Generalized Gangliosidoses

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 the enzyme beta-galactosidase.  Signs of early infantile GM1 gangliodisosis  (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, 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 gangliosidosisis typically between ages 1 and 3 years. Signs include ataxia, seizures, dementia, and difficulties with speech. Adult GM1 gangliosidosis 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.The GM2 gangliosidoses include Tay-Sachs disease and its more severe form, called Sandhoff disease, both of which result from a deficiency of the enzyme beta-hexosaminidase. Symptoms begin by age 6 months and include progressive mental deterioration, cherry-red spots in the retina, marked startle reflex, and seizures.  Children with Tay-Sachs may also have dementia, progressive loss of hearing, some paralysis, and difficulty in swallowing that may require a feeding tube. A  rarer form of the disorder, which occurs in patients in their twenties and early thirties, is characterized by an unsteady gait and progressive neurological deterioration. Additional signs of Sandhoff disease include motor weakness, early blindness, spasticity, muscle contractions, an abnormally enlarged head, heart murmurs, doll-like facial features, and an enlarged liver and spleen.