Tay-Sachs disease: causes, diagnosis, treatment

Early childhood amaurotic idiocy or Tay-Sachs disease (Sachs idiocy, GM2 gangliosidosis) is a genetic pathology whose essence is a deficiency of the enzyme hexosaminidase A due to gene mutations. This, in turn, leads to cumulation of lipid molecules in neurons and causes impairment of brain and spinal cord function. What is the manifestation of such degradation, what special diagnostic methods exist, and what is the palliative therapy for such a condition, you will learn from the article.


  1. General information.
  2. Etiopathogenesis.
  3. Classification and symptoms.
  4. Complications.
  5. Diagnosis.
  6. Treatment of Tay-Sachs disease.
  7. Prognosis and prevention.

General Information

Disease is a type of lysosomal accumulation disease. The pathology owes its name to the writings of two doctors: the American neurologist . Sachs and the English ophthalmologist W. Tay. They were the first independent of each other to publish information about the pathology at the end of the last century. The disease is rare, according to statistics in the general population, the average frequency of carriers of the recessive altered gene is about 0.3%.

The syndrome has no gender coloring, but there are racial features: the highest rates of pathology are among Ashkenazi Jews who practice closely related marriages, as well as among Franco-Canadians and Cajuns. The age peak of the disease is under 2 years of age; symptoms in adolescents and adults are rare.


The main trigger for the pathology is mutations in the HEXA gene, which is located on the long arm of chromosome 15. It codes for enzymes that control metabolism. Tay-Sachs disease is inherited autosomal recessively, requiring two mutated genes to develop the disease. The risk exists only if both parents carry the mutation and is 25%. Thus, the disease can debut in any generation regardless of the timing of the mutation. Carriage is latent for a long time, in which case the dominant or healthy gene can guarantee enzyme production by 50%, which is quite sufficient for normal biochemical processes.

By the beginning of the new millennium, more than 100 gene mutations in the gene responsible for the development of the disease had been discovered: insertions or deletions of base pair fragments, splice-site and point mutations, as well as other variants of changes in the gene structure. Each of these mutations suppresses enzymatic activity, changing the structure of the gene.

The large number of types of gene mutations explains several forms of pathology. Similarly, altered genes in an allele provoke a complete blockade of ganglioside breakdown processes. Inheritance of dissimilar changes in genes is more often manifested by minimization of rapid enzyme activity rather than by its complete inertia.

The basis for the development of the pathology is a deficiency of lysosomal enzyme activity, which catalyzes the biodegradation of glycosfingolipid molecules, which include gangliosides, carbohydrates, mucopolysaccharides, complex lipids associated with fat cells and leptin. Gangliosides are essentially a type of fatty acids whose lipid components sprout into the membranes of neurons and glia cells.

They are affiliated with leptin and leptin resistance only because they are lipids. Moreover, these biocomponents guarantee neuron functioning by influencing the speed of nerve impulse movement, distribution of received information, and its storage. Normally, they are quickly broken down after performing their functional duties.

Only three components are needed for hydrolysis: the alpha- and beta-fragments of hexosaminidase A, the activator GM2A of protein nature. If the alpha form of the enzyme is insufficient, biodegradation is inhibited or completely blocked. Gangliosides cumulate in lysosomes of brain and spinal cord cells, leading to their death.

Classification and symptoms

Depending on the nature of the mutation, the disease is rapidly progressive or slowly progressive.

The debut of the pathology occurs in infancy, adolescents or adults, so three forms of the disease are distinguished:

  1. Acute infantile, occurring after birth and progressive with deterioration of the infant’s motor activity, development of blindness, deafness, and paralysis. Fatal outcome is within a couple of years.
  2. Late juvenile, rare, debuting in the first 10 years, with loss of acquired complex skills: speech, writing, walking. The average life expectancy is 15 years.
  3. Chronic adult, sporadic cases that begin at age 20-30, with impaired speech, chaotic motor activity, psychosis. Lethality by time is unknown.

