Disease

TAY-SACHS DISEASE

It is an extremely rare genetic disorder in which the enzyme that breaks down fatty acids in the body is absent.

Frequency

Its variants are frequently found in Eastern and Central European Jewish communities; also common in Quebec French-Canadian communities, Louisiana Cajun population and Pennsylvania Old Order Amish community.

Inheritance

Tay-Sachs disease is inherited in an autosomal recessive pattern.

History of Disease

The first recorded case was observed by the British ophthalmologist Warren Tay in 1881 when he observed the retina of a one-year-old patient which has a cherry-red spot and exhibited physical and mental retardation, clearly a sign of degenerative function of the central nervous system. The disease was named after Warren Tay, for his observation about the cherry-red spot on the retina of the eye, and American neurologist Bernard Sachs for his observation in the cellular changes in patients diagnosed with the disease and increased rate of disease in Ashkenazi Jews.

Brief Summary

History of Disease

Brief Summary

Source

Image:

Child with Tay-Sachs

Pathogenesis

Tay-Sachs disease is caused by mutations in the HEXA gene that is located on chromosome 15 at position 24.1. Hexa gene provides instructions for producing beta-hexosaminidase A, an enzyme that plays a critical role in the brain and spinal cord. It helps break down a GM2 ganglioside, a fatty substance or lipid that is essential for normal metabolism and accumulation of this is highly toxic and may cause cell death. The functionality of the beta-hexosaminidase A is known to be disrupted by the mutations in the HEXA gene, which prevents the enzyme from breaking down GM2 ganglioside. Accumulation of this enzyme causes high significant levels of toxicity in neurons in the brain and spinal cord. As a result, the build up of the GM2 ganglioside causes destruction of the neurons that causes the signs and symptoms seen in Tay-Sachs disease.

Source

Image:

Location of the HEXA gene on chromosome 15

Source

Image:

A type of mutation that led to the disorder

Symptoms

Infantile Tay-Sachs Disease

Progressive muscle weakness
Myoclonic jerks
Jaundice
Exaggerated startle response
Loss of motor skills
Decreased eye function
Shows listlessness and irritability
Slow growth
Diminished muscle tone
Involuntary muscle spasms
Development of cherry red spots in the eyes.
Seizures
Progressive hearing loss
Dementia

Juvenile (Subacute) Tay-Sachs Disease

Loss control of body movements (ataxia)
Mental retardation
Jaundice
Progressive loss of speech
May or may not develop a cherry-red spot in the eyes.
Degeneration of the nerve that carries impulses from the eye to the brain to form images
May have retinitis pigmentosa

Late-Onset Tay-Sachs Disease

Mood alterations
Jaundice
Progressive muscle weakness
Fasciculations
Seizures
slurred speech (dysarthria)
Inability to coordinate voluntary movements (ataxia)
Dystonia
Involuntary muscle spasms
Mental deterioration
Experience of psychiatric episodes such as loss of contact with reality, paranoia, hallucinations, bipolar episodes, and depression

Tay-Sachs disease is a progressive neurodegenerative disorder which, in the classic infantile form, is usually fatal by age 2 or 3 years.

Social Concerns

Genetic testing helps determine a person’s chance of developing or passing on a genetic disorder. Concerns surrounding the disease are as follows:

Psychological

Unnecessary anxiety created

Social

Expense swell health costs
Societal pressure not to bear affected offspring

Treatment

No specific treatment for Tay Sachs disease is available. Treatment is only directed toward the specific symptoms that are apparent in each individual such as:

anticonvulsants that may be used to treat seizures
nutritional support and supplementation for infants who have feeding difficulties
physical therapy to help keep joints flexible and maintain mobility
respiratory care such as chest physiotherapy (CPT) for patients who have difficulty of breathing

Source

Image:

Chest physiotherapy performed on affected baby

Clinical Trials

Title:

Effects of Miglustat Therapy on Infantile Type of Sandhoff and Taysachs Diseases (EMTISTD) (EMTISTD)

Intervention:

Drug: Miglustat

Phase:

Phase 3

Procedure:

Treatment with Zavesca regimen based on body surface area as follows: SQRT [Height (cm) × Weight (kg)] / 3600 <1.25 : 200mg TDS 0.88- 1.25: 200mg BID 0.73- 0.88: 100 mg TDS 0.47- 0.73: 100 mg BID <0.47: 100 mg Daily

Other Name:

Zavesca

Goal:

Recent studies have suggested new methods of treatment, such as enzyme replacement therapy, bone marrow transplantation and substrate reduction therapy (SRT). The first drug used in SRT was Miglustat. It was introduced in 1980 as an anti HIV agent and later, it was registered under the trademark of Zavesca in 2009 and was used in treatment of Gaucher and Niemann-Pick disease. Zavesca passes the blood brain barrier, so causes reduction of cholesterol and glycosphingolipids CNS neurons and relief of neurologic manifestations. Improvements were seen in oculomotor function, cognition, swallowing, motor disturbances and psychological problems after treatment with Zavesca. No effect has been proved on visceral involvement. Weight loss during the first year of treatment, diarrhea and dyspepsia are seen as side effects. So this study is done to evaluate the effect of Miglustat therapy in Sandhoff and Tay sachs disease, and is believed to help for further studies in this field.

Further details at:

https://clinicaltrials.gov/ct2/show/NCT03822013?cond=tay+sach+disease&draw=2&rank=10

Clinical Trials

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