GM2 Gangliosidosis (Tay-Sachs)
GM2 Gangliosidosis (Tay-Sachs) is a disorder of sphingolipid metabolism. Sphingolipids are found throughout the body but play an important role in the nervous system, including in myelin sheaths and grey matter of the brain.
GM2 Gangliosidosis is an autosomal recessive disorder caused by a deficiency in the enzyme beta-hexosaminidase A (HEX A subunit) encoded at chromosome 15q23-q24. The clinical form of GM2 acute infatile form is Tay-Sachs disease, and is characterized by progressive weakness, loss of motor skills, decreased attentiveness, and increased startle response beginning between three and six months of age. Continued symptoms incude continued neurodegeneration, seizures, blindness, spasticity, eventual total incapacitation, and death, usually before age four years. There are later onset forms, including the juvenile (subacute), chronic, and adult-onset variants of the hexosaminidase A deficiencies 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.
Currently, there is no effective medical cure for the underlying disorder and symptoms are managed aggressively. Treatment is mostly supportive and directed to provide adequate nutrition and hydration, to manage infectious disease, to protect the airway, and to control seizures. Seizure control can usually be achieved using conventional anticonvulsant medications 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.
