Porphyrias in Japan

Abstract

Porphyrias are a clinically diverse group of diseases due to inherited deficiencies of enzymes in the heme biosynthetic pathway. Much progress has been made in the analysis of porphyrin metabolism, and the molecular biology of the enzymes in heme biosynthesis and their mutations in the porphyrias are now actively investigated. These diseases are classified into two types: erythropoietic and hepatic, depending on the major site of the clinical expression of the enzyme defect. They are further classified into eight subtypes according to the porphyrin metabolites that are over-produced and according to the causative enzyme defects. These diseases are all inherited as auto-soma1 dominant traits, except for congenital erythropoietic porphyria (CEP) and 6-aminolevulinic acid dehydratase (ALAD) deficiency porphyria (ADP), which are recessive. In addition, a few homozygous forms of the dominantly inherited porphyrias have also been recognized, which are presumably due to mutations with a milder enzymatic defect. The main clinical manifestations of the porphyrias are neurologic syndromes and skin photosensitivity.