Definition:
Chronic Hexosaminidase A Deficiency is caused by the absence of a vital enzyme called hexosaminidase A (Hex-A).  Without Hex-A, a fatty substance or lipid called GM2 ganglioside accumulates abnormally in cells, especially in the nerve cells of the brain. Gangliosides need to be biodegraded rapidly in early life, as the brain develops. This ongoing accumulation causes progressive damage to the cells. It is similar to Tay-Sachs disease, but develops much later and at a slower pace.  People with the late-onset condition have a small residual amount of Hex-A rather than a complete absence of the enzyme.

Symptoms:
The age of onset of symptoms associated with Chronic Hexosaminidase A Deficiency  ranges from early childhood to 10 years of age. Symptoms of Chronic Hexosaminidase A Deficiency include progressive dystonia, spinocerebellar degeneration, motor neuron disease, and in some individuals, a bipolar form of psychosis.

Individuals with adult-onset disease display progressive muscle wasting, weakness, muscle twitching, and poor articulation of words. There can be tremendous variability in the degree and onset of symptoms within the same family. For instance, psychosis may be severe by age 20 in one individual, whereas another family member may only exhibit neuromuscular findings into their 50s or 60s.

Inheritance Pattern:
Chronic Hexosaminidase A Deficiency is an autosomal recessive disorder.

Diagnosis and Testing:
Patients and carriers of Chronic Hexosaminidase A Deficiency can be identified by a simple blood test that measures the enzymatic activity of beta-hexosaminidase A in blood or tissue samples.

Carrier detection can also be performed for males, females and for pregnant females to determine carrier status of Chronic Hexosaminidase A Deficiency. A measure of the enzyme hexosaminidase A (Hex-A) is taken using white blood cells or blood. It is a highly accurate and inexpensive procedure for determining one’s carrier status.

Life Expectancy:
Because the chronic form Hexosaminidase A Deficiency was discovered recently, prognosis for this type of the disease is not completely known.

Treatment:
For individuals with Chronic Hexosaminidase A deficiency who have psychiatric manifestations, conventional antipsychotic or antidepressant therapy may be used.  For older individuals who have psychiatric manifestations, the response to these therapeutic methods often has variable outcomes.

Treatment with lithium salts and electroconvulsive therapy has been reported to be beneficial in lessening episodes of psychotic depression.