A. Introduction

1. Lysosomal sphingolipid storage disroder
2. Autosomal recessive inheritance
3. Usually infants of central or eastern European Jews (Ashkenazi)

B. Biochemstry and Pathology
[Figure] "Sphingolipid Storage Diseases"

1. Accumulation of GM2 Ganglioside
   1. Due to profound deficiency of lysosomal hydrolase ß-hexosaminidase A
   2. Catalyzes cleavage of terminal ß-linked N-acetylgalactosamine from GM2 Ganglioside
2. Neuronal Changes
   1. Accumulation of GM2 Ganglioside in neuronal lysosomes
   2. Ballooning of neurons
   3. Lipophilic membranous bodies (composed of GM2 Ganglioside)

C. Symptoms

1. Hypotonia
2. Blindness
3. Dementia
4. Seizures
5. Death occurs age 3-5 years

D. Screening [1]

1. No treatment currently available
2. Carrier screening is highly effective method for prevention
3. Screening error rates <2% (extremely rare after 1988)
4. Amniocentesis or chorionic villus sampling can also be done

References

1. Kaback M, Lim-Steele J, Dabholkar D, et al. 1993. JAMA. 270(19):2307