Tay-Sachs Disease

Tay-Sachs disease is a terminal genetic disorder in which harmful quantities of a fatty substance called ganglioside GM2 accumulate in the nerve cells in the brain. Infants with Tay-Sachs disease appear to develop normally for the first few months of life. Then, as nerve cells become distended with fatty material, a relentless deterioration of mental and physical abilities occurs. The child becomes blind, deaf, and unable to swallow. Muscles begin to atrophy and paralysis sets in.
A much rarer form of the disorder that occurs in patients in their twenties and early thirties is characterized by unsteadiness of gait and progressive neurological deterioration.
Patients with Tay-Sachs have a "cherry-red" spot in the back of their eyes. The condition is caused by insufficient activity of an enzyme called hexosaminidase A that catalyzes the biodegradation of acidic fatty materials known as gangliosides. Gangliosides are made and biodegraded rapidly in early life as the brain develops. Patients and carriers of Tay-Sachs disease can be identified by a simple blood test that measures hexosaminidase A activity. Both parents must be carriers in order to have an affected child (which makes it a recessive trait on the 15th chromosome). When both parents are found to carry a genetic mutation in hexosaminidase A, there is a theoretical 25 percent chance with each pregnancy that the child will be affected with Tay-Sachs disease. Prenatal monitoring of pregnancies is available.
Presently there is no treatment for Tay-Sachs. Even with the best of care, children with Tay-Sachs disease usually die by age 5.
Notably, this is a familial disorder found in east European Jewish (Ashkenazi) families. Symptoms begin to appear at 3 to 6 months old and progress rapidly, and the child usually dies before 3 years old. The only known risk factor is familial descent. In this group, the rate of fatality/birth with the disorder is 1 out of 2,500 people.
Symptoms include:

• Blindness
• Deafness
• Dementia
• Listlessness
• Irritability
• Seizures
• Paralysis
• Decreased muscle tone (loss of muscle strength)
• Muscle function loss
• Temper or agitation (exaggerated startle response)
• Delayed mental and social skills
• Growth (slow)

source: National Ty-Sachs & Allied Diseases Association, Inc.

Thaks to LadySun for bugging me to make this writeup more accurate. Creds go to her for the Chromosome 15 clarification.

Tay-Sachs disease is found predominately among Ashkenazi Jews (as mentioned above), and among French Canadians. About 1 in 30 Ashkenazi Jews, and 1 in 40 French Canadians is a carrier. Being a carrier means having a mutated HexA gene.

These two separate groups had interbred a lot in the past (and still do), and this accounts for the fact that Tay-Sachs is found almost exclusively in these two populations. But how come it's found in two populations that are so far apart from each other? Ashkenazi Jews come from Eastern Europe, and French Canadians come from Canada (the disease is not found in France). Isn't it strange that the same disease is found in two very separate populations?

This problem bothered biologists for a long time, and particularly studiers of evolution. How could exactly the same mutation have happened on two separate occasions? This is simply statistically impossible. This is about as likely as a troupe of alligators prancing into your bedroom right now and performing a tear-jerking rendition of 'Casablanca'. But as it turns out, it makes sense after all.

The answer is that the phenotype of the disease is the same in both cases: there is no production of the Hexosaminidase A enzyme. The lack of this enzyme causes all the symptoms explained in dko's w/u. But the genotype is different. The HexA gene in Ashkenazis and in French Europeans is ruined by different mutations. So in both cases, there is some problem with the gene that causes it to stop producing Hexosaminidase A, but the mutation is different.