TY - JOUR
T1 - Clinical and genetic findings in eight Israeli patients with Transthyretin-associated familial amyloid polyneuropathy
AU - Leibou, Lior
AU - Frand, Jacob
AU - Sadeh, Menachem
AU - Lossos, Alexander
AU - Kremer, Eyal
AU - Livneh, Avi
AU - Yarnitsky, David
AU - Herman, Oscar
AU - Dabby, Ron
PY - 2012
Y1 - 2012
N2 - Background: Transthyretin (TTR)-associated familial amyloid polyneuropathy (FAP) is an autosomal dominant multisystem disease with neurological and extra-neurological mani- festations. It is caused by various mutations in the TTR gene leading to the formation of insoluble amyloid. Objectives: To describe the clinical and genetic fndings in patients with TTR-associated FAP in Israel. methods: We evaluated eight patients clinically and genetically during the years 2006 to 2011. results: At onset, all the patients exhibited sensory loss of the lower and upper limbs, five patients experienced muscle pain, and one patient had lower limb weakness. Five patients had autonomic nervous system manifestations, and four demonstrated evidence of amyloid cardiomyopathy. Nerve conduction studies showed sensorimotor axonal neuropathy in all patients. Sural nerve biopsies were obtained in five patients; only three biopsies revealed amyloid deposit. In four patients of Yemenite descent, genetic analysis of the TTR gene demonstrated ser77tyr mutation. One patient of Tunisian descent and one Ashkenazi patient harbored the val30met mutation. One patient of Iranian descent showed val32ala mutation, and another Ashkenazi patient showed phe33leu mutation. conclusions: TTR-associated FAP is a progressive and fatal disease that exists in the Israeli population and is unproportionally common among Yemenite Jews. This disease may be under-diagnosed and should be considered in the differential diagnosis of any patient with rapidly progressive neuropathy, especially with autonomic involvement or extra-neural features. The absence of amyloid in nerve biopsy should not rule out the diagnosis.
AB - Background: Transthyretin (TTR)-associated familial amyloid polyneuropathy (FAP) is an autosomal dominant multisystem disease with neurological and extra-neurological mani- festations. It is caused by various mutations in the TTR gene leading to the formation of insoluble amyloid. Objectives: To describe the clinical and genetic fndings in patients with TTR-associated FAP in Israel. methods: We evaluated eight patients clinically and genetically during the years 2006 to 2011. results: At onset, all the patients exhibited sensory loss of the lower and upper limbs, five patients experienced muscle pain, and one patient had lower limb weakness. Five patients had autonomic nervous system manifestations, and four demonstrated evidence of amyloid cardiomyopathy. Nerve conduction studies showed sensorimotor axonal neuropathy in all patients. Sural nerve biopsies were obtained in five patients; only three biopsies revealed amyloid deposit. In four patients of Yemenite descent, genetic analysis of the TTR gene demonstrated ser77tyr mutation. One patient of Tunisian descent and one Ashkenazi patient harbored the val30met mutation. One patient of Iranian descent showed val32ala mutation, and another Ashkenazi patient showed phe33leu mutation. conclusions: TTR-associated FAP is a progressive and fatal disease that exists in the Israeli population and is unproportionally common among Yemenite Jews. This disease may be under-diagnosed and should be considered in the differential diagnosis of any patient with rapidly progressive neuropathy, especially with autonomic involvement or extra-neural features. The absence of amyloid in nerve biopsy should not rule out the diagnosis.
KW - Familial amyloid polyneuropathy
KW - Nerve biopsy
KW - Nerve conduction studies
KW - Neuropathy
KW - Transthyretin gene
UR - http://www.scopus.com/inward/record.url?scp=84870756380&partnerID=8YFLogxK
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AN - SCOPUS:84870756380
SN - 1565-1088
VL - 14
SP - 662
EP - 665
JO - Israel Medical Association Journal
JF - Israel Medical Association Journal
IS - 11
ER -