hexosaminidase A deficiency

What Is Hexosaminidase A Deficiency?

Hexosaminidase A Deficiency (HEX A deficiency), caused by mutations in the HEXA gene, is an inherited disease that causes brain and other nerve cells to die. Mutations in the HEXA gene cause a deficiency of the beta-hexosaminidase A enzyme which can lead to severe neurological and mental problems. This enzyme helps break down a particular fatty acid called GM2 ganglioside. Without adequate amounts of functional enzyme, GM2 ganglioside will build up in nerve cells and cause them to die.

There are several forms of HEX A deficiency, including acute infantile (Tay-Sachs disease), juvenile, chronic, and adult-onset forms.

Acute Infantile Form (Tay-Sachs Disease)

Tay-Sachs disease is the most common and severe form of HEX A deficiency. Tay-Sachs disease 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 Tay-Sachs disease usually appear in infants between three and six months of age. Initially, infants lose the ability to turn over, sit, or crawl. They also become less attentive and develop an exaggerated startle response to loud noise. As the disease progresses and nerve cells further degenerate, infants with Tay-Sachs develop seizures, vision and hearing loss, mental disabilities, and eventually become paralyzed. Death usually occurs by the age of four.

Juvenile-Onset Form

Those with juvenile-onset HEX A deficiency typically begin to show symptoms between the ages of 2 and 10. Early signs can include a decline in verbal skills, the ability to accomplish life skills, and overall thought processes. These symptoms become progressively worse over time. The child will also develop spastic movement, seizures, and vision loss. Most children with the juvenile-onset form of HEX A deficiency will enter a vegetative state by the age of 10 to 15.

Chronic Form

Symptoms of the chronic form of the disease can begin any time from early childhood until the age of 10. While this form of HEX A deficiency can cause a variety of movement problems, the decline of verbal skills and thought processes tend to occur later than in the juvenile form.

Adult-Onset Form

Adult-onset HEX A deficiency is rare, but it is thought that symptoms begin in one's twenties or thirties. This form of the disease has the greatest variation in symptoms from person to person, even among individuals in the same family. Often its symptoms appear identical to other more common diseases, leading to misdiagnoses. These symptoms can include some or all of the following: muscle weakness, involuntary muscle twitching, speech difficulties, altered thought, or severe mental disorders like psychosis or schizophrenia. Some individuals with adult-onset HEX A deficiency may develop movement disorders but be spared mental decline until their sixties or seventies. For some, adult-onset HEX A deficiency is not fatal.

How Common Is Hexosaminidase A Deficiency?

Tay-Sachs disease is most common among Ashkenazi Jews from Central and Eastern Europe, certain French-Canadian communities in Quebec, Amish populations in Pennsylvania, and Louisiana Cajuns. Tay-Sachs disease is found in individuals of all ethnicities, though the incidence outside of the ethnic groups mentioned above is much lower.

The incidence of Tay-Sachs disease in Ashkenazi Jewish individuals is approximately 1 in 3,600, compared to 1 in 360,000 for the non-Jewish Caucasian population. Since 1970, an organized campaign in the Jewish community to educate potential parents about Tay-Sachs and test them for mutations causing this disease has dramatically lowered the number of children affected by the condition. Because of these successful screening programs, today the majority of children born in the U.S. with Tay-Sachs disease do not have an Ashkenazi Jewish background.

The incidence of other forms of HEX A deficiency is unknown.

How Is Hexosaminidase A Deficiency Treated?

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

There is also no cure for these later-onset forms of HEX A deficiency. Treatment largely addresses symptoms as they arise, such as aiding 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 Hexosaminidase A Deficiency?

Even with the best care available, children affected by Tay-Sachs disease usually die by the age of four. They have worsening seizures and lapse into an unresponsive vegetative state.

The prognosis for an individual with the other forms of HEX A deficiency can vary widely, depending both the age of onset and the severity of symptoms. Those with juvenile-onset or chronic HEX A deficiency typically experience severe mental decline between the ages of 2 and 10 and often reach a vegetative state between the ages of 10 to 15, with death following several years later. In more severe cases, those with juvenile-onset HEX A deficiency can die in early childhood. Those with the adult-onset form of the disease face more varied outcomes. Some may develop severe mental problems such as psychosis by age 20, while others may reach their sixties or seventies with movement difficulty but without mental problems. The lifespans of individuals with adult-onset HEX A deficiency are not well studied and can be difficult to predict. In some cases, the disease has not impacted lifespan.