THE GENOTYPE AND PHENOTYPE STUDIES OF 40 CHINESE PATIENTS WITH X-ALD

Objectives: to studies the genotype and phenotype of 40 Chinese patients with X-ALD.

Methods: Clinical features of 40 Chinese patients with X-ALD were studies and mutation spectrums were investigated by polymerase chain reaction (PCR) and sequencing.

Results: Among these patients, four were siblings from two kindreds, the others were unrelated. There were 31 cases with childhood cerebral, 8 cases with adolescent cerebral and 1 case with adrenomyeloneuropathy. Visual impairment, which presented in 12 cases (30%), is the most common initial symptom. Nine (69%) of 13 cases who had plasma hydrocortisone and ACTH test showed adrenal insufficiency. During the follow-up period, 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, their disease courses 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. Two patients with long disease course had a missence mutation c.1559 T>A and a nonsense mutation c.1785 G>A respectively. The siblings with similar manifestations were observed in two families, whose mutations were c.887 A>G and c.1028 G>T.

Conclusion: The phenotypes, disease severity and rate of neurodegeneration can't be predicted by the nature of mutations.