Neurologic Involvement in Val-122 Ile Familial Amyloidosis (P1.026)

OBJECTIVE: Describe new phenotype in familial amyloid cardiomyopathy. BACKGROUND: Late onset cardiomyopathy with heart failure is the phenotype of familial amyloidosis, which occurs in African Americans (AA) in the United States at a rate 4 times that of whites after the age of 60. 3.9% of AA are heterozygous for the amyloidogenic allele where isoleucine substitutes for valine at position 122 (Val- 122-Ile) of the serum carrier protein transthyretin (TTR). We report on our observed neurologic changes in addition to the cardiomyopathy. DESIGN/METHODS: case series, retrospective review, academic tertiary care hospitals. RESULTS: Six patients with the TTR 122 Ile gene mutation had amyloid staining on myocardial biopsies. All had symptoms of peripheral neuropathy. Causes of a peripheral neuropathy other than amyloid were excluded. All six patients had axonal dominant peripheral neuropathy, confirmed by NCV and EMG. One patient had a superimposed painful (narcotic requiring), lumbar radiculopathy, by EMG, without corresponding structural MRI abnormalities. One patient had multiple entrapment neuropathies (bilateral wrists and elbows), as well as, a prominent small fiber neuropathy documented by reduced intraepidermal nerve fiber density and autonomic nerve abnormalities with reduced sweat gland nerve fiber density. CONCLUSION: Val-122 Ile patients who are known to have amyloid cardiomyopathy may also have a peripheral neuropathy possibly due to amyloid deposition in the nerve. Clinical symptoms of radiculopathy confirmed by EMG may be explained by dural amyloid infiltration. Prospective studies of this phenotype are warranted to confirm these findings and to determine whether the peripheral neuropathy occurs earlier than the cardiomyopathy. Study Supported by: Not supported Disclosure: Dr. Khella has received personal compensation for activities with Pfizer Inc. as a member of a scientific advisory board. Dr. Drachman has nothing to disclose. Dr. Divito has nothing to disclose. Dr. Polydefkis has received personal compensation for activities with Johnson & Johnson as a consultant, and Biogen Idec as a scientific advisory board member. Dr. Brannagan has received personal compensation for activities with Grifols, Pfizer Inc., Biomarin Pharmaceutical, and Depomed, Inc. Dr. Judge has received personal compensation for activities with Pfizer Inc., Onyx Pharma, and Array Biopharma as a scientific advisor. Dr. Judge has received royalty payments from Genzyme Corp. Dr. Judge has received research support from Pfizer Inc. Dr. Maurer has received personal compensation for activities with Pfizer Inc. Dr. Maurer has received research support from Pfizer Inc.