Tay-Sachs Disease Case Study

On April 21st, the University of San Diego will host a public screening of the film “The Perfect 46”. The movie is set in the near future when genome sequencing is routine and widespread. The Perfect 46 is a 23andMe-like company that offers a genetic analysis service which compares the genomes of couples to identify whether or not they should have children together based on their personal risk of passing on a heritable disease. The goal of the company is to eradicate diseases like cystic fibrosis and sickle cell anemia by breeding them out of the population. The film is sometimes described as “science factual”, but its hypothetical genome screening service is not that different from some already existing technology. Before the FDA forced 23andMe to cease sales in the U.S., the company offered a “Family Traits Inheritance Calculator”. Couples that were both 23andMe customers could find out the probability of their children inheriting traits like bitter taste perception or lactose tolerance. The plausibility of the movie premise makes discussions about the ethics involved even more pressing.

In one of the most compelling scenes of the movie, the protagonist, Jesse Darden, defends the mission of The Perfect 46 at a panel debate. At first he shies away from using the word “eugenics” to describe their goal of eradicating heritable disease, aware of the baggage it carries. But later in the discussion he points to the true definition of eugenics, which involves using genetics to improve the human race, and embraces it. Jesse posits, “…. maybe eugenics doesn’t have to be a dirty word”.

The Ashkenazi Jewish population’s attempt to eliminate Tay-Sachs disease from their gene pool is a compelling example of using genetic information to influence reproductive decisions. Ashkenazi Jewish individuals trace their ancestry to Eastern Europe and make up the majority of people that identify as Jewish in the United States. Children with Tay-Sachs disease are born healthy but begin to deteriorate within 3-6 months of birth. Loss of neural function leads to hearing/vision loss, paralysis, and death within the first few years of life. Beginning in the 1970s, a population-based carrier screening program was launched, drawing on the coordinated efforts of community organizers, medical professionals, and religious leaders. One in 27 Ashkenazi Jews is a carrier of Tay-Sachs, and if two carriers of this recessive gene marry, their children will have a 25% chance of inheriting Tay-Sachs. The success of the screening program is indisputable; cases of Tay-Sachs in the U.S. and Canada have dropped by 90 percent.

According to the Oxford Dictionary, eugenics is:

"The science of improving a human population by controlled breeding to increase the occurrence of desirable heritable characteristics" Not having Tay-Sachs is certainly a desirable characteristic. And, the fact that the number of Tay-Sachs cases in the U.S. has dropped so dramatically suggests that the “breeding” of carriers has been impacted by the screening program in some capacity. Therefore, the Tay-Sachs screening program can be considered eugenic based on the provided definition.

Are we ready to accept that genetics and genetic technology can improve the human race? Or are the dark history of eugenics and the possibility of misuse moving forward too heavy a burden for this field of study to proceed?

Please take our poll below and leave a comment. If you will be in the San Diego area on April 21st and wish to attend the movie screening, you may make a free reservation here.


Genome News Network. The Success Story of Gene Tests (2001).

Image Credit: Brett Ryan Bonowicz

Case details

A boy was born normal but started flinching at loud noises (enhanced startle response) at the age of 6 months. The child initially could sit up, but then regressed so that he could not roll over or recognize his parents.

Ophthalmological examination revealed a central red area of the retina surrounded by white tissue (Cherry red spot).

What is the treatment for this disease?

Case Discussion

The child is suffering from Tay Sach’s disease (GM2 Gangliosidosis). The disease is named after the British ophthalmologist Warren Tay who first described the red spot on the retina of the eye, and the American neurologist Bernard Sachs who described the cellular changes of Tay-Sachs and noted an increased prevalence in the Eastern European Jewish (Ashkenazi) population

Basic Concept

Gangliosides have been isolated from the ganglion cells, neuronal bodies, dendrites, spleen and RBC stroma. The highest concentration is found in the grey matter of brain. Structurally they contain a long chain fatty acid, alcohol sphingosine, a carbohydrate moiety which is usually glucose/ and or galactose, and at least one molecule of N-acetyl –Neuraminic acid (NANA)(Figure-1). Four important types of Gangliosides are GM-1, GM-2, GM-3 and GD-3.GM-1 is more complex ganglioside and is known to be the receptor for cholera toxin in human intestine. Gangliosides are mainly components of membranes. They also serve as receptors for circulating hormones and thereby influence various biochemical processes in the cells.

