Sandhoff disease is a rare inherited disorder that causes progressive destruction of nerve cells in the brain and spinal cord. Jump to: navigation, search A nerve is an enclosed, cable-like bundle of nerve fibers or axons, which includes the glia that ensheath the axons in myelin. ... Jump to: navigation, search In the anatomy of animals, the brain, or encephalon, is the higher, supervisory center of the nervous system. ... Jump to: navigation, search The spinal cord is a part of the vertebrate nervous system that is enclosed in and protected by the vertebral column (it passes through the spinal canal). ...

The most common and severe form of Sandhoff disease begins in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 months, when development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. As the disease progresses, infants develop seizures, vision and hearing loss, mental retardation, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Some infants with Sandhoff disease may also have enlarged organs (organomegaly) or bone abnormalities. Children with the severe form of this disorder usually live only into early childhood. Jump to: navigation, search A top-down view of skeletal muscle Muscle is a contractile form of tissue. ... A motor skill is a skill required for proper usage of skeletal muscles. ... Jump to: navigation, search Mental retardation (also called mental handicap and, as defined by the UK Mental Health Act (1983), mental impairment and severe mental impairment) is a term for a pattern of persistently slow learning of basic motor and language skills (milestones) during childhood, and a significantly below-normal... Paralysis is the complete loss of muscle function for one or more muscle groups. ... Jump to: navigation, search This article needs to be cleaned up to conform to a higher standard of quality. ... Organomegaly Abnormal enlargement of organs, for example heart, liver etc. ...

Other forms of Sandhoff disease are very rare. Signs and symptoms can begin in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form of Sandhoff disease. As in the infantile form, mental abilities and coordination are affected. Characteristic features include muscle weakness, loss of muscle coordination (ataxia) and other problems with movement, speech problems, and mental illness. These signs and symptoms vary widely among people with late-onset forms of Sandhoff disease. Ataxia (from Greek ataxiā, meaning failure to put in order) is unsteady and clumsy motion of the limbs or trunk due to a failure of the fine coordination of muscle movements. ...

Mutations in the HEXB gene cause Sandhoff disease. The HEXB gene provides instructions for making a protein that is part of two critical enzymes in the nervous system. These enzymes, beta-hexosaminidase A and beta-hexosaminidase B, function in nerve cells to break down fatty substances, complex sugars, and molecules that are linked to sugars. In particular, beta-hexosaminidase A breaks down a fatty compound called GM2 ganglioside. Mutations in the HEXB gene disrupt the activity of these enzymes, preventing the breakdown of GM2 ganglioside and other molecules. As a result, these compounds can accumulate to toxic levels within cells. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of nerve cells, which causes the signs and symptoms of Sandhoff disease. The condition is inherited in an autosomal recessive pattern. Jump to: navigation, search This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ...

Sandhoff disease is a rare disorder; its frequency varies among populations. This condition appears to be more common in the Creole population of northern Argentina; the Metis Indians in Saskatchewan, Canada; and people from Lebanon.

See also

• Tay-Sachs disease
• GM2-gangliosidosis, AB variant

This article incorporates public domain text from The U.S. National Library of Medicine Tay-Sachs disease (abbreviated TSD) is a fatal genetic disorder, inherited in an autosomal recessive pattern, in which harmful quantities of a fatty substance called ganglioside GM2 accumulate in the nerve cells in the brain. ...