The clinical picture is a mirror of the degeneration of the central nervous system. In the infantile variant of the disease, its debut signs appear by three months of age and lead to the loss of all normal skills. The child stops holding its head, turning over on its stomach, saying the name, smiling, and making visual contact with relatives. After six months, there is a loss of contact with the outside world, apathy develops, lack of mobility, sensitivity to loud sounds and light is absent, the baby does not recognize loved ones and has difficulty focusing on the toys that he/she loves.

Muscle hypotonia increases, the baby does not try to sit up or pick up a toy. By 8 months, reflexes to sound and light, tactility and smell become stronger. The child is not interested in everything that is going on around him or her. By one year of age, swallowing function is impaired, there is almost no hearing or vision, breathing difficulties arise, muscles atrophy, cramps and paralysis occur. In the second year of life, symptoms of muscle hypertonicity and paralysis appear.

The juvenile form is less noticeable. At first there is only emotional instability, slight discoordination in any movement. Clumsiness grows towards adolescence, ataxia appears, the gait becomes shaky, hyperkinesia develops, schooling becomes impossible. In parallel, speech is disturbed, its fluidity is lost, the pronunciation of words is almost indistinguishable. Later, epileptic seizures, dementia, and paralysis develop.

The chronic form has the most minimal symptoms: abrupt change of mood, angular movement, slurred pronunciation of individual words. Within a few years, the intellect is impaired: the ability to think abstractly, compare, forgetfulness and absent-mindedness prevail. Mental disorders are formed: inadequacy, aggression, depression, hallucinatory psychoses. If the course is prolonged, dementia is of an organic nature.


Among the most serious are epilepsy with fatal injuries that occur during a seizure. In young children, infections due to reduced immunity. The most common cause of death is pneumonia.


The examination is performed by several narrow specialists and begins with the collection of anamnesis. As a rule, cases of pathology in relatives are identified. Differential diagnosis is made with degenerative diseases of the CNS, epilepsy, and idiocy.

It is possible to confirm the diagnosis by performing the following diagnostic manipulations:

  1. Examination of the ocular fundus with detection of a red spot on the retina opposite the pupil – this is a cumulation of gangliosides in the ganglion cells.
  2. Blood biochemical testing for the content of the alpha form of hexosaminidase A. In the acute pediatric variety, the values are zero; the other varieties give residual enzyme activity. There is also a genetic diagnosis of the pathology.
  3. Microscopy of neurons: in biosamples look at the content of glycosides, characteristic: degenerative change in cell size, swelling, bloating, fine-grained lipoid inclusions.


Today there are no effective methods of treating the pathology. The help is symptomatic, the essence is to keep the patient alive. Palliative therapy involves feeding through a tube due to the inability of patients to swallow, the use of antibacterial and antiviral drugs, immunostimulants and immunomodulators to suppress the accompanying secondary infection. Therapy with antiepileptic drugs is ineffective.

The search for ways to correct Tay-Sachs disease is ongoing. There are three lines of research: enzyme replacement therapy, gene therapy, and substrate-reducing therapy. Enzyme replacement therapy is ineffective because of the large molecule of hexosaminidase, which lacks the ability to cross the blood-brain barrier and cell membranes. Gene therapy is developing a technique for delivering fresh gene material into cells using a viral vector and stem cell transplantation. But so far there have been no encouraging results.

The third direction is considered the most promising: substrate-reducing therapy using the enzyme sialidase, which can activate the breakdown of GM2 gangliosides. A synthesized drug that stimulates the expression of lysosomal sialidases intracellularly is on the way.

Prognosis and prevention

The outcome of the disease is disappointing, the relative favorability of the course can be said only in the late form with a slow development of symptoms. At the debut of the pathology in young children and adolescents the fatal outcome is inevitable. To reduce the number of pathological cases, screening testing for enzyme levels and its bioactivity is used.

The result makes it possible to see carriers of the mutation, to carry out their medical and genetic examination when planning pregnancy. If carriage of the mutation gene is found in both parents or there is a history of similar disease in close relatives, prenatal genetic screening is performed in the first trimester of gestation. If the risk is detected, the pregnancy is recommended to be terminated.

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