[Genetic analysis and a new therapy for a hereditary disease: familial amyloid polyneuropathy].

Familial amyloid polyneuropathy (FAP) is a hereditary disorder with autosomal dominant trait and is characterized by the accumulation of transthyretin at the nervous systems. The disorder mostly becomes overt in the fourth decade of life among affected individuals. Treatment of FAP has been directed toward the relief of symptoms and not intended to eliminate the yet unknown cause of this disorder. Recently, Val30 to Met substitution in the transthyretin gene was found among the patients with typical FAP. This enabled us to genotype affected individuals by PCR-RFLP and paved the way to the treatments directed to lower the levels of abnormal transthyretin in patients. In 1990, a Swedish group successfully performed liver transplantation to patients with FAP. This report was followed by more than 60 cases of liver transplantation to FAP patients in the Western hemisphere. Herein, I describe the first case of living-related liver transplantation to an FAP patient at Shinshu University Hospital. The patient was a 31-year-old female, whose father and aunt died of typical FAP in their fifth decade. She was suffering from severe pains in her lower extremities and nausea and vomiting. PCR-RFLP of her transthyretin gene revealed that she was heterozygous for Val to Met substitution at codon 30. In 1993, she was transplanted the left lobe of liver from her elder sister, who was genetically free of the disorder. Two weeks after the transplantation, serum Met30-transthyretin levels fell below 5% of the initial level. Symptoms due to peripheral nervous system and gastrointestinal tract were relieved after the transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)