Sandhoff disease

Sandhoff disease (also Sandhoff 's disease, according to Konrad Sandhoff or Sandhoff Jatzkewitz 's disease) is a rare autosomal recessive lysosomal storage disease belonging to the group of Sphingolipidoses. It is a progressive neurodegenerative disorder in which there is an accumulation of GM2 ganglioside in particular in nerve cells.

Aetiology and prevalence

Sandhoff disease is caused by a mutation of HEXB gene on chromosome 5 locus. This gene codes for the β - subunit of the enzyme hexosaminidase A and B. Accordingly, when a mutation affects both enzymes. The hexosaminidase in the cells catalyze the degradation of GM2 gangliosides. By the limited enzyme activity leads to an accumulation of GM2 ganglioside. These are especially affected nerve cells.

Sandhoff disease is an autosomal recessive trait. In contrast to Tay- Sachs disease both hexosaminidase A and B are affected; the Tay- Sachs disease only the hexosaminidase A.

The prevalence in Europe is approximately 1:130.000.

Symptoms and Diagnosis

Clinically, the disease in its symptoms is almost indistinguishable from Tay- Sachs disease, except that ethnicity plays only a very minor role. In the first three to six months of life, the affected children develop normally at first. Then they show - as in Tay- Sachs disease - startle responses to sound stimuli, a cherry-red spot on the macula and a larger than average head ( macrocephaly ), as a result of gliosis. In the further course of the disease it comes to blindness. The mental and motor deterioration is progressive.

The reduced activity of the hexosaminidase A and B, can be demonstrated in fibroblasts and leukocytes, as well as in serum. DNA analysis is possible, but usually not necessary. In the urine The content of oligosaccharides is greatly increased.

Treatment and prognosis

There is no causal therapy for the treatment of Sandhoff disease. Treatment is usually symptomatic. Some therapeutic approaches are still in early development phases.

The prognosis is unfavorable. Affected children usually die at the age of about four years.

First description

Sandhoff 's disease was first described in 1968 by the German biochemist Konrad Sandhoff, the so became the namesake of this disease.