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 II, 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).

Cherry-red macular spots

Image Credits: Cherry-red macular spots courtesy of Jay M. Haynie, OD.

Early blindness, progressive mental and motor deterioration, doll-like face, cherry-red macular spots, and enlargement of the heart. Loss of swallowing function occurs progressively, with increased risk for aspiration and subsequent chest and lung infections. Bones or peripheral organs are not involved.

Normal development up to 3-6 months of age

Onset of developmental delay, loss of motor skills, seizures, and blindness[3] followed by rapid regression by the end of 1st year of life

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 presentation: Gaucher disease, GM1 gangliosidosis, galactosialidosis, Niemann-Pick disease type A, Sandhoff disease, other rare neurodegenerative diseases such as Krabbé, Canavan, or Alexander disease^[2]

Management: no disease-specific treatment available

Other medical care: symptom management

Progressive hypotonia and motor weakness

Poor head control

Failure to turn over, crawl, or sit

Assumes a frog-like position

Eventually becomes hypertonic with exaggerated reflexes

Social/behavioral:

Decreasing eye contact and focusing

Interacts very little with environment, eventually becoming unresponsive to exogenous stimuli and reaching vegetative state

Hyperacusis - Initially an exaggerated startle response to sharp sounds, eventually becoming inattentive and unresponsive

Seizures - Commonly begin after 1st year of life and vary in type and frequency

Macrocephaly - Commonly by 1.5 to 2 years of age due to a reactive cerebral gliosis

Cherry-red macular spots (prominent macular fovea centralis)

Progressive visual inattention with blindness by the 2nd year of life

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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.