Sandhoff disease is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, its derivative GA2, the glycolipid globoside in visceral tissues, and some oligosaccharides. Accumulation of these metabolites leads to a progressive destruction of the central nervous system and eventually to death. The rare autosomal recessive neurodegenerative disorder 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. Symptoms and signs
Sandhoff disease symptoms are clinically indeterminable from Tay–Sachs disease. The classic infantile form of the disease has the most severe symptoms and is incredibly hard to diagnose at this early age. The first signs of symptoms begin before 6 months of age and the parents’ notice when the child begins regressing in their development. If the children had the ability to sit up by themselves or crawl they will lose this ability. This is caused by a slow deterioration of the muscles in the child’s body from the buildup of GM2 gangliosides. Since the body is unable to create the enzymes it needs within the central nervous system, it is unable to attach to these gangliosides to break them apart and make them non-toxic.
The patient also lacks the ability to cough and therefore must undergo a treatment to shake up their body to remove the mucus from the lining of their lungs. Medication is also given to patients to lessen their symptoms including seizures.Currently the government is testing several treatments including N-butyl-deoxynojirimycin in mice, as well as stem cell treatment in humans and other medical treatments recruiting test patients. A Sandhoff disease study showing proof of principle for gene therapy in a human model system using CRISPR and virus gene correction gives the chance for clinical trials to cure the disease. The ultra-rare occurrence is a main hurdle to overcome for clinical trials. History
Sandhoff disease is one of several forms of what was formerly known as amaurotic idiocy. This inherited disease is characterized by the accumulation of lipid-containing cells in the viscera and in the nervous system, mental retardation, and impaired vision or blindness. The chemical and enzymatic analysis of various patients with amaurotic idiocy by Konrad Sandhoff (1939- ), a German biochemist, led to the identification of several biochemically distinct diseases: The first biochemical description of GM1-gangliosidosis in 1963, Sandhoff disease in 1968, Tay-Sachs-Disease, the AB-variant of GM2-Gangliosidosis and the B1-variant of GM2-gangliosidosis.The molecular defect in Sandhoff disease was discovered when Konrad Sandhoff studied the biochemistry of sphingolipids and gangliosides in the laboratory of Prof. Horst Jatzkewitz (1912–2002), a German biochemist (Max- Planck-Institute for Psychiatry, Munich). In October 1966, he obtained deep-frozen autopsy material from an infantile case with amaurotic idiocy.