Generalized gangliosidoses

• Article
• 2021-03-10

Gangliosidoses are a group of hereditary metabolic diseases caused by a lack of the various proteins needed to break down fatty substances called lipids. Excessive build-up of these fatty materials (oils, waxes, steroids, and other compounds) can cause permanent damage to the cells and tissues in the brain and nervous system, especially in nerve cells. There are two different groups of gangliosidoses that affect men and women equally.

The GM1 gangliosidoses are caused by a deficiency of the enzyme beta-galactosidase and have 3 clinical subtypes:

• GM1 early infantile gangliosidosis (the most severe subtype, which begins shortly after birth) has symptoms such as degeneration of nerve function, seizures, enlargement of liver and spleen, facial coarseness, skeletal irregularities, joint stiffness, abdominal distension, muscle weakness, exaggerated startle reaction, and trouble walking. About half of those affected develop cherry red spots in the eye. Children can be deaf and blind by the age of 1 year.
• Onset of GM1 late infantile gangliosidosis, usually between the ages of 1 and 3 years. Signs include an inability to control movement, seizures, dementia, and speech problems.
• Adult GM1 gangliosidosis strikes between the ages of 3 and 30 years, with symptoms such as muscle wasting, cornea clouding, and dystonia (persistent muscle contractions causing twisting and repetitive movements or abnormal postures). Non-cancerous patches of skin can develop on the lower trunk of the body. Adult GM1 tends to be less severe and progresses more slowly than other forms of the condition.

The GM2 gangliosidoses include Tay-Sachs disease and its more severe form, Sandhoff's disease, both of which are due to a deficiency of the enzyme beta-hexosaminidase. Symptoms begin at 6 months of age 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 hearing loss, some paralysis, and difficulty swallowing, which may require a feeding tube. A rarer form of the condition, occurring in individuals in their twenties and early thirties, is characterized by unstable gait and progressive neurological deterioration. Additional signs of Sandhoff's disease include weakness in nerve signaling that causes muscles to contract, early blindness, spasticity, muscle contractions, abnormally enlarged head,

Therapy

Prognosis

Children with early infantile GM1 often die of heart complications or pneumonia at age 3. Children with early Tay-Sachs disease may eventually need a feeding tube and often die of a recurrent infection at age 4. Children with Sandhoff's disease usually die of respiratory infections by the age of 3.

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