Pe. Petrides, Acute intermittent porphyria: Mutation analysis and identification of genecarriers in a German kindred by PCR-DGGE analysis, SKIN PH APP, 11(6), 1998, pp. 374-380
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.