Case details

The GM2 Gangliosidosis  also called Tay-Sach’s disease results from the deficiency of ß-hexosaminidase activity and the lysosomal accumulation of GM2 gangliosides, particularly in the central nervous system, causing severe effects (neurodegeneration).The child in the given case was born normal but developed progressive deterioration of the neurological functions. This is characteristic of this disease

Tay-Sachs disease

Biochemical defect

There is deficiency of ß hexosaminidase A enzyme. This Lysosomal enzyme removes amino hexose groups from Gangliosides, Subsequently the other components are hydrolyzed by other specific enzymes. In its deficiency the gangliosides are  not degraded  thus accumulate in various tissues especially nervous tissue.

[ß-Hexosaminidase occurs as two isozymes: ß-hexosaminidase A, which is composed of one a and one ß subunit, and ß-hexosaminidase B, which has two ß subunits. ß-hexosaminidase deficiencyA results from mutations in the a subunit and causes Tay-Sachs disease, whereas mutations in the ß-subunit gene result in the deficiency of both ß-hexosaminidase A and B and cause Sandhoff disease.]

Figure-2- Cherry red spot on the macula


It is inherited as an autosomal recessive traits, with a predilection in the Ashkenazi Jewish population, where the carrier frequency is about 1/25.

Clinical symptoms and Classification

Tay-Sachs disease is classified in variant forms, based on the time of onset of neurological symptoms.

Infantile TSD patients with this disease are born normal, but they develop loss of motor skills, increased startle reaction, macular pallor and retinal cherry red spot(Figure-2).Affected children develop normally till the age of 5-6 months, then decreased eye contact, hyperacusis (Exaggerated startle response) to noise are noted. Progressive development of idiocy and blindness are diagnostic of this disease and they are due to wide-spread injury to ganglion cells, in brain and retina. The cherry red spot about the macula is due to destruction of retinal ganglion cells exposing the underlying vasculature(Figure-2). Macrocephaly not associated with hydrocephalus may be there. Convulsions are seen in severe cases.

Juvenile TSD. Extremely rare, Juvenile Tay-Sachs disease usually presents itself in children between 2 and 10 years of age. They develop cognitive, motor, speech difficulties (dysarthria), swallowing difficulties (dysphagia), unsteadiness of gait (ataxia), and spasticity. Patients with Juvenile TSD usually die between 5–15 years.

Adult/Late Onset TSD. A rare form of the disorder, known as Adult Onset Tay-Sachs disease or Late Onset Tay-Sachs disease (LOTS), occurs in patients in their 20s and early 30s. It is characterized by unsteadiness of gait and progressive neurological deterioration. Symptoms of LOTS, which present in adolescence or early adulthood, include speech and swallowing difficulties, unsteadiness of gait, spasticity, cognitive decline, and psychiatric illness, particularly schizophrenic-like psychosis.


The diagnosis of infantile Tay-Sachs disease is usually suspected in an infant with neurologic features and a cherry-red spot.

Enzymatic Assays-Definitive diagnosis is by determination of the level of ß-hexosaminidase A in isolated blood leukocytes.

Fine needle Aspiration Cytology of brain tissue – can show the degree of neuronal degeneration. FNAC has a great potential for diagnosis and follow-up of Tay-Sachs disease

Prenatal screening-Future at-risk pregnancies for both disorders can be monitored by prenatal diagnosis by amniocentesis or chorionic villus sampling.

Carrier screening– Identification of carriers within families is also possible by ß-hexosaminidase A and B determination. Indeed, for Tay-Sachs disease, carrier screening of all couples in whom at least one member is of Ashkenazi Jewish descent is recommended before the initiation of pregnancy to identify couples at risk. These studies can be conducted by the determination of the level of ß-hexosaminidase A activity in peripheral leukocytes or plasma.


No cure for this disease. Symptomatic treatment is given. Enzyme replacement therapy and Gene therapy are under trial. Although experimental work is underway, no current medical treatment exists for infantile TSD. Patients receive palliative care to ease the symptoms. Infants are given feeding tubes when they can no longer swallow. Improvements in palliative care have somewhat lengthened the survival of children with TSD, but no current therapy is able to reverse or delay the progress of the disease.


Prognosis is bad and death occurs in early years of life.


Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

One thought on “Tay-Sachs Disease Case Study

Leave a Reply

Your email address will not be published. Required fields are marked *