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. 2015 Apr;51(4):489-95.
doi: 10.1002/mus.24336. Epub 2015 Feb 11.

Natural history and biomarkers in hereditary sensory neuropathy type 1

Vera Fridman  1 , Anne Louise Oaklander, William S David, Elise A Johnson, Jessica Pan, Peter Novak, Robert H Brown Jr, Florian S Eichler
Affiliations

Natural history and biomarkers in hereditary sensory neuropathy type 1

Vera Fridman et al. Muscle Nerve. 2015 Apr.

Abstract

Introduction: Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is most commonly caused by missense mutations in SPTLC1. In this study we mapped symptom progression and compared the utility of outcomes.

Methods: We administered retrospective surveys of symptoms and analyzed results of nerve conduction, autonomic function testing (AFT), and PGP9.5-immunolabeled skin biopsies.

Results: The first symptoms were universally sensory and occurred at a median age of 20 years (range 14-54 years). The onset of weakness, ulcers, pain, and balance problems followed sequentially. Skin biopsies revealed universally absent epidermal innervation at the distal leg with relative preservation in the thigh. Neurite density was highly correlated with total Charcot-Marie-Tooth Examination Score (CMTES; r2 = -0.8) and median motor amplitude (r2 = -0.75).

Conclusions: These results confirm sensory loss as the initial symptom of HSAN1 and suggest that skin biopsy may be the most promising biomarker for future clinical trials.

Keywords: hereditary neuropathy; neurogenetics; peripheral neuropathy; skin biopsy; small fiber neuropathy.

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Figures

Figure 1
Figure 1
Cumulative incidence of symptoms in HSAN1 (n = 23).
Figure 2
Figure 2
Skin biopsy section from the thigh showing loss of intraepidermal nerve fibers (black arrows) in a representative HSAN1 patient (A) as compared with an age-matched control (B) with normal distribution of dermal and intraepidermal nerve fibers.
See this image and copyright information in PMC

References

    1. Auer-Grumbach M, de Jonghe P, Verhoeven K, Timmerman V, Wagner K, Hartung HP, et al. Autosomal dominant inherited neuropathies with prominent sensory loss and mutilations. Arch Neurol. 2003;60:329–334. - PubMed
    1. Houlden H, King R, Blake J, Groves M, Love S, Woodward C, et al. Clinical, pathological and genetic characterization of hereditary sensory and autonomic neuropathy type I (HSAN I) Brain. 2006;129:411–425. - PubMed
    1. Denny-Brown D. Hereditary sensory radicular neuropathy. J Neurol Neurosurg Psychiatry. 1951;14:237–252. - PMC - PubMed
    1. Lindahl AJ, Lhatoo SD, Campbell MJ, Nicholson G, Love S. Late-onset hereditary sensory neuropathy type I due to SPTLC1 mutation: autopsy findings. Clin Neurol Neurosurg. 2006;108:780–783. - PubMed
    1. Reimann HA, McKechnie WG, Stanisavljevic S. Hereditary sensory radicular neuropathy and other defects in a large family: reinvestigation after twenty years and report of a necropsy. Am J Med. 1958;25:573–579. - PubMed

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