Hexosaminidase A Deficiency.

Authors

Editors

In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Stephens K, editors.

Source

GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013.
1999 Mar 11 [updated 2011 Aug 11].

Excerpt

DISEASE CHARACTERISTICS:

Hexosaminidase A deficiency results in a group of neurodegenerative disorders caused by intralysosomal storage of the specific glycosphingolipid, GM2 ganglioside. The prototype hexosaminidase A deficiency is Tay-Sachs disease, also known as the acute infantile variant. Tay-Sachs disease is characterized by progressive weakness, loss of motor skills, decreased attentiveness, and increased startle response beginning between ages three and six months with progressive evidence of neurodegeneration including: seizures, blindness, spasticity, eventual total incapacitation, and death, usually before age four years. The juvenile (subacute), chronic, and adult-onset variants of hexosaminidase A deficiency have later onsets, slower progression, and more variable neurologic findings, including: progressive dystonia, spinocerebellar degeneration, motor neuron disease, and, in some individuals with adult-onset disease, a bipolar form of psychosis.

DIAGNOSIS/TESTING:

The diagnosis of hexosaminidase A deficiency relies on the demonstration of absent to near-absent beta-hexosaminidase A (HEX A) enzymatic activity in the serum or white blood cells of a symptomatic individual in the presence of normal or elevated activity of the beta-hexosaminidase B (HEX B) isoenzyme. Molecular genetic testing of HEXA, the only gene in which mutations cause hexosaminidase A deficiency, is used primarily to: (1) distinguish pseudodeficiency alleles from disease-causing mutations in healthy individuals with apparent deficiency of HEX A enzymatic activity identified in population screening programs; and to (2) identify the specific disease-causing mutations in an affected individual to allow for genetic counseling of at-risk family members.

MANAGEMENT:

Treatment of manifestations: Treatment is mostly supportive and directed to providing adequate nutrition and hydration, managing infectious disease, protecting the airway, and controlling seizures. Seizure control can usually be achieved using conventional antiepileptic drugs such as benzodiazepines, phenytoins, and/or barbiturates; but seizures are progressive and can change in type and severity. For individuals with adult-onset hexosaminidase A deficiency who have psychiatric manifestations, conventional antipsychotic or antidepressant therapy may be used. Prevention of secondary complications: Good bowel management to avoid severe constipation.

GENETIC COUNSELING:

Hexosaminidase A deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3. Heterozygotes (carriers) are asymptomatic. Heterozygotes are identified through testing of individuals with a positive family history or through population screening programs directed to people of Ashkenazi Jewish heritage. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible once the disease-causing mutations have been identified in the family; prenatal testing is also possible by assay of HEX A enzymatic activity.