Updated: 3/13/2017

Tay-Sachs Disease

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Snapshot
  • An 8-month-old boy of central European descent is brought to the pediatrician due to progressive weakness, decreased visual attentiveness, and an exaggerated response when startled. He was born at 38 weeks gestation with no perinatal complications and an unremarkable prenatal history. At birth, he had no apparent deficits. On physical examination, there is no hepatosplenomegaly. On fundoscopy, there is a prominent fovea centralis, accompanied by pallor of the perifoveal macula. Laboratory testing is significant for 1% β-hexosaminidase A activity with normal β-hexosaminidase B isoenzyme activity in white blood cells.
Introduction
  • Clinical definition
    • lysosomal storage disorder secondary to hexosaminidase A deficiency
  • Epidemiology
    • incidnce
      • Ashkenazi Jews are mostly affected
    • location
      • where in the body/bone
    • risk factors
      • Ashkenazi Jewish descent
      • family history of hexosaminidase A deficiency
  • Pathophysiology
    • pathobiology
      • normally, hexosaminidase A breaks down GM2 ganglioside
        • enzyme deficiency results in ganglioside accumulation within the lysosome of nerve cells resulting in neurodegeneration
  • Genetics
    • inheritance pattern
      • autosomal recessive
    • mutations
      • chromosome 15
      • α subunit of hexosaminidase A (HEXA) gene
        • protein encoded for hexosaminidase A
  • Prognosis
    • in infantile-type of Tay-Sachs disease (TSD) leads to death before 5 years of age
    • in juvenile-type TSD, death typically occurs in adolescence or late childhood
    • in late-onset type of TSD, there is long-term survival
Presentation
  • Symptoms
    • dependent on the type of TSD
      • progressive weakness
      • hypotonia
      • seizures
      • vision loss
      • ataxia/incoordination
      • cognitive impairment
  • Physical exam 
    • dependent on the type of TSD
      • cherry red spot of fovea centralis of macula  
      • hyperreflexia
      • decerebrate posturing
      • liver and spleen are normal sized
Studies
  • Diagnostic criteria
    • diagnosis is confirmed with absent-to-near absent β-hexosaminidase A acitivity
      • this can be performed in white blood cells and serum
      • β-hexosaminidase B isoenzyme must be normal or elevated
    • molecular genetic testing of beta-hexosaminidase A is useful for
      • genetic counseling in at-risk family members
Differential
  • Krabbe disease
  • Gaucher disease
  • Metachromatic leukodystrophy
Treatment
  • Conservative
    • supportive treatment
      • indications
        • in patients with TSD because there is no disease-modifying therapy
Complications
  • Infection
  • Poor weight gain
  • Falls

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