Clinical and histopathological features of familial amyloidotic polyneuropathy with transthyretin Val30Ala in a Chinese family

• Published in: Journal of the neurological sciences 2011-05, Vol.304 (1), p.83-86
• Main Authors: Liu, Jing-Yao, Guo, Ying-Jie, Zhou, Chun-Kui, Ye, Yu-Qin, Feng, Jun-Qiang, Yin, Fei, Jiang, Xin-Mei
• Format: Article
• Language: English
• Subjects: Adult; Alanine - genetics; Amyloid Neuropathies, Familial - diagnosis; Amyloid Neuropathies, Familial - genetics; Amyloidosis; Asian Continental Ancestry Group - genetics; Autopsy; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Familial amyloidotic polyneuropathy; Fatal Outcome; Female; Humans; Male; Medical sciences; Neurology; Pedigree; Point Mutation - genetics; Polymerase chain reaction (PCR); Polymorphism; Prealbumin - genetics; Transthyretin (TTR) gene; Valine - genetics
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2011.02.005

Abstract Familial amyloidotic polyneuropathy (FAP) is characterized by extracellular deposition of amyloid fibrils caused by a point mutation in the transthyretin ( TTR ) gene. TTR amyloidosis is linked to a vast number of mutations with varying phenotype and tissue distribution. Several Chinese kindred with FAP type 1 have been reported in Beijing, Hong Kong, Taiwan, and elsewhere. Here, histopathological features and TTR gene polymorphism were analyzed by using autopsy and blood specimens from a Chinese proband of a family with FAP. This proband is a 34-year old man with FAP type 1 who developed motor, sensory and autonomic impairments with neuropathy, gastrointestinal dysfunction, and orthostatic hypotension. Genetic findings of TTR revealed a T to C transition in codon 30 causing the mutation TTR Ala30. This patient died of respiratory and circulatory failure 7 years after onset. Autopsy showed heavy amyloid deposition in the peripheral nerves, liver, testes, thyroid, pancreas and muscles. There was moderate deposition in the heart, kidneys, bladder, gastrointestinal tract, tongue, lung, blood vessels, and gall bladder. The spleen showed only slight deposition, and none was observed in the central nervous system. TTR amyloidosis was confirmed by immunochemical staining with a specific TTR antibody. These results indicate that the distribution of amyloid deposition, (i.e., heavy in the liver, testes and slight in the spleen), is a characteristic feature and reflects the severity of FAP with TTR Val30Ala.