becom ing increasingly important since it also permits rapid identification of th eir presymptomatic relatives. Using this technique, more than 120 mutations have been identified in the PBG-D gene. When identified, the family member s are informed about their genetic predisposition and are taught how to pre vent porphyric attacks. Here, I illustrate this preventive strategy by desc ribing a German kindred of an affected patient with the variant form of AIP with 17 family members.