Sandhoff disease

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Classification according to ICD-10
E75.0 GM2 gangliosidosis
Sandhoff disease
ICD-10 online (WHO version 2019)

The Sandhoff disease (including Crohn's Sandhoff , to Konrad Sandhoff or Sandhoff Jatzkewitz's disease ) is a very rare autosomal - recessive inherited lysosomal storage disease from the group of sphingolipidoses . It is a progressive running neurodegenerative disease , it in an accumulation of GM2 ganglioside specifically in nerve cells comes.

Etiology and prevalence

Sandhoff disease is caused by a mutation in the HEXB gene on chromosome 5 gene locus . This gene codes for the β-subunit of the enzymes hexosaminidase A and B. As a result, both enzymes are affected in the event of a mutation. The hexosaminidases catalyze the breakdown of GM2 gangliosides in the cells . The restricted enzyme activity leads to an accumulation of GM2 gangliosides. This particularly affects the nerve cells.

Sandhoff disease is inherited as an autosomal recessive trait. In contrast to Tay-Sachs syndrome , both hexosaminidases A and B are affected; in Tay-Sachs syndrome only hexosaminidase A.

The prevalence in Europe is around 1 in 130,000.

Symptoms and diagnosis

Clinically, the disease is in their symptoms almost from Tay-Sachs disease to distinguish, except that the only ethnic group plays a very minor role. In the first three to six months of life, the affected children initially develop normally. Then they show - as in Tay-Sachs syndrome - startle reactions to sound stimuli , a cherry-red spot on the macula and a larger than average skull ( macrocephaly ) as a result of gliosis . As the disease progresses, blindness occurs . The mental and motor decline are progressive.

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

Therapy and prognosis

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

The prognosis is poor . The affected children usually die around the age of four.

Initial description

Sandhoff's disease was first described in 1968 by the German biochemist Konrad Sandhoff , who gave the disease its name.

Individual evidence

  1. ^ Sandhoff disease.  In: Online Mendelian Inheritance in Man . (English), accessed January 11, 2009.
  2. ↑ SK Srivastava and E. Beutler: Hexosaminidase-A and hexosaminidase-B: studies in Tay-Sachs' and Sandhoff's disease. In: Nature 241, 1973, p. 463. PMID 4122341
  3. ^ Sandhoff disease. In: Orphanet (Rare Disease Database). , accessed January 11, 2009.
  4. ↑ SK Tay et al: Sandhoff disease - a case report of 3 siblings and a review of potential therapies. In: Ann Acad Med Singapore 29, 2000, pp. 514-517. PMID 11056783
  5. ↑ M. Jeyakumar et al .: Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin. In: PNAS 96, 1999, pp. 6388-6393. PMID 10339597
  6. ↑ K. Sandhoff et al: Deficient hexosaminidase activity in an exceptional case of Tay-Sachs disease with additional storage of kidney globoside in visceral organs. In: Life Sci 7, 1968, pp. 283-288. PMID 5651108 .
  7. ↑ K. Sandhoff et al.: Enzyme alterations and lipid storage in three variants of Tay-Sachs disease. In: J. Neurochem. 18, 1971, pp. 2469-2489. PMID 5135907

literature

Reference books

  • J. Cervós-Navarro and others: Special pathological anatomy. Verlag Springer, 1991, ISBN 3-540-52873-3 , pp. 333-340.
  • B. Kirchhof and others: diagnoses at the fundus. Georg Thieme Verlag, 2003, ISBN 3-13-125641-9 , p. 99.

Review article

  • CJ Hendriksz: Juvenile Sandhoff disease - nine new cases and a review of the literature. In: J Inherit Metab Dis 27, 2004, pp. 241-249. PMID 15159655
  • H. Schnorf: Adult form of GM2-gangliosidosis: a man and 2 sisters with hexosaminidase-A and -B deficiency (Sandhoff disease) and literature review. In: Schweiz Med Wochenschr 126, 1996, pp. 757–764. PMID 8693300

Technical article

  • H. Jatzkewitz and K. Sandhoff: Sphingolipid storage diseases as an example of a molecular neuropathology. In: European Archives of Psychiatry and Clinical Neuroscience 221, 1976, pp. 213-225. doi : 10.1007 / BF00418481
  • PA Bolhuis et al: Ganglioside storage, hexosaminidase lability, and urinary oligosaccharides in adult Sandhoff's disease. In: Neurology 37, 1987, pp. 75-81. PMID 2948136
  • MA McNally et al .: Peripheral nervous system manifestations in a Sandhoff disease mouse model: nerve conduction, myelin structure, lipid analysis. In: J Negat Results Biomed 10, 2007, pp. 6-8. PMID 17623103
  • R. Wada et al .: Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation. In: PNAS 97, 2000, pp. 10954-10959. PMID 11005868
  • RM Cantor et al .: Sandhoff disease heterozygous detection: a component of population screening for Tay-Sachs disease carriers. II. Sandhoff disease gene frequencies in American Jewish and non-Jewish populations. In: Am J Hum Genet 41, 1987, pp. 16-26. PMID 2955697

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