Abstract Details

Title Hereditary Sensory Autonomic Neuropathy Type-1C (HSAN1c) by a Novel Mutation of Asn177Asp in SPTELCS2 Gene

Topic Neuromuscular and Clinical Neurophysiology (EMG)

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

Poster/Presentation
Number 12-035

Objective To characterize a family with HSAN1c associated with a missense mutation of Asn177Asp.

Background Patients with hereditary sensory autonomic neuropathies 1c (HSAN1c) typically experience sensory loss, distal limb weakness and variable autonomic dysfunction. Through studies in several large families, a few heterozygous missense mutations in the SPTLC2 gene on chromosome 14q24 have been identified to cause HSAN1c. These mutations result in impaired serine palmitoyltransferase (SPT), which catalyzes the first step in sphingolipid biosynthesis, leading to accumulation of neurotoxic 1-deoxysphinganine that can be reversed by diet modification. In this study, we describe a family with a novel missense mutation in SPTLC2.

Design/Methods Three affected members were evaluated by neurological examination, nerve conduction study (NCS), and genetic testing. One non-affected family member also underwent genetic testing.

Results All three affected men (ages 26, 32, and 35) had normal development and excelled in athletics up to high school. They became symptomatic around early 20s when they reported tripping, weak ankles, fatigue and muscle atrophy in distal legs. They experienced minimal numbness in feet and distal legs. None reported significant autonomic symptoms. CMT Neuropathy Scores for measuring disabilities were 17, 24, and 25, respectively. Additionally their mother, two aunts, and a cousin are symptomatic but have not been evaluated by us. NCS in the three affected members showed sensorimotor polyneuropathy with intermediately slowed conduction velocities. Genetic testing revealed that the three brothers shared the Asn177Asp mutation in SPTLC2, which was not found in their asymptomatic aunt.

Conclusions Asn177Asp mutation in SPTLC2 has not been reported in patients with HSAN1c. The phenotype in this family reveals several unique features. Symptoms are predominantly of motor deficits, but no or minimal sensory or autonomic complaints. In addition, conduction velocities are in the intermediate range similar to the pattern seen in patients with CMTX1.

Authors/Disclosures
Taylor R. Anderson, MD (Trinity Health Muskegon) PRESENTER	Dr. Anderson has nothing to disclose.
	No disclosure on file
Jun Li, MD, PhD, FAAN (Harris Methodist Hospital)	The institution of Dr. Li has received personal compensation in the range of $500-$4,999 for serving as a Consultant for FDA. The institution of Dr. Li has received research support from NIH. Dr. Li has a non-compensated relationship as a Associate Editor of ACTN journal with ANA that is relevant to AAN interests or activities.

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