hexosaminidase A deficiency

What is Hexosaminidase A Deficiency?

Hexosaminidase A deficiency is an enzyme deficiency that causes brain and other nerve cells to die, which can lead to severe neurological and mental problems.

Hexosaminidase A (HEX A) deficiency is caused by a deficiency in an enzyme called beta-hexosaminidase A. This enzyme helps break down a particular fatty acid called GM2 ganglioside. Without adequate amounts of functional enzymes, 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, or adult-onset forms.

Acute infantile (Tay-Sachs disease) - Tay-Sachs disease is the most common and severe form of hexosaminidase 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 - 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 HEX A deficiency will enter a vegetative state by the age of 10 to 15.

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

Adult-onset - Adult-onset HEX A deficiency is rare, but it is thought that symptoms often begin in one's 20s or 30s. This form of the disease has the greatest variation in symptoms from person to person, even among people 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 people with adult-onset HEX A deficiency may develop movement disorders but be spared mental decline until their 60s or 70s. For some, adult-onset HEX A deficiency is not fatal.

How common is Hexosaminidase A Deficiency?

Acute infantile (Tay-Sachs disease) - Tay-Sachs disease is most common among specific ethnic populations, particularly 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 people of all ethnicities, though the risk outside of the ethnic groups mentioned above is much lower.

Roughly 1 in 30 Ashkenazi Jews is a carrier of Tay-Sachs, compared to 1 in 300 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 disease. 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.

Juvenile/Chronic/Adult-onset - The other forms of HEX A deficiency are extremely rare. Their exact prevalence is unknown. Mutations that cause these later-onset forms have been found in multiple ethnic groups.

How is Hexosaminidase A Deficiency treated?

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

Juvenile/Chronic/Adult-onset - There is also no cure for these later onset forms of hexosaminidase 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 is dependent upon the type of symptoms and their severity.

What is the prognosis for a person with Hexosaminidase A Deficiency?

Acute infantile (Tay-Sachs disease) - 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.

Juvenile/Chronic/Adult-onset - The prognosis for a person with these forms of hexosaminidase deficiency A can vary widely, depending on when in life the symptoms begin and the severity of the individual's case.

Those with juvenile 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, someone with juvenile 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 60s or 70s with movement difficulty, but without mental problems. The lifespan of people with adult-onset HEX A deficiency are not well understood and can be difficult to predict. In some cases, the disease has not impacted lifespan.