WHAT IS SANDHOFF?
Sandhoff disease is very similar to Tay-Sachs but the defected gene, called HEXB, does not allow the production of two enzymes (beta-hexosaminidase A and beta-hexosaminidase B). The disease also results in premature death in a sufferer and the signs and symptoms are the same as in Tay-Sachs.
WHAT CAUSES SANDHOFF?
Mutations in the HEXB gene causes Sandhoff disease. The gene provides instructions for making a protein crucial to the enzymes Hex-A and Hex-B which function in nerve cells to break down fatty substances, complex sugars, and molecules that are linked to sugars. In particular, Hex-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 and other molecules. As a result, progressive damage caused by the resulting buildup of GM2 leads to the destruction of nerve cells.
SYMPTOMS OF SANDHOFF
Sandhoff disease symptoms are clinically very similar to Tay-Sachs. The classic infantile form of the disease has the most severe symptoms and is incredibly hard to diagnose at an early age. Adult and juvenile forms of Sandhoff disease are more rare then the infantile form and in these cases individuals suffer cognitive problems and a loss of muscle coordination that eventually destroys their ability to walk. As in Tay-Sachs, younger suffers of Sandhoff have a limited life expectancy as the disease progresses.
THE VARIANTS OF SANDHOFF
As a rare autosomal recessive neurodegenerative disorder, Sandhoff is clinically almost indistinguishable from Tay–Sachs disease, another genetic disorder that disrupts beta-hexosaminidases A and S. There are three subsets of Sandhoff disease based on when first symptoms appear: classic infantile, juvenile and adult late onset.
In Classic Infantile the destructive process begins in the fetus early in pregnancy, although the disease is not clinically apparent until the child is several months old. By the time a child with Tay-Sachs disease is three or four-years old, the nervous system is so badly affected that life itself cannot be supported. Even with the best of care, all children with classic Tay-Sachs disease die early in childhood, usually by the age of 5, although some do live longer.
Children with Juvenile Tay-Sachs usually develop symptoms between the ages of 2 and 5 that resemble the symptoms of the Classic Infantile form. Though the course of the disease is slower, end stages generally occur in late adolescence or into the 20s. If starting after age 5, symptoms may be milder than those that characterize earlier onset forms. Mental abilities, vision and hearing remain intact, but affected individuals develop ataxia (lack of coordination), dysarthria (slurred speech), muscle atrophy (weakness), tremors and unsteady gait.
Late Onset or Chronic Tay-Sachs’ symptoms typically presents in adolescence, with dysarthria, proximal (trunk) muscle weakness, tremor and ataxia. Muscle cramps, especially in the legs at night, and fasciculations (muscle twitching) are common. Not all symptoms are present in every individual affected by the disease; weakness of the proximal muscles, however, is a symptom common to all. Examples of trunk muscle weakness may include difficulty rising from a seated position, trouble getting out of bed, struggling to balance while getting dressed.
Sadly, there is currently no cure for Tay-Sachs or its associated diseases. Children affected with Tay-Sachs have no hope unless we help raise funds to aid the research on the way. A cure for Tay-Sachs will also mean a cure for over 70 other Lysosomal Storage Diseases as well as other neurological conditions such as Parkinson’s, Alzheimer’s and Multiple-Sclerosis.