title: Natural history and biomarkers in hereditary sensory neuropathy type 1.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts, 02114, USA.
authors.forename: Vera
authors.initials: V
authors.lastname: Fridman
authors.forename: Anne Louise
authors.initials: AL
authors.lastname: Oaklander
authors.forename: William S
authors.initials: WS
authors.lastname: David
authors.forename: Elise A
authors.initials: EA
authors.lastname: Johnson
authors.forename: Jessica
authors.initials: J
authors.lastname: Pan
authors.forename: Peter
authors.initials: P
authors.lastname: Novak
authors.forename: Robert H
authors.initials: RH
authors.lastname: Brown
authors.forename: Florian S
authors.initials: FS
authors.lastname: Eichler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002607:Charcot-Marie-Tooth Disease / Q000503:physiopathology; D003625:Data Collection; D005260:Female; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000502:physiology*; D012189:Retrospective Studies; D012867:Skin / Q000294:innervation* / Q000473:pathology*; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: hereditary neuropathy; neurogenetics; peripheral neuropathy; skin biopsy; small fiber neuropathy