Foundations · Year 1 · from Foundations
Case 1: Tay-Sachs Disease (Lysosomal Storage Disorder)
Clinical Image
Source: Wikipedia - Tay-Sachs disease - CC BY-SA 3.0
Case Presentation
A 6-month-old infant of Ashkenazi Jewish descent is brought to the pediatrician by concerned parents who notice their previously developmentally normal child has become increasingly listless and shows an exaggerated startle response to sounds. Physical examination reveals hypotonia and decreased visual tracking. Ophthalmologic examination shows the pathognomonic cherry-red spot on the macula, caused by lipid accumulation in retinal ganglion cells surrounding the fovea. Genetic testing confirms homozygous mutations in the HEXA gene, encoding the alpha subunit of hexosaminidase A. Without functional hexosaminidase A, GM2 ganglioside accumulates in lysosomes, particularly in neurons, leading to progressive neurodegeneration. The diagnosis is infantile Tay-Sachs disease. The family is counseled that there is no curative treatment and the condition is fatal, typically by age 4. Supportive care, genetic counseling for the family, and connection with support resources are provided.
Key Learning Points
- Tay-Sachs disease exemplifies lysosomal storage disorders caused by deficiency of lysosomal hydrolases leading to substrate accumulation
- The cherry-red spot results from normal fovea (lacking ganglion cells) surrounded by pale, lipid-laden ganglion cells - a classic finding on fundoscopic exam
- Carrier screening is recommended for Ashkenazi Jewish populations (carrier frequency ~1 in 30) and has dramatically reduced disease incidence