Israel Medical Association Journal

Background: Transthyretin (TTR)-associated familial amyloid polyneuropathy (FAP) is an autosomal dominant multisystem disease with neurological and extra-neurological manifestations. It is caused by various mutations in the TTR gene leading to the formation of insoluble amyloid.

Objectives: To describe the clinical and genetic findings 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.  
 

Background: Myotonic dystrophy type 2 (DM2) is an autosomal dominant, multisystem disorder caused by a CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene) on chromosome 3q 21.3.

Objectives: To describe the clinical, electrophysiologic and pathologic findings in patients with myotonic dystrophy 2.

Methods: We evaluated 10 patients genetically, clinically and electrophysiologically during the years 2007 to 2008.

Results: All patients were of Jewish European ancestry. Among affected individuals, eight patients had symptoms of proximal muscle weakness, two had muscle pain, and two exhibited myotonia. On physical examination six patients had severe weakness of hip flexor muscles. Seven individuals underwent cataract surgery, and cardiac involvement was seen in one case. On the initial electromyographic (EMG) examination five patients demonstrated myotonic discharges; repeated studies showed these discharges in nine cases. Six muscle biopsies showed non-specific pathological changes. Seven patients had an affected first-degree relative with either a diagnosed or an undiagnosed muscular disorder, consistent with an autosomal dominant trait.

Conclusions: DM2 may often present with proximal muscle weakness without myotonia. EMG may initially fail to show myotonic discharges, but these discharges may eventually show in most cases on repeated EMG. Thus, DM2 may be underdiagnosed and should be included in the differential diagnosis of adult patients of Jewish European ancestry presenting with proximal lower limb weakness.