A novel G168X mutation and a recurrent 730-731delCT mutation of the porphobilinogen deaminase gene in Japanese patients with acute intermittent porphyria

摘要

Acute intermittent porphyria (AIP), an autosomal dominant disease, is caused by a deficiency of the third enzyme in heme-biosynthesis, porphobilinogen deaminase (PBGD) [1]. Patients with this disease present with a neurological syndrome which may take the form of autonomic or peripheral axonal neuropathy or central nervous system dysfunction. The symptoms are generally manifested intermittently with rapid onset, and can be induced by drugs, alcohol, starvation, infection, endocrine factors or excessive stress [1]. However, most carriers of the defective gene are clinically latent. Therefore, early detection of carriers of the defective gene is important to prevent the attack, since carriers can be advised to avoid the precipitating factors. Determination of the gene abnormality has been successfully made in many cases, and, to date, more than 300 mutations in the PBGD gene have been characterized (http://www.hgmd.cf.ac.uk). Recently, we established the diagnosis of AIP for two Japanese patients from separate families, and identified two pathogenic mutations in the PBGD gene.