title: Sjögren-Larsson syndrome: clinical and MRI/MRS findings in FALDH-deficient patients.
abstract: OBJECTIVE
  To determine the spectrum of clinical and MRI/1H MRS features of patients with fatty aldehyde dehydrogenase (FALDH) deficiency.
  
  
  BACKGROUND
  The Sjogren-Larsson syndrome (SLS) was originally defined as a clinical triad consisting of ichthyosis, spastic di- or tetralegia, and mental retardation, with autosomal recessive inheritance. By now, both the deficiency of the enzyme FALDH, and the genetic mutations on chromosome 17 responsible for this deficiency, have been identified. SLS, defined by fibroblast FALDH deficiency, seems to be a much broader syndrome.
  
  
  METHODS
  The clinical findings of 11 FALDH-deficient patients of different ages and one patient with the characteristic SLS-like ichthyosis, but without FALDH deficiency, were evaluated in relation to their cerebral MRI, and to 1H MRS in six patients.
  
  
  RESULTS
  The severity of neurologic symptoms showed considerable variation. Fundoscopic perifoveal glistening dots and the characteristic SLS-like ichthyosis were present in all patients. Serial MRI findings showed evidence of retarded myelination and a variable degree of dysmyelination. 1H MRS showed an accumulation of free lipids in the periventricular white matter, even before the stage of visible dysmyelination.
  
  
  CONCLUSIONS
  The neurologic consequences of FALDH deficiency show considerable variation. The characteristic pattern of ichthyosis and retinal degeneration are seen consistently, yet they are not pathognomonic. MRI and 1H MRS findings suggest an accumulation of long-chain fatty alcohol intermediates, resulting in retarded myelination and dysmyelination.
authors.affiliation: Department of Neurology, Laurentius Hospital, Roermond, The Netherlands.
authors.forename: P H
authors.initials: PH
authors.lastname: van Domburg
authors.forename: M A
authors.initials: MA
authors.lastname: Willemsen
authors.forename: J J
authors.initials: JJ
authors.lastname: Rotteveel
authors.forename: J G
authors.initials: JG
authors.lastname: de Jong
authors.forename: H O
authors.initials: HO
authors.lastname: Thijssen
authors.forename: A
authors.initials: A
authors.lastname: Heerschap
authors.forename: J R
authors.initials: JR
authors.lastname: Cruysberg
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
authors.forename: F J
authors.initials: FJ
authors.lastname: Gabreëls
authors.forename: P M
authors.initials: PM
authors.lastname: Steijlen
mesh_terms: D000293:Adolescent; D000328:Adult; D000445:Aldehyde Oxidoreductases / Q000172:deficiency*; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011859:Radiography; D012160:Retina / Q000000981:diagnostic imaging; D016111:Sjogren-Larsson Syndrome / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology
chemical_list: D000445:Aldehyde Oxidoreductases; C038828:long-chain-aldehyde dehydrogenase