AB067. X-linked adrenoleukodystrophy: Phenotype and genotype in Vietnamese patients
Newborn Screening, Inborn Errors of Metabolism

AB067. X-linked adrenoleukodystrophy: Phenotype and genotype in Vietnamese patients

Khanh Ngoc Nguyen1, Ha Thu Nguyen1, Ngoc Thi Bich Can1, Thao Phuong Bui1, Shimozawa Nobuyuki2, Huynh Anh Vu3, Mai Thi Thanh Do1, Dung Chi Vu1

1Department of Endocrinology, Metabolism, Genetics, Vietnam National Children’s Hospital, Hanoi, Vietnam;2Division of Genomics Research, Life Science Research Center, Department of Pediatrics, Gifu University, Gifu, Japan;3Center for Molecular Biomedicine, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam

Background: X-linked adrenoleukodystrophy (X-ALD) is caused by a defect in the gene ABCD1, which maps to Xq28 and codes for a peroxisomal membrane protein that is a member of the ATP-binding cassette transporter superfamily. This disease characterized by progressive neurologic dysfunction, occasionally associated with adrenal insufficiency. Objective is to identify phenotype and genotype in Vietnamese patients with X-ALD.

Methods: Genomic DNA from 20 Vietnamese patients from 18 unrelated families was extracted using standard procedures from the peripheral blood leukocytes. Mutation analysis of ABCD1 was performed using polymerase chain reaction (PCR) and DNA direct sequencing.

Results: We identified 17 different mutations of ABCD1 in 20 patients including missense mutations (2/17), deletion (4/17), frameshift mutation (1/17) and splice site mutation (1/17). Of which, six novel mutations including c.1202G>T (p.Arg401Trp); c.1208T>A (p.Met403Lys); IVS8+28-551bp del; c.1668G>C (p.Q556H); c.292_296delTCGGC (p.S98RfsX95); and 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 in six unrelated patients. Eleven reported mutations including c.796G>A (p.Gly266Arg); c.1628C>T (p.Pro543Leu); c.1553G>A (p.Arg518Gln); c.1552 C>T (p.Arg518Trp); c.854G>C (p.R285P); c.1825G>A (p.E609K); c.1415_1416delAG (p.Q472RfsX83) and c.46-53del insG, c.1553G>A (p.Arg518Gln), c.1946-1947insA (p.Asp649fsX733), c.1978C>T (p.Arg660Trp) were identified in 14 patients from 12 families. Most of patients (17/20) presented cerebral ALD type with/without adrenal insufficiency and only 3 patients presented Addison type.

Conclusions: Mutation analysis of ABCD1 gene helped confirmation of diagnosis of X-ALD, genetic counselling and prenatal diagnosis but could not be used to predict the specific phenotype of X-ALD.

Keywords: X-linked adrenoleukodystrophy (X-ALD); ABCD1 mutations

doi: 10.21037/atm.2017.s067

Cite this article as: Nguyen KN, Nguyen HT, Can NT, Bui TP, Nobuyuki S, Vu HA, Do MT, Vu DC. X-linked adrenoleukodystrophy: Phenotype and genotype in Vietnamese patients. Ann Transl Med 2017;5(Suppl 2):AB067. doi: 10.21037/atm.2017.s067

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