GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case report.

Autor: Ho CC; Department of Clinical Pathology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Special Administrative Region, China., Tsung LL; Department of Paediatrics & Adolescent Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Special Administrative Region, China., Liu KT; Department of Paediatrics & Adolescent Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Special Administrative Region, China., Poon WT; Department of Clinical Pathology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Special Administrative Region, China. poonwt@ha.org.hk.
Jazyk: angličtina
Zdroj: BMC medical genetics [BMC Med Genet] 2018 Sep 12; Vol. 19 (1), pp. 162. Date of Electronic Publication: 2018 Sep 12.
DOI: 10.1186/s12881-018-0679-5
Abstrakt: Background: Mucolipidosis alpha/beta is an inborn error of metabolism characterized by deficiency of GlcNAc-1-phosphotransferase, in which essential alpha/beta subunits are encoded by the GNPTAB gene. The autosomal recessive condition is due to disruptions of hydrolase mannose 6-phosphate marker generation, defective lysosomal targeting and subsequent intracellular accumulation of non-degraded material. Clinical severity depends on residual GlcNAc-1-phosphotransferase activity, which distinguishes between the milder type III disease and the severe, neonatal onset type II disease.
Case Presentation: We report the clinical, biochemical and genetic diagnosis of mucolipidosis III alpha/beta in a two-year-old Chinese boy who initially presented with poor weight gain, microcephaly and increased tone. He was confirmed to harbor the common splice site mutation c.2715 + 1G > A and the nonsense variant c.2404C > T (p.Q802*). Clinically, the patient had multiple phenotypic features typical of mucopolysaccharidosis including joint contractures, coarse facial features, kypho-lordosis, pectus carinatum and umbilical hernia. However, the relatively mild developmental delay compared to severe type I and type II mucopolysaccharidosis and the absence of macrocephaly raised the possibility of the less commonly diagnosed mucolipidosis alpha/beta. Critical roles of lysosomal enzyme activity assay, which showed elevated α-iduronidase, iduronate sulfatase, galactose-6-sulphate sulphatase, arylsulfatase B and α-hexosaminidase activities; and genetic study, which confirmed the parental origin of both mutations, were highlighted.
Conclusions: The recently reported nonsense variant c.2404C > T in the GNPTAB gene is further recognized and this contributes to the genotype-phenotype spectrum of mucolipidosis alpha/beta.
Databáze: MEDLINE
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