title: Neurological impairment among heterozygote women for X-linked Adrenoleukodystrophy: a case control study on a clinical, neurophysiological and biochemical characteristics.
abstract: BACKGROUND
  Neurologic impairments in female heterozygotes for X-linked Adrenoleukodystrophy (X-ALD) are poorly understood. Our aims were to describe the neurological and neurophysiological manifestations of a cohort of X-ALD heterozygotes, and to correlate them with age, disease duration, mutations, X-inactivation and serum concentrations of a marker of neuronal damage, neuron-specific enolase (NSE).
  
  
  METHODS
  All 45 heterozygotes identified in our region, with previous VLCFA and molecular diagnosis, were invited to be evaluated through myelopathy scales JOA and SSPROM, nerve conduction studies and somatosensory evoked responses. X inactivation pattern was tested by HUMARA methylation assay. Serum NSE was measured by eletrochemiluminescense.
  
  
  RESULTS
  Thirty three heterozygote women were recruited: 29 (87%) were symptomatic. Symptomatic and asymptomatic women presented different m ± sd ages (43.9 ± 10.2 versus 24.3 ± 4.6), JOA (14.5 ± 1.7 versus 16.6 ± 0.2) and SSPROM (86.6 ± 7.9 versus 98.4 ± 1.1) scores (p<0.05). Both JOA (r=-0.68) and SSPROM (r=-0.65) correlated with age, irrespectively of the disease status (p=0.0001, Spearman). Delayed latencies in the central ascending conduction studies on the lower limbs were present in 72% of all heterozygotes, and correlated with SSPROM (r=-0.47, p=0.018, Spearman). NSE values were higher in heterozygote than in control women (12.9 ± 7 and 7.2 ± 7 ng/ml, p=0.012, Mann-Whitney U). Mutation severity and inactivation patterns were not associated with neurologic status.
  
  
  CONCLUSIONS
  Neurologic manifestations, clearly related to age, were quite common in the present cohort. JOA and SSPROM scales were able to discriminate the asymptomatic from the symptomatic heterozygotes. Both scales might be useful tools to follow disease progression, in future studies.
authors.forename: Clarissa Troller
authors.initials: CT
authors.lastname: Habekost
authors.forename: Pedro
authors.initials: P
authors.lastname: Schestatsky
authors.forename: Vitor Felix
authors.initials: VF
authors.lastname: Torres
authors.forename: Daniella Moura
authors.initials: DM
authors.lastname: de Coelho
authors.forename: Carmen Regla
authors.initials: CR
authors.lastname: Vargas
authors.forename: Vitor
authors.initials: V
authors.lastname: Torrez
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Oses
authors.forename: Luis Valmor
authors.initials: LV
authors.lastname: Portela
authors.forename: Fernanda dos Santos
authors.initials: Fdos S
authors.lastname: Pereira
authors.forename: Ursula
authors.initials: U
authors.lastname: Matte
authors.affiliation: Post-Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. ljardim@hcpa.ufrgs.br.
authors.forename: Laura Bannach
authors.initials: LB
authors.lastname: Jardim
mesh_terms: D000326:Adrenoleukodystrophy / Q000473:pathology* / Q000503:physiopathology*; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009422:Nervous System Diseases / Q000175:diagnosis* / Q000209:etiology