Tay–Sachs disease
The Tay- Sachs disease, also known under the names disease Tay -Sachs and infantile amaurotic idiocy ( congenital severe mental retardation with blindness ), is an autosomal recessive disorder, with disease Sandhoff belonging to the GM2 - gangliosidosis with Hexosaminidasedefekt lipid metabolism disorder. 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 ) named, which for the first time or the disease in 1881. documented in 1898. The disease leads to progressive reduction of cognitive abilities, psychomotor degradation, muscular hypotonia, paralysis, spasticity, blindness and deafness, seizures, the cherry-red spot in the macula and within a few years to death.
Epidemiology
( Called chromosome 15, locus 15q23 -24, and alpha chain) The frequency of the mutation responsible for the disease is increased strikingly among Ashkenazi Jews of Eastern European origin. Also is particularly common in French Canadians, Irish and Cajuns. There, the frequency of heterozygous carriers is estimated to be 1:25.
The occurrence of the disease is kept low by genetic studies in advance of pregnancies and where adequate findings with the aim of avoid them.
Etiology
GM2 gangliosides are normally continuously degraded by sequential cleavage of the terminal sugar. The affected children lack the enzyme β -N- acetylhexosaminidase, which is responsible for the removal of the terminal N - Acetylgalactosaminresten. Therefore, the ganglioside is dramatically increased in the brain and retina of the child. Finally, after inflation of the affected nerve cells leads to their downfall.
Diagnosis
The disease is usually detected between the third and eighth month of life. The proof is given due to reduced activity of hexosaminidase A and B in blood serum, leukocytes or fibroblasts cultures. A Heterozygotennachweis is possible ( prenatal diagnosis ). In Crohn's Tay -Sachs ganglioside GM2 can, which is an important component of the plasma membrane of nerve cells in the CNS, due to a deficiency of hexosaminidase A can not be eliminated. The accumulation leads to cell death and demyelination, which are manifested by muscle weakness and loss of vision due to optic atrophy.
Symptoms
- Cherry red spot on the macula over 95 % of patients
- Increasing muscle weakness after the third month of life
- Startle responses to sound stimuli
- Psychomotor degradation, loss of sitting and standing ability
- Increasing deafness, blindness, paralysis and spasms
- Doll -like face with pale translucent skin, long eyelashes, fine hair and striking pink complexion
In addition to this:
- In the late infancy increasing vomiting, and recurrent pneumonia
- After the 16th month of life progressive macrocephaly due to cerebral gliosis. In addition, the lipidosis occurs cortical, autonomic and rectal Mukosaneuronen with balloniertem cytoplasm and peripherally abgedrängtem nucleus. Progressive demyelination and cortical gliosis are another feature. Here, no pathological changes in visceral organs can be observed.
Forecast
The patients die usually up to the age of three because of recurrent pneumonia.
Therapy
It can only the symptoms are treated.
In particularly affected populations appropriate monitoring programs are carried out for the detection of heterozygous carriers. Families in which the disease has already occurred, use the possibility of genetic counseling prior to pregnancy or prenatal diagnosis. To prevent the disease, it is not recommended in pregnancy.
Weblink
Tay- Sachs disease at Online Mendelian Inheritance in Man