Neurophysiology and Intraepidermal Nerve Fiber Density in Hereditary Sensory and Autonomic Neuropathy Type 1 (HSAN1) (P03.202)

Abstract

Objective: To quantify the impact of the SPTLC1 mutation upon neurological outcome measures in HSAN1 patients. Background Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is the most common inherited neuropathy to predominantly affect sensory neurons. The disorder is caused by mutations in SPTCL1, which encodes the enzyme serine palmitoyltransferase. Design/Methods: We studied two HSAN1 families with different mutations (n = 8). Five patients carried the C133Y mutation, three the C133W mutation. The median age was 34 years (range 26-59); the median age of onset was 19 (range 15-54). All eight patients underwent neurological examination and were scored using the CMT symptom score (CMTSS). Nerve conduction studies (NCS) of the upper and lower extremities were conducted in all (including 3 motor NCS and 4 sensory NCS). Six patients had skin biopsies at the distal leg and proximal thigh to assess the intraepidermal nerve fiber density (IENFD). Results: The average CMTSS was 12.38 (SD +/-6.74). All patients complained of neuropathic pain apart from two patients who had the highest CMTSS. Sensory symptoms (average score 2.9) were prominent but motor symptoms (average score 1.2) were present as well. No sensory responses were obtainable in 5/8; lower extremity motor responses were absent in 6/8 patients. None of these 6 patients had epidermal nerve fibers detected at the distal leg, while they were present in the thigh in all patients. The correlation coefficient between CMTSS and IENFD was -0.8 and between CMTSS and median motor amplitudes was -0.75. Conclusions: Beyond sensory there is also motor impairment present in HSAN1 patients. In our limited sample size we found an inverse correlation between both CMTSS and IENFD and CMTSS and nerve conduction studies. This study provides important clinical characterization of both neurophysiology and the IENFD in HSAN1. Disclosure: Dr. David has nothing to disclose. Dr. Oaklander has nothing to disclose. Dr. Pan has nothing to disclose. Dr. Novak has nothing to disclose. Dr. Brown has received personal compensation for activities as an advisory board member. Dr. Eichler has nothing to disclose.