hexosaminidase A deficiency

What is Hexosaminidase A Deficiency (Tay-Sachs Disease)?

Hexosaminidase A deficiency (HEX A deficiency), also known as Tay-Sachs disease, is caused by harmful genetic changes in the HEXA gene. It is a condition that mainly affects the nervous system. Individuals with Tay-Sachs disease do not have enough functional beta-hexosaminidase A enzyme. The beta-hexosaminidase A enzyme normally breaks down a substance called GM2 ganglioside. Without enough functional beta-hexosaminidase A enzyme, GM2 ganglioside builds up in the brain and other nerve cells and causes them to die.

Because of the ongoing damage to the brain and nerve cells, individuals with Tay-Sachs disease experience neurological symptoms that become more severe over time. There are several forms of Tay-Sachs disease, including acute infantile (classic), subacute juvenile, and late-onset forms.

Acute Infantile (Classic) Form

Classic Tay-Sachs disease is the most common and severe form. It is a progressive condition that results in the gradual loss of movement and mental function. It is typically fatal early in childhood.

The symptoms of classic Tay-Sachs disease usually appear in infants between three and six months of age. Parents or caregivers may notice that they appear to be paying less attention with their eyes (decreased visual attentiveness) and are easily startled, and they will begin to lose the ability to turn over, sit, or crawl. As the disease progresses, infants with classic Tay-Sachs disease develop seizures, vision loss, an enlarged head size, and eventually become paralyzed. Death typically occurs by the age of four.

Subacute Juvenile Form

Individuals with subacute juvenile Tay-Sachs disease typically begin to show symptoms between the ages of two and ten. Early signs can include weakness, clumsiness, and difficulties with speech. As the disease progresses, individuals experience a loss of their speech, motor, and cognitive skills. Other symptoms include stiff (spastic) movements, seizures, and difficulty swallowing. Death often occurs in the teenage years. There can be variability in the age of onset and symptoms experienced even among individuals from the same family.

Late-Onset Form

The symptoms of late-onset Tay-Sachs disease are typically recognized in an individual's twenties or thirties, though some may have subtle features as early as childhood. Individuals may experience muscle weakness, involuntary muscle twitching, speech difficulties, altered thought processes, or severe mental disorders like psychosis or schizophrenia. Symptoms tend to progress more slowly than in other forms of Tay-Sachs disease. There is considerable variability in the age of onset and types of symptoms individuals experience with this form of the disorder, even within a single family. Symptoms of late-onset Tay-Sachs disease can appear similar to other more common diseases, which can sometimes lead to a misdiagnosis.

How common is Tay-Sachs disease?

The incidence of classic Tay-Sachs disease in the population is 1 in 320,000 births. It is more common among individuals of Ashkenazi Jewish, French-Canadian, Louisiana Cajun, and Pennsylvania Amish descent. The incidence of other forms of Tay-Sachs disease is unknown.

How is Tay-Sachs Disease treated?

At this time there is no cure for Tay-Sachs disease, and treatment largely focuses on ensuring proper nutrition and hydration, protecting the ability to breathe, managing any infections, and controlling seizures with medication.

There is also no cure for the juvenile and late-onset forms of Tay-Sachs disease. Treatment largely addresses symptoms as they arise, such as assisting mobility with mechanical aids or controlling seizures and mental disorders with medication. Because the symptoms of these forms of the disease vary widely, treatment depends on the types of symptoms and their severity.

What is the prognosis for an individual with Tay-Sachs Disease?

Even with treatment, children affected by classic Tay-Sachs disease usually die by the age of four.

The prognosis for an individual with the other forms of Tay-Sachs disease can vary, depending on both the age of onset and the severity of symptoms. Those with juvenile-onset Tay-Sachs disease typically experience progressive loss of skills between the ages of two and ten and death occurs in the teenage years. In more severe cases, those with juvenile-onset Tay-Sachs disease can die in early childhood.

The prognosis for those with the late-onset form varies even more. The lifespans of individuals with late-onset Tay-Sachs disease are not well studied and can be difficult to predict, though there are certainly examples of people with this condition who live into their sixties or seventies.