The gangliosidoses are a group of inherited metabolic diseases caused by a deficiency of the different proteins needed to break down fatty substances called lipids. Excess lipid materials build up to harmful levels in the central and peripheral nervous systems, particularly in nerve cells. These genetically different disorders occur when both parents pass along the same mutated gene that regulates these proteins. The GM1 gangliosidoses are caused by a deficiency of beta-galactosidase. Symptoms of early infantile GM1 (the most severe subtype, with onset shortly after birth) may include neurodegeneration, seizures, liver and spleen enlargement, coarsening of facial features, skeletal irregularities, joint stiffness, distended abdomen, muscle weakness, exaggerated startle response to sound, and problems with gait. About half of affected persons develop cherry-red spots in the eye. Children may be deaf and blind by age 1. Onset of late infantile GM1 is typically between ages 1 and 3 years. Symptoms include ataxia, seizures, dementia, and difficulties with speech. Adult GM1 strikes between ages 3 and 30, with symptoms that include muscle atrophy, corneal clouding in some patients, and dystonia. Non-cancerous skin blemishes may develop on the lower part of the trunk of the body. Adult GM1 is usually less severe and progresses more slowly than other forms of the disorder.
No specific treatment exists for the gangliosidoses. Anticonvulsants may initially control seizures. Other supportive treatment includes proper nutrition and hydration and keeping the airway open.
Children with early infantile GM1 often die by age 3 from cardiac complications or pneumonia. Children with Tay-Sachs disease often die by age 4 from recurring infection. Children with Sandhoff disease generally die by age 3 from respiratory infections.
Prepared by the National Institutes of Health