Tay-Sachs Disease


Also known as GM2 gangliosidosis or Hexosaminidase A deficiency.

An autosomal recessive genetic disorder.

Most common variant, known as infantile Tay–Sachs disease, it causes deterioration of mental and physical abilities that starts around six months of age and usually results in death by the age of four.

Asociated with ganglioside accumulation in the nerve cells of the brain, eventually leading to the premature death of those cells.

No cure or treatment for the disease.

Caused by a genetic mutation on the HEXA gene on chromosome 15.

The HEXA gene is located on the long (q) arm of chromosome 15 between positions 23 and 24.

Tay–Sachs disease is due to a frameshift mutation.

A large number of HEXA mutations have been discovered.

There are more than 100 mutations had been identified in the HEXA gene.
These mutations have included single base insertions and deletions, splice site mutations, missense mutations, and other more complex patterns. 
Each of these mutations alters the protein product, and thus inhibits the function of the enzyme.

Such mutations reach significant frequencies in French Canadians of southeastern Quebec, Ashkenazi Jews, and Cajuns of southern Louisiana.

Ashkenazi Jews: A four base pair insertion in exon 11 (1278insTATC) results in an altered reading frame for the HEXA gene. 
This mutation is the most prevalent mutation in the Ashkenazi Jewish population, and leads to the infantile form of Tay–Sachs disease.

Carrier rate in general population 1:300 and in Ashkenazi Jewish population the carrier rate as high as 1:30.

Cajun and French Canadian carrier rate is as high as the rate in Ashkenazi Jews.

Preconception and prenatal testing can identify carriers of Tay-Sachs disease by assaying hexosaminidase A and is recommended for screening if both members of a couple are Ashkenazi Jews, of French Canadian or Cajun descent.

Cajun: The same mutation found among Ashkenazi Jews occurs in the Cajun population of southern Louisiana.
Researchers have traced carriers from Louisiana families to a single founder couple, not known to be Jewish, that lived in France in the 18th century.

Classified in variant forms, based on the time of onset of neurological symptoms.

Heterozygous carriers, individuals who inherit one mutant allele, show abnormal enzyme activity, but have no symptoms of the disease. 
A heterozygous individual expresses at least 50% of the normal level of enzyme activity due to expression of the wild-type allele, and thid is usually sufficient to prevent phenotypic expression.

Infantile Tay–Sachs disease associated with normal development for the first six months, then nerve cells become distended with gangliosides leading to progressive deterioration of mental and physical abilities.

Infantile Tay–Sachs disease results in blindness, inability to swallow, and paralysis.

Signs and symptoms of Tay-Sachs disease can include the following:

  • Loss of motor skills, including turning over, crawling and sitting up
  • Exaggerated reactions when the baby hears loud noises
  • Seizures
  • Vision and hearing loss
  • “Cherry-red” spots in the eyes
  • Muscle weakness
  • Movement problems

Juvenile Tay–Sachs disease is extremely rare process that presents in children between two and 10 years of age.

Juvenile Tay–Sachs disease associated with cognitive and motor skill deterioration, dysarthria, dysphagia, ataxia, and spasticity and patients usually die between five and fifteen years.

Adult/Late Onset Tay–Sachs disease occurs in people in their 20s and early 30s, and is a rare non-fatal disease associated with impaired of gait and progressive neurological deterioration with spasticity, cognitive impairment, psychiatric ilnness, especially schizophrenic like illness.

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