Metabolic defect: beta-hexosaminidase (alpha chain) deficiency Other sphingolipid degradation diseases: acid sphingomyelinase deficiency | Fabry | Farber | Gaucher: type I, type II, type III | GM1 gangliosidosis: type I, type II, type III | Tay-Sachs: type I, type III | Sandhoff: type I | Krabbé | metachromatic leukodystrophy: type I, type II, type III

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Results from a defect in the alpha chain of beta-hexosaminidase. Beta-hexosaminidase A isoenzyme contains an alpha and a beta chain (beta-hexosaminidase B isoenzyme contains two beta chains); Tay-Sachs affects only the A isoenzyme. (By comparison, Sandhoff disease, which results from a beta-chain defect, affects both isoenzymes.) Enzyme deficiency results in accumulation of GM2 gangliosides in the central nervous system. The infantile form has a complete deficiency of beta-hexosaminidase activity (other forms have a partial deficiency).

Ataxia/choreoathetoid movements				Retinitis pigmentosa (late in course)

Image Credits: Retinitis pigmentosa courtesy of John A. Moran Eye Center, University of Utah.

Juvenile form begins with ataxia and loss of coordination between 2 and 10 years of age. Speech, cognition, and other motor skills deteriorate, generally followed by seizures and spasticity by end of the 1st decade. Compared with the infantile form, loss of vision progresses much more slowly and the cherry-red spot is not homogenous. Death is usually due to infection.

Inheritance pattern: autosomal recessive

Incidence: pan-ethnic, but higher frequency among Ashkenazi Jews^[3]; 1 in 201,000 live births (for types I, II, and III together)^[4]

Diagnosis: enzyme assay

Conditions with similar presentations: juvenile neuronal ceroid lipofuscinosis (Batten disease), Sandhoff disease^[2]

Management: no disease-specific treatment available

Other medical care: symptom management

Progressive ataxia, choreoathetosis, and dysarthria

Progressive spasticity leading to decerebrate rigidity by 10-12 years of age

Progressive dementia leading to a vegetative state

Seizures

1. Hauser SL, Longo DL, eds. Harrison’s Principles of Internal Medicine. 14th ed. New York: McGraw-Hill; 1998; p. 2171.

2. Kaback, Michael M, MD. “Hexosaminidase A Deficiency.” www.genetests.org. Updated 9 January 2004.

3. University of Pittsburgh, Lysosomal Disease Center. www.pitt.edu/AFShome/g/e/geneorb/public/html/courses/lyso_trials/gm2.html Accessed July 2004.

4. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of Lysosomal Storage Disorders. JAMA. 1999; 281: 249-254.