GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case report
Abstract 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 ma...
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| Language: | English |
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BMC
2018-09-01
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| Series: | BMC Medical Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12881-018-0679-5 |
| _version_ | 1818613795394682880 |
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| author | Chi-Chun Ho Lilian Li-Yan Tsung Kam-Tim Liu Wing-Tat Poon |
| author_facet | Chi-Chun Ho Lilian Li-Yan Tsung Kam-Tim Liu Wing-Tat Poon |
| author_sort | Chi-Chun Ho |
| collection | DOAJ |
| description | Abstract 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. |
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| language | English |
| last_indexed | 2024-12-16T16:07:48Z |
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| series | BMC Medical Genetics |
| spelling | doaj.art-a4b7291b8f9a449080e9a4df6c16efc92022-12-21T22:25:18ZengBMCBMC Medical Genetics1471-23502018-09-011911710.1186/s12881-018-0679-5GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case reportChi-Chun Ho0Lilian Li-Yan Tsung1Kam-Tim Liu2Wing-Tat Poon3Department of Clinical Pathology, Pamela Youde Nethersole Eastern HospitalDepartment of Paediatrics & Adolescent Medicine, Pamela Youde Nethersole Eastern HospitalDepartment of Paediatrics & Adolescent Medicine, Pamela Youde Nethersole Eastern HospitalDepartment of Clinical Pathology, Pamela Youde Nethersole Eastern HospitalAbstract 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.http://link.springer.com/article/10.1186/s12881-018-0679-5Mucolipidosis III alpha/betaPseudo-hurler polydystrophyGlcNAc-1-phosphotransferaseGNPTABNonsense variantP.Q802* |
| spellingShingle | Chi-Chun Ho Lilian Li-Yan Tsung Kam-Tim Liu Wing-Tat Poon GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case report BMC Medical Genetics Mucolipidosis III alpha/beta Pseudo-hurler polydystrophy GlcNAc-1-phosphotransferase GNPTAB Nonsense variant P.Q802* |
| title | GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case report |
| title_full | GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case report |
| title_fullStr | GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case report |
| title_full_unstemmed | GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case report |
| title_short | GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case report |
| title_sort | gnptab c 2404c t nonsense mutation in a patient with mucolipidosis iii alpha beta a case report |
| topic | Mucolipidosis III alpha/beta Pseudo-hurler polydystrophy GlcNAc-1-phosphotransferase GNPTAB Nonsense variant P.Q802* |
| url | http://link.springer.com/article/10.1186/s12881-018-0679-5 |
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