Sandhoff disease is a lipid storage disorder characterized by a progressive deterioration of the central nervous system. The clinical symptoms of Sandhoff disease are identical to Tay-Sachs disease. Sandhoff disease is an autosomal recessive genetic disorder caused by an abnormal gene for the beta subunit of the hexosaminidase B enzyme. This gene abnormality results in a deficiency of hexosaminidase A and B that results in accumulation of fats (lipids) called GM2 gangliosides in the neurons and other tissues.
The first symptoms of the infantile form of Sandhoff disease typically begin between the ages of 3 to 6 months. These may include feeding problems, general weakness (lethargy), and an exaggerated startle reflex in response to sudden loud noises. A physician’s examination with a special instrument typically reveals round, red spots (cherry macules) in the eyes. Motor delays and mental deterioration are progressive and are characterized by motor weakness, spasticity, heart murmurs, seizures (myoclonic and generalized), blindness, and/or abnormally enlarged spleen (splenomegaly). Firm stroking of the sole of the foot produces a typical reflex response (Babinski sign), and the outer toes spread after the side of the sole of the foot has been stroked.
Juvenile and adult forms of Sandhoff disease have been described that are more variable in the age of onset and severity of symptoms.
Sandhoff disease is an autosomal recessive genetic disorder caused by an abnormal gene for the beta subunit of the hexosaminidase B (HEXB) enzyme. This gene abnormality results in a deficiency of enzymes called hexosaminidase A and B that are responsible for breaking down GM2 gangliosides made by the nerve cells. The accumulation of GM2 gangliosides in the lysosomes of nerve cells damages the nerve cells and leads to a progressive loss of neurological function.
Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Sandhoff disease is a very rare disorder that affects males and females in equal numbers. This disorder occurs in people of many different ethnic backgrounds. Sandhoff disease may be more common in the Creole population of northern Argentina, the Metis Indians in Saskatchewan, Canada and individuals of Lebanese ancestry.
Sandhoff disease can be diagnosed by performing an enzyme assay to determine activity of the hexosaminidase A and B enzymes. Affected individuals have absent or reduced activity of both enzymes. Molecular genetic (DNA) testing is available to determine the specific gene mutation that is present in the beta subunit of the Hexosaminidase B gene and confirm the diagnosis.
Treatment of Sandhoff disease is symptomatic and supportive and includes nutritional and respiratory therapy. Anticonvulsants may be prescribed to temporarily control seizures. Death from respiratory infection usually occurs by age three for the infantile form of the disease.
Genetic counseling is recommended for affected individuals and their families.
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MacLeod PM, Wood S, Jan JE, et al. Progressive cerebral ataxia, spasticity, psychomotor retardation, and hexosaminidase deficiency in a 10 year-old child: juvenile Sandhoff disease. Neurology 1977;27:571-573.
Rubin M, Karpati G, Wolfe LS, et al. Adult onset motor neuropathy in the juvenile type of hexosaminidase A and B deficiency. J Neurol 1988:87:103-119.
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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No. 268800: Last Update:9/1/05.
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