Sandhoff Disease – Type I
Etiology and Pathogenesis [1]Results from defect in the beta chain of beta-hexosaminidase. Beta-hexosaminidase A isoenzyme contains an alpha and a beta chain, and beta-hexosaminidase B isoenzyme contains two beta chains, therefore Sandhoff disease affects both isoenzymes. (By comparison, Tay-Sachs disease, which results from an alpha-chain defect, affects only A isoenzyme.) Enzyme deficiency results in accumulation of GM2 gangliosides and globosides in the central nervous system and peripheral tissues. Key Symptom Images
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Hepatosplenomegaly |
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Image Credits: Cherry-red macular spots courtesy of Jay M. Haynie, OD.
Clinical Description and Progression/Prognosis [1]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. May include involvement of bones and abdominal organs. With the infantile form:  Normal development up to 3-6 months of age Onset of developmental delay followed by rapid regression by the end of 1st year of life Inheritance pattern: autosomal recessive Incidence: 1 in 384,000 live births (for types I and II together) [2] Diagnosis: enzyme assay of serum or leukocytes to demonstrate absence/near absence of total beta-hexosaminidase activity; presence of PAS-positive materials in systemic tissue to distinguish from Tay-Sachs and GM2 activator deficiency. Conditions with similar presentations: Tay-Sachs Management: no disease-specific treatment available Other medical care: symptom management
Progressive hypotonia with motor weakness Poor head control Failure to turn over, crawl, or sit Assumes a frog-like position Eventually becomes hypertonic with exaggerated reflexes Social/behaviora issues: Decreasing eye contact and focusing Interacts very little with environment, eventually becoming unresponsive to exogenous stimuli reaching vegetative state Seizures - Commonly begin after 1st year of life and vary in type and frequency Hyperacusis - Initially an exaggerated startle response to sharp sounds, eventually becoming inattentive and unresponsive* 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 Blindness by the 2nd year of life Unusual eye movements Hepatosplenomegaly Bony dysplasias Back to categories
1. Hauser SL, Longo DL, eds. Harrison’s Principles of Internal Medicine. 14th ed. New York: McGraw-Hill; 1998; p. 2171.
2. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of Lysosomal Storage Disorders. JAMA. 1999; 281: 249-254.
3. Gravel, Roy et al. “The GM2 Gangliosidoses: Sandhoff Disease and Variants.” The Metabolic and Molecular Bases of Inherited Disease, 8th Edition Online. McGraw-Hill. http://genetics.accessmedicine.com/server-java/Arknoid/amed/mmbid/co_chapters/ch153/ch153_p21.html?searchterm=sandhoff;
Accessed September 2004.
* Unique to Sandhoff’s disease per table in Harrison’s, Chapter 349. |
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