Novel HEXA variants in Korean children with Tay-Sachs disease with regression of neurodevelopment from infancy.

Autor: Park JH; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea., Ko JM; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea.; Rare Disease Center, Seoul National University Hospital, Seoul, Korea., Kim MS; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea., Kim MJ; Rare Disease Center, Seoul National University Hospital, Seoul, Korea.; Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea., Seong MW; Rare Disease Center, Seoul National University Hospital, Seoul, Korea.; Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea., Yoo T; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea., Lim BC; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea.; Rare Disease Center, Seoul National University Hospital, Seoul, Korea., Chae JH; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea.; Rare Disease Center, Seoul National University Hospital, Seoul, Korea.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2021 Jun; Vol. 9 (6), pp. e1677. Date of Electronic Publication: 2021 Apr 03.
DOI: 10.1002/mgg3.1677
Abstrakt: Background: Tay-Sachs disease (TSD) is a lysosomal storage disease caused by mutations in the HEXA gene that encodes the HexosaminidaseA (HEXA) enzyme. As HEXA normally functions to degrade the protein GM2-ganglioside in lysosomes, decreased levels of HEXAcauses an accumulation of the protein and leads to neurological toxicity. Typical clinical manifestations of TSD include neurodevelopmental regression, muscle weakness, hypotonia, hyperreflexia, ataxia, seizures, and other neurological symptoms. It is quite rare in Asian populations, wherein only two cases have been reported in Korea to date.
Methods: Clinical records, radiological assessments, and laboratory findings, such as plasma hexosaminidase assay and HEXA analysis, were extracted from the medical records of three (1 male and 2 female) independent Korean children with infantile form of Tay-Sachs disease.
Results: All three children presented with neurodevelopmental regression and strabismus at around 8 months of age. Presence of cherry-red spots in the macula led to conduction of biochemical and genetic studies for TSD confirmation. The plasma hexosaminidase assay revealed decreased HEXA activity and low to normal total hexosaminidase activity. Similarly, genetic analysis revealed 4 variants from 6 alleles, including 2 previously reported and 2 novel variants, in the HEXA gene.
Conclusion: We presented three Korean children, who were recently diagnosed with infantile-type TSDvia enzyme assay and genetic analysis. Furthermore, results showed that fundus examination can be helpful for early diagnosis of children with neurodevelopmental regression.
(© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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