title: Phenotypic characteristics of early Wolfram syndrome.
abstract: BACKGROUND
  Wolfram Syndrome (WFS:OMIM 222300) is an autosomal recessive, progressive, neurologic and endocrinologic degenerative disorder caused by mutations in the WFS1 gene, encoding the endoplasmic reticulum (ER) protein wolframin, thought to be involved in the regulation of ER stress. This paper reports a cross section of data from the Washington University WFS Research Clinic, a longitudinal study to collect detailed phenotypic data on a group of young subjects in preparation for studies of therapeutic interventions.
  
  
  METHODS
  Eighteen subjects (ages 5.9-25.8, mean 14.2 years) with genetically confirmed WFS were identified through the Washington University International Wolfram Registry. Examinations included: general medical, neurologic, ophthalmologic, audiologic, vestibular, and urologic exams, cognitive testing and neuroimaging.
  
  
  RESULTS
  Seventeen (94%) had diabetes mellitus with the average age of diabetes onset of 6.3 ± 3.5 years. Diabetes insipidus was diagnosed in 13 (72%) at an average age of 10.6 ± 3.3 years. Seventeen (94%) had optic disc pallor and defects in color vision, 14 (78%) had hearing loss and 13 (72%) had olfactory defects, eight (44%) had impaired vibration sensation. Enuresis was reported by four (22%) and nocturia by three (17%). Of the 11 tested for bladder emptying, five (45%) had elevated post-void residual bladder volume.
  
  
  CONCLUSIONS
  WFS causes multiple endocrine and neurologic deficits detectable on exam, even early in the course of the disease. Defects in olfaction have been underappreciated. The proposed mechanism of these deficits in WFS is ER stress-induced damage to neuronal and hormone-producing cells. This group of subjects with detailed clinical phenotyping provides a pool for testing proposed treatments for ER stress. Longitudinal follow-up is necessary for establishing the natural history and identifying potential biomarkers of progression.
authors: Bess A
authors: BA
authors: Marshall
authors: M Alan
authors: MA
authors: Permutt
authors: Alexander R
authors: AR
authors: Paciorkowski
authors: James
authors: J
authors: Hoekel
authors: Roanne
authors: R
authors: Karzon
authors: Jon
authors: J
authors: Wasson
authors: Amy
authors: A
authors: Viehover
authors: Neil H
authors: NH
authors: White
authors: Joshua S
authors: JS
authors: Shimony
authors: Linda
authors: L
authors: Manwaring
authors: Paul
authors: P
authors: Austin
authors: Timothy E
authors: TE
authors: Hullar
authors: Tamara
authors: T
authors: Hershey
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003117:Color Vision Defects / Q000503:physiopathology; D004721:Endoplasmic Reticulum / Q000473:pathology; D005260:Female; D034381:Hearing Loss / Q000503:physiopathology; D006801:Humans; D008297:Male; D014929:Wolfram Syndrome / Q000503:physiopathology*; D055815:Young Adult
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