Background: The X linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease caused by defects of the ABCD1 gene on chromosome Xq28. This disease is characterized by progressive neurologic dysfunction, and occasionally associated with adrenal insufficiency. The estimated frequency is about 1:42000 in male, whereas the estimated frequency for heterozygous women is 1:14000. There was no correlation between genotype and phenotype of X-ALD patients.
Objective: To describe phenotype and genotype in affected male patients in Vietnamese patients with X-ALD.
Method: This is case series study. Clinical features, biochemical finding, cerebral MRI lesions and genetic testing of 23 cases from 20 unrelated families were studied.
Results: Age of onset was between 1.5 and 14 years. Most of patients had symptoms including cognitive impairment, extrapyramidal signs and/or hyperpigmentation, adrenal crisis,low serum cortisol levels, and increased plasma ACTH levels. Neuroimaging studies (cerebral MRI) showed classical patterns in all patients with neurological symptoms. Cerebral ALD (has worse prognosis, high mortality rates.We identified 19 different causative mutations of ABCD1 in 23 patients including missense mutations (13/19), deletion (4/19), nonsense mutation (1/19) and splice site mutation (1/19). Of which, eight novel mutations in six unrelated patients including c.1202G>T (p.Arg401Trp); c.1208T>A (p.Met403Lys); IVS8+28-551bp del; c.1668G>C (p.Gln556His);c.292_296delTCGGC (p.S98RfsX95); c.1946_1947insA (p.Asp649fsX733), c.46-53del insGand the extent of deletion included between IVS1+505 and IVS2+1501, containing whole the exon 2 (4243bp), plus insertion of 79bp from BAP31 and 8bp from unknown origin in this deleted region were identified.But we did not clarify the genotype phenotype correlations.
Conclusion: Children with X-Linked Adrenoleukodystrophyshould be performed mutation analysis which helps in making diagnosis and treatment decision. We should do genetic testing for patient's family member, especially female to diagnosis female affected. Families of children with X-ALD should be given genetic counseling.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology