GM1 Gangliosidosis

GM1 gangliosidosis, also called beta-galactosidase-1 deficiency, is a genetic disorder that progressively destroys nerve cells in the brain and spinal cord. The disorder is one of about 50 diseases classified as lysosomal storage disorders (LSD), where a genetic variation disrupts the normal activity of lysosomes in human cells.

What are lysosomes and what do they do?

Lysosomes contain specific proteins (enzymes) that are responsible for breaking down and recycling molecules such as fats and sugars. Individuals with a lysosomal storage disorder lack one of these necessary enzymes or do not have one of these enzymes in sufficient quantities to break down molecules for proper cell function. As a result, fats and sugars normally broken down by lysosomes can accumulate to toxic levels in the body’s cells and tissues, eventually leading to signs of disease.

What causes GM1 gangliosidosis in children?

GM1 gangliosidosis is caused by a mutation in the GLB1 gene, resulting in a deficiency in an enzyme called beta-galactosidase-1, which lysosomes require to properly break down large sugar molecules inside the body’s cells. This genetic condition is inherited in an autosomal recessive pattern, which means that an affected child has received one defective copy of the GLB1 gene from each of their parents.

When symptoms of the disease are present at birth or before 6 months of age, it is referred to as infantile or type I GM1 gangliosidosis. If signs of the disorder occur in late infancy or early childhood, it is referred to as type II GM1 gangliosidosis. When symptoms are present in adolescence or adulthood the disease is referred to type III GM1 gangliosidosis.

What are the symptoms of GM1 gangliosidosis?

The severity of symptoms and the time at which they first present can vary greatly in GM1 gangliosidosis. In general, an earlier manifestation of symptoms, as occurs in infantile or type I GM1 gangliosidosis, is often part of a more severe and rapidly progressive disease. Signs and symptoms children with GM1 gangliosidosis may experience include:

• distinct facial features (coarse facial features)
• poor muscle tone (hypotonia)
• enlargement of the liver and spleen (hepatosplenomegaly)
• exaggerated startle reaction
• developmental regression
• skeletal abnormalities
• seizures
• visual impairment

Treatment for GM1 gangliosidosis

There are currently no approved therapies which reverse the effects of GM1 Gangliosidosis. Current approaches involve interdisciplinary collaboration to provide targeted management for specific symptoms.

How we care for GM1 gangliosidosis

At the Boston Children’s Lysosomal Storage Disorder (BoLD) Program, our team of providers is committed to the care of complex patients. As part of Boston Children’s Hospital, we are prepared to meet the challenge of providing multifaceted care by partnering with you and your child to deliver direct care in our BoLD clinic. We work with the broad array of world-class specialists at Boston Children’s to optimize the care we provide your child with GM1 gangliosidosis.