title: The genotype and phenotype studies of 40 Chinese patients with X-linked adrenoleukodystrophy (X-ALD).
abstract: OBJECTIVE
  To elucidate the phenotype and the genotype-phenotype correlations in Chinese patients with X-linked adrenoleukodystrophy (X-ALD).
  
  
  METHODS
  Clinical features of 40 Chinese patients with X-ALD were studied and mutation spectrums were investigated by polymerase chain reaction (PCR) and sequencing.
  
  
  RESULTS
  Among these patients, four were siblings from two unrelated families, the others were unrelated. There were 31 cases with childhood cerebral (CCALD), 8 cases with adolescent cerebral (ACALD) and 1 case with adrenomyeloneuropathy (AMN). Visual impairment, which presented in 12 cases (30%), was the most common initial symptom. Nine (69%) of 13 cases who had hydrocortisone and ACTH measured showed adrenal insufficiency. By follow-up date, 19 cases (47.5%) were dead. The interval from onset to death varied from 1 to 6 years and the average were 3.3 years. The mean age at death was 10.5 years. Eleven cases (27.5%) were in vegetable state. The mean interval from onset to apparently vegetable state was 2.8 years (range from 1 to 6 years). Four cases had progressive neurological disability. Four cases were lost follow-up. One case with CCALD and one case with ACALD progressed slowly. The courses of the disease of these two patients were 5 years and 15 years respectively. Thirty five mutations were identified in 40 cases. Most were located within exon 1-3 (40%, 16/40) and exon 6-8 (42%, 17/40). There is a distinct clustering of missense mutations in exon 6 (17%, 7/40). Five types of mutations were associated with CCALD, three with ACALD and a missense mutation was identified in the patients with AMN. The two patients with long disease courses had a missense mutation c.1559 T>A and a nonsense mutation c.1785 G>A respectively. The siblings with similar manifestations and onset age were observed in two families, whose mutations were c.887 A>G and c.1028 G>T.
  
  
  CONCLUSIONS
  The phenotypes, disease severity and rate of neurodegeneration could not be predicted by the nature of mutations.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Li-li
authors.initials: LL
authors.lastname: Ping
authors.forename: Xin-hua
authors.initials: XH
authors.lastname: Bao
authors.forename: Ai-hua
authors.initials: AH
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
authors.forename: Yue-hua
authors.initials: YH
authors.lastname: Zhang
authors.forename: Yu-wu
authors.initials: YW
authors.lastname: Jiang
authors.forename: Jiong
authors.initials: J
authors.lastname: Qin
authors.forename: Xi-ru
authors.initials: XR
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000235:genetics*; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D055815:Young Adult