written by: bjlbyron•edited by: lrohner•updated: 6/27/2011
Sandhoff Disease is an inherited disorder of the central nervous system that often results in death in infancy or early childhood. This article describes both this condition and its underlying genetic cause.
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What Is Sandhoff Disease?
Sandhoff Disease (SD) is a genetic disorder which is marked by the steady deterioration of the nerve cells in the brain and spinal cord (i.e., central nervous system). SD, which is a severe variant of Tay-Sachs disease, typically first presents at about 3 to 6 months of age. SD symptoms include physical weakness (for example, infants usually have difficulty crawling, rolling over and sitting upright), blindness or other eye and vision problems, mental retardation or other severe mental disability, an unusually enlarged head, enlarged organs, seizures, bone defects, and overreaction to sound (easily startled). A hallmark characteristic of SD is the appearance of a bright red spot on the eye which can be detected readily through routine eye examination.
In a limited number of cases, SD has first presented later in life, such as later in childhood or even in adulthood. Individuals who first experience SD-caused symptoms later in life typically suffer from a milder form of SD than do those who are stricken during infancy.
No matter at what age SD symptoms first arise, treatment options are limited. The typical treatment course is to keep the affected individual well-fed and hydrated, to keep the airways open, and to provide anticonvulsants to help treat seizures. Sadly, most individuals who are inflicted with SD die prior to age three. In many cases, death is due to respiratory infection. While SD can strike people of any background, it is more commonly seen in people from Canada (and Saskatchewan in particular), Argentina, and Lebanon than it is in other parts of the world.
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What Is Known About The Genetic Cause of Sandhoff Disease?
Human molecular geneticists have determined that mutations in a gene that is designated HEXB are causative of SD. The HEXB gene encodes a protein that forms a portion of two other proteins, which are referred to as beta-hexosaminidase A and beta-hexosaminidase B. These two proteins act within cellular structures that are known as lysosomes. In lysosomes, these proteins act to break down fatty acids, complex sugars, and other compounds. Further, beta-hexosaminidase A helps to break down a compound that is referred to as GM2 ganglioside.
People who have one or more mutations in both copies of their HEXB gene cannot make fully functional beta-hexosaminidase A and beta-hexosaminidase B. As a result, these individuals are unable to break down the compounds described above. These compounds therefore accumulate in the body, and in the neurons in particular. Build up of these compounds, especially GM2 ganglioside, leads to the progressive wasting of neurons, which is characteristic of SD and leads to its symptoms.
This article is only meant to provide some basic information regarding the genetic condition known as Sandhoff Disease. If you have any further questions regarding this inherited disorder, please contact your doctor or consult a genetic counselor.