Tay-Sachs disease (TSD) is an autosomal recessive neurodegenerative disorder caused by mutations in the HEXA gene resulting in a deficiency of β-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 β-hexosaminidase activity in the patient leukocytes showed low total β-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.
Tay-Sachs Disease

A boy, aged 5 years, attended the hospital due to progressive psychomotor regression for 2.5 years. Motor function regression was the main manifestation in the early stage, and brain MRI and whole-exome sequencing (WES) of the family showed no abnormalities. After the age of 4 years and 9 months, the boy developed cognitive function regression, and brain MRI showed cerebellar atrophy. The reanalysis of WES results revealed a compound heterozygous mutation, [NM_000520, c.784C>T(p.His262Tyr]), c.1412C>T(p.Pro471Leu)], in the HEXA gene. The enzyme activity detection showed a significant reduction in the level of β-hexosaminidase encoded by this gene. The boy was diagnosed with juvenile Tay-Sachs disease (TSD). TSD has strong clinical heterogeneity, and cerebellar atrophy may be an important clue for the diagnosis of juvenile TSD. The reanalysis of genetic data when appropriate based on disease evolution may improve the positive rate of WES.
Atrophy ; Humans ; Magnetic Resonance Imaging ; Male ; Mutation ; Tay-Sachs Disease/genetics*

Tay-Sachs Disease (TSD), the most common form of GM(2) gangliosidosis, is an autosomal recessive inborn lysosomal glycosphingolipid storage disease which is resulted from the mutations that affect the alpha-subunit locus on chromosome 15 and cause a severe deficiency of hexosaminidase A. It is characterized by normal motor development in the first few months of life, followed by progressive weakness and loss of motor skills beginning around 6 months of life. Neurodegeneration is relentless and manifested as relentless motor and mental deterioration, beginning with motor incoordination, mental obtundation leading to muscular flaccidity, blindness, and increasing dementia, with death occurring by the age of 4 or 5 years. We report a successful anesthetic management in a patient with Tay-Sachs Diseases for tracheostomy and feeding gastrostomy.
Ataxia ; Blindness ; Chromosomes, Human, Pair 15 ; Dementia ; Gangliosidoses ; Gastrostomy ; Hexosaminidase A ; Hexosaminidases ; Humans ; Motor Skills ; Muscle Hypotonia ; Tay-Sachs Disease* ; Tracheostomy

Tay-Sachs disease (GM2 gangliosidosis, type 1; TSD) is an autosomal recessive GM2 gangliosidosis resulting from the deficient activity of the lysosomal hydrolase beta-hexosaminidase A (Hex A). With a carrier frequency estimated at 1 in 25, it is a common lysosomal disorder in the Ashkenazi Jewish population. Tay-Sachs disease has provided the prototype for the prevention of severe recessive genetic diseases. Molecular analysis of the Hex A gene (HEXA) of Ashkenazi Jewish individuals affected with Tay-Sachs disease revealed that three common mutations cause the infantile and adult onset forms of the disease; a four base insertion in exon 11, a splice junction mutation in intron 12 and a point mutation in exon 7 (G269S). A study was undertaken to determine whether mutation analysis would be useful in TSD screening programs in identifying carriers and clarifying the status of individuals whose enzyme assays are inconclusive. Ashkenazi Jewish individuals who had been diagnosed as carriers, inconclusives by enzyme assay and non-carriers with low normal enzyme levels in the Mount Sinai Tay-Sachs Disease Prevention Program were examined for the presence of the three mutations using polymerase chain reaction (PCR) and allele specific oligonucleotide (ASO) hybridization. The insertion mutation was present in 29 of 34 carriers and 2 of 36 inconclusive individuals, the splice junction mutation was found in 4 of 34 carriers and the G269S mutation was found in 1 of 34 carriers. Of the 313 non-carrier individuals with normal enzyme activity in the lower normal range, one was positive for the splice junction mutation.(ABSTRACT TRUNCATED AT 250 WORDS)
Base Sequence ; *Clinical Enzyme Tests ; DNA/*analysis ; *Genetic Testing ; *Heterozygote ; Heterozygote Detection ; Humans ; Molecular Sequence Data ; Mutation ; Tay-Sachs Disease/*genetics

Tay-Sachs disease is an autosomal recessive, neurodegenerative disorder that results from excessive storage of the cell membrane glycolipid, and GM2 ganglioside within the lysosomes of cells. This disease is caused by deficiency of the isoenzyme beta-hexosaminidase A, produced in the endoplasmic reticulum. Patients with Tay-Sachs disease are characterized by normal motor development in the first few months of life, followed by progressive weakness and loss of motor skills beginning around 2 to 6 months of life. Neurodegeneration is relentless, with death occurring by the age of 4 or 5 years. Tay-Sachs disease could be diagnosed by hexosaminidase enzyme assay and DNA analysis of HEXA gene. However, specific treatment has not been developed. We report here on a case of Tay- Sachs disease in 18-month-old male who presented with delayed development and seizure. This patient showed hyperacusis and cherry red spot in macula on examination of the fundus. The hexosaminidase A activity was zero percent in the enzymatic assay and DNA analysis identified a mutation that glutamine is substituted by stop codon at position 390(Q390X). This patient is the first case of Tay-Sachs disease in Korea diagnosed by enzymatic assay and DNA analysis.
beta-N-Acetylhexosaminidases ; Cell Membrane ; Codon, Terminator ; DNA* ; Endoplasmic Reticulum ; Enzyme Assays* ; G(M2) Ganglioside ; Glutamine ; Hexosaminidase A ; Hexosaminidases ; Humans ; Hyperacusis ; Infant ; Korea* ; Lysosomes ; Male ; Motor Skills ; Neurodegenerative Diseases ; Prunus ; Seizures ; Tay-Sachs Disease*