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 Incidence Ashkenazi Jews are mostly affected Location where in the body/bone Risk factors Ashkenazi Jewish descent family history of hexosaminidase A deficiency ETIOLOGY 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 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 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