Hexosaminidases A and B deficiency

Hexosaminidases A and B Deficiency is a rare genetic disorder affecting the body's ability to break down certain fats, leading to a buildup that can damage the nervous system and other organs. This condition is categorized under the broader group of lysosomal storage diseases. It primarily involves deficiencies in the enzymes Hexosaminidase A and Hexosaminidase B, which play critical roles in the degradation of GM2 gangliosides, substances found in nerve cell membranes. The deficiency of these enzymes leads to the accumulation of GM2 gangliosides, particularly in neurons, causing progressive neurological deterioration.

Causes

Hexosaminidases A and B deficiency is caused by mutations in the HEXA gene for Hexosaminidase A deficiency, also known as Tay-Sachs disease, and the HEXB gene for Hexosaminidase B deficiency, known as Sandhoff disease. These genetic mutations are inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder.

Symptoms

The symptoms of Hexosaminidases A and B deficiency vary depending on the specific enzyme deficiency but generally include muscle weakness, motor skill regression, seizures, vision and hearing loss, intellectual disability, and paralysis. Symptoms typically begin in infancy or early childhood and progress over time.

Diagnosis

Diagnosis of Hexosaminidases A and B deficiency involves a combination of clinical evaluation, family history, and genetic testing. Enzyme assay tests can also be conducted to measure the activity levels of Hexosaminidase A and B in blood, fibroblasts, or leukocytes.

Treatment

There is currently no cure for Hexosaminidases A and B deficiency. Treatment focuses on managing symptoms and improving the quality of life. This may include medications to control seizures, physical therapy to maintain mobility, and nutritional support. Gene therapy and enzyme replacement therapy are areas of ongoing research.

Prognosis

The prognosis for individuals with Hexosaminidases A and B deficiency varies depending on the severity of the enzyme deficiency and the age at which symptoms begin. Early-onset forms of the disease, particularly Tay-Sachs disease, often result in early death, while late-onset forms may allow for a longer lifespan with management of symptoms.