Tay-Sachs disease
Tay-Sachs disease is a hereditary neurodegenerative disorder resulting from excess storage of GM2 ganglioside within the lysosomes of cells.
Epidemiology
The incidence of the disease is estimated to be 1 in 3,600 in Ashkenazi Jews with a carrier frequency of 1 in 30 and 1 in 360,000 in other populations with a carrier frequency of 1 in 300. Tay-Sachs disease is the most frequently occurring sphingolipidosis.
Pathology
Tay-Sachs disease is a lysosomal storage disease, which together with Sandhoff syndrome and AB variant comprise the GM2 gangliosidoses.
Tay-Sachs disease is due to a mutation of the HEXA gene that results in reduced levels of the enzyme hexosaminidase-A (hex-A) which in turn results in the accumulation of GM2-ganglioside within the cells of the nervous system .
Clinical presentation
At 3 to 6 months
- decreased eye contact
- twitchy eyes (myoclonic jerks)
- difficulty focusing on objects
- excessive startling by sharp but not necessarily loud noises
At 6 to 10 months
- limp and floppy muscles (hypotonia)
- decreased alertness and playfulness
- difficulty sitting up or rolling over
- loss of motor skills
- decreased hearing and eventual deafness
- gradual loss of vision
- an abnormal increase in head size (macrocephaly)
10 months and older
As a child with Tay-Sachs grows older, he or she may become blind, intellectual impaired, paralyzed, and unresponsive to the environment. The child also may have seizures, difficulty swallowing, and difficulty breathing. Children with Tay-Sachs disease rarely live beyond 4 or 5 years of age .
Screening
Screening for Tay-Sachs disease is recommended for people in high-risk groups. This includes people of Ashkenazi Jewish descent and anyone with a history of the condition in their family.
- preconception screening: where potential parents are able to check whether they carry the HEXA mutation before starting a family
- antenatal screening: where a fetus is checked to see whether two copies of the HEXA mutation have been inherited, which would cause Tay-Sachs disease to develop
Radiographic features
CT
Macrocephaly and reduced attenuation of the cerebral white matter have been reported on CT scans in patients with GM2 gangliosidosis .
MRI
MRI is superior to CT in delineating deep white matter demyelination. Thalami may show changes consistent with calcification, best seen on T2* weighted sequences. No abnormal contrast enhancement is described .
Treatment and prognosis
No specific treatment is currently available for Tay-Sachs disease. Management is therefore supportive.
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