A novel frameshift mutation of HEXA gene in the first family with classical infantile Tay-Sachs disease in Thailand

摘要

Tay-Sachs disease (TSD) is an autosomal recessive neurodegenerative disorder caused by mutations in the HEXA gene resulting in a deficiency of beta-hexosaminidase A (HEX A) enzyme. To our knowledge, TSD has never been reported in Thai population. We describe the first case of classic infantile TSD in a 2-year-old Thai boy who presented with first episode of seizure and neuroregression since 9 months of age. Hyperacusis, progressive macrocephaly and macular cherry red spots were also detected during examination. Brain MRI revealed hyperintensity in the basal ganglion on T1-weighted and partial corpus callosum agenesis. Measurement of beta-hexosaminidase activity in the patient leukocytes showed low total beta-hexosaminidase (62.6 normal 801+/-190 nmol/mg protein/hr) and low % HEX A (7.57 normal 55-72% HEX A) activity compatible with TSD. Mutation analysis of the HEXA gene revealed compound heterozygous of a novel frameshift mutation (c.1207delG or p.E403SfsX20) in exon 11 which was inherited from the mother and a previously described missense mutation (c.1510C>T or p.R504C) in exon 13 which was inherited from the father, respectively. Conclusion. We report a clinical, biochemical and molecular analysis in the first case of genetically confirmed classic infantile TSD in Thailand.