Last updated 2mo ago
A 6-month-old of Ashkenazi Jewish ancestry has developmental regression, exaggerated startle response, and cherry-red spot on fundoscopy. Hexosaminidase A is deficient.
AR; HEXA (hexosaminidase A)
- Common in Ashkenazi Jewish, French Canadian, Cajun populations
- GM2 ganglioside accumulation
- Normal at birth, regression begins 3-6 months
- Cherry-red spot on macula
- Exaggerated startle response
- Progressive neurodegeneration, blindness, seizures
- Macrocephaly
- Death by 4-5 years
Carrier Screening: Enzyme assay or DNA testing for at-risk populations
- Deficient hexosaminidase A enzyme activity in serum or leukocytes (with normal/elevated total hexosaminidase, reflecting preserved Hex B)
- HEXA molecular testing confirms the diagnosis and resolves pseudodeficiency alleles that lower enzyme activity without causing disease
- Cherry-red macula on fundoscopy supports the clinical picture
- No disease-modifying therapy; supportive and palliative care
- Anticonvulsants for seizures, nutritional support for dysphagia, secretion management
- Genetic counseling and carrier screening for at-risk populations; prenatal/preimplantation testing options
tAy sAchs = hexA: Tay-Sachs is caused by deficiency of hexosaminidase A (the "A" appears in both "tAy" and "sAchs"). Compare with Sand-hoff = hexB ("get the Sand off at the Beach").
Tay-Sachs has a Typical Spleen: no hepatosplenomegaly (vs. Niemann-Pick, which has a Massive sPleen). Both have a cherry-red spot on the macula.
GM2 ganglioside: 2 words, 2 syllables (Tay-Sachs): GM2. "Ganglioside" makes you think of ganglia/neurons: only neurons are affected. Death by age 4 years; exaggerated startle response ("Taylor Swift is a star").