Tay-Sachs syndrome
| Classification according to ICD-10 | |
|---|---|
| E75.0 | GM 2 gangliosidosis Tay-Sachs disease |
| ICD-10 online (WHO version 2019) | |
The Tay-Sachs disease , also under the names Crohn Tay-Sachs , Tay-Sachssche disease and infantile amaurotic idiocy known (congenital severe mental retardation with blindness) is an autosomal -rezessiv inherited with disease Sandhoff to the GM 2 -Gangliosidosen with Lipid metabolism disorder belonging to hexosaminidase defect . It is named after the British ophthalmologist Warren Tay (* 1843, † May 15, 1927) and the American neurologist Bernard Sachs (* January 2, 1858, † February 8, 1944), who first developed the disease in 1881 and 1881, respectively Documented in 1898. The disease leads to a progressive reduction in cognitive abilities, psychomotor degradation , muscular hypotension , paralysis , spasticity , blindness and deafness, epileptic seizures, to a cherry-red spot in the macula and death within a few years.
Epidemiology
The frequency of the mutation responsible for the disease ( chromosome 15 , locus 15q23-24, also called the alpha chain ) is noticeably increased in Ashkenazi Jews of Eastern European origin. It is also particularly common among French Canadians , Irish and Cajuns . There, the frequency of heterozygous carriers is estimated at 1:25.
etiology
GM 2 - gangliosides are usually continuously degraded by sequential cleavage of the terminal sugar. The affected children lack the enzyme β-N-acetylhexosaminidase, which is responsible for removing terminal N-acetylgalactosamine residues. As a result, the ganglioside levels in the child's brain and retina are dramatically increased. After the affected nerve cells are inflated, they ultimately die.
diagnosis
The disease is mostly recognized between the third and eighth month of life. Evidence is given due to the reduced activity of hexosaminidase A or B in blood serum , leukocyte or fibroblast cultures. Detection of heterozygotes is also possible ( prenatal diagnosis ). In Tay-Sachs disease, the ganglioside GM2, which is an important component of the plasma membrane of nerve cells in the central nervous system (CNS), cannot be broken down due to a lack of hexosaminidase A. The accumulation leads to cell death and demyelination , which are manifested by muscle weakness and loss of vision as a result of optic atrophy .
Symptoms
- Cherry-red spot on the macula in over 95% of patients
- Increasing muscle weakness after the third month of life
- Fright reactions to sound stimuli
- Psychomotor degradation, loss of the ability to sit and stand
- Increasing hearing loss, blindness, paresis and spasms
- Doll-like face with pale translucent skin, long eyelashes, fine hair and a striking pink complexion
In addition to this:
- In the late infancy, increasing vomiting and recurrent pneumonia
- After the age of 16 months, progressive macrocephaly due to cerebral gliosis . In addition, the lipidosis of cortical , autonomic and rectal mucosal neurons with ballooned cytoplasm and peripherally displaced cell nucleus occurs. Progressive demyelination as well as cortical gliosis are another characteristic. No pathological changes in visceral organs can be observed here.
forecast
Patients usually die by the age of three due to recurrent pneumonia .
therapy
Only the symptoms can be treated.
Prevention
In particularly affected population groups, appropriate observation programs are carried out to record heterozygous carriers, for example by the organization Dor Yeshorim . These can serve to determine the parent's ownership as well as the risk of occurrence in the next generation.
To avoid the disease, pregnancy is not recommended if both parents are known to be carriers. Families in which the disease has already occurred use the possibility of genetic counseling prior to pregnancy or prenatal diagnostics (PND). The chorionic villus sampling can be used to obtain biopsy material from the tenth week of gestation, also the amniocentesis .
In the course of in vitro fertilization (IVF), preimplantation diagnostics (PGD) can provide information about the risk, as with other genetic dispositions. Legal restrictions must be observed here, and the procedure is complex and therefore cost-intensive.
See also
Web links
- Tay-Sachs syndrome. In: Online Mendelian Inheritance in Man . (English)
- Tay-Sachs disease , lexicon of biology - spectrum of science
- Self-help group for the German-speaking area (hand in hand against Tay-Sachs and Sandhoff)
- Jan Osterkamp: New genetic tool: More precise tool for DNA rewriting , on: Spektrum.de from October 22, 2019
Individual evidence
- ^ Warren Tay: Symmetrical changes in the region of the yellow spot in each eye of an infant . In: Transactions of the Ophthalmological Society of the United Kingdom . tape 1 , 1881, ISSN 0078-5334 , p. 55-57 ( digitized version ).
- ^ Bernard Sachs: On arrested cerebral development, with special reference to its cortical pathology. In: The Journal of Nervous and Mental Disease . tape 14 , no. 9/10 , 1887, ISSN 0022-3018 , p. 541-553 ( digitized version ).
- ↑ Tay-Sachs Diseases (Eng.)
- ^ Josef Ekstein, Howard Katzenstein: The Dor Yeshorim story: community-based carrier screening for Tay-Sachs disease . In: Advances in Genetics . tape 44 , 2001, ISSN 0065-2660 , p. 297-310 , doi : 10.1016 / S0065-2660 (01) 44087-9 , PMID 11596991 .
- ^ Nomi Stone: Erasing Tay-Sachs Disease. (No longer available online.) Archived from the original on June 22, 2006 ; Retrieved August 16, 2006 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.
- ↑ Chorionic villus sampling and amniocentesis: Recommendations for Prenatal Counseling. United States, Center for Disease Control, accessed June 18, 2009 .
- ↑ Molina as Dayal: Preimplantation Genetic Diagnosis. eMedicine.com, December 30, 2015, accessed December 18, 2017 .
