pediatrics
Tay Sachs Disease and Sandhoff Disease
Tay Sachs disease
Deficiency of hexosaminidase A results in accumulation of GM2 in the brain. Inheritance is Autosomal Recessive ; the most common mutations are carried by 1/27 normal adults of Eastern European (Ashkenazi) Jewish origin, although other mutations cluster in some French-Canadian and Cajun populations. Children with Tay-Sachs disease start missing developmental milestones after age 6 months and develop progressive cognitive and motor deterioration resulting in seizures, intellectual disability, paralysis, and death by age 5 years. A cherry-red macular spot is common. Diagnosis of Tay-Sachs disease is clinical and can be confirmed by DNA analysis and/or enzyme assay. (Also see Initial testing .) In the absence of effective treatment, management is focused on screening adults of childbearing age in high-risk populations to identify carriers (by way of enzyme activity and mutation testing) combined with genetic counseling. 