Abstract Details

Title Familial Amyloid Polyneuropathy: Impact of Biopsies and Mutations on Diagnostic Considerations

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 12-033

Objective To characterize the symptoms, signs and skin biopsy neuropathological findings in a cohort of individuals with TTR Mutations.

Background Familial amyloid polyneuropathy is due to one of many mutations in the transthyretin(TTR) gene, resulting in a progressive fatal disease with sensory, motor and autonomic involvement.

Design/Methods Individuals with a variety of TTR mutations underwent detailed neurological examinations including the Neuropathy Impairment Score in the Lower Limb(NIS-LL), the Utah Early Neuropathy Score(UENS), Coutinho staging, autonomic testing, symptom scores (using the EuroQol, Brief Pain Symptom Inventory, and the orthostatic hypotension Questionnaire). All subjects had 3mm punch skin biopsies at the distal leg and distal thigh with analysis of amyloid burden by Congo Red, and neuropathy severity by staining with protein gene product 9.5.

Results A total of 88 subjects participated with the following TTR mutations: 43- Val30Met, 30- Ser50Arg, 6- Gly47Ala, 5- Ser52Pro, 2- F64L, 1- I73V and 1 with Y136H. Coutinho staging included 47 stage 0, 32 stage 1, 8 stage 2 and 1 stage 3. The diagnostic sensitivity for amyloid detection from a single skin biopsy was 72%, the diagnostic yield increased to 89% with 2 biopsies. Biopsies were positive for amyloid in 78% of individuals with no clinical evidence of neuropathy (NIS-LL scores of 0) and 94% for individuals with any evidence of neuropathy. Amyloid burden was inversely correlated with nerve density at the distal leg (R=0.59,P<0.01) and distal thigh(R=-0.53,P<0.01), and correlated with the NIS-LL (R=0.48,P<0.05), and UENS (R=0.49,P<0.05).

Conclusions Skin biopsy is a sensitive and specific pathological marker for tissue diagnosis of familial amyloid polyneuropathy across multiple mutations, even in individuals with no clinical evidence of disease. Amyloid burden correlates with neuropathy severity, both pathologically and by examination criteria; skin biopsies may prove informative for studies that seek to alter the natural history of the disease.

Authors/Disclosures
Christopher H. Gibbons, MD, FAAN (Beth Israel Deaconess Medical Center) PRESENTER	Dr. Gibbons has received personal compensation for serving as an employee of CND Life Sciences. Dr. Gibbons has or had stock in CND Life Sciences.Dr. Gibbons has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
Fabio Adrian Barroso, MD	Fabio Adrian Barroso, MD has nothing to disclose.
Marta Campagnolo	No disclosure on file
Sharika Rajan, MD (NIH)	Dr. Rajan has nothing to disclose.
Roy L. Freeman, MD (Beth Israel Deaconess Hosp)	Dr. Freeman has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Cutaneous Diagnostic Life Sciences. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vertex. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Theravance. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Inhibikase. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Freeman has received research support from NIH. The institution of Dr. Freeman has received research support from Theravance. The institution of Dr. Freeman has received research support from Biohaven. The institution of Dr. Freeman has received research support from Lundbeck. Dr. Freeman has received research support from Regeneron.

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