GM1 Gangliosidosis

What is GM1 gangliosidosis?

GM1 gangliosidosis is a rare disease that causes molecules to build up, irreversibly damaging nerve cells in your brain and spinal cord. You inherit a gene change (mutation) from each of your parents that causes this disorder. Symptoms may appear in infancy, childhood or adulthood. It is a type of lysosomal storage disorder. Unfortunately, there isn't a cure.

What is a lysosomal storage disorder?

Lysosomal storage disorders are a type of inherited metabolic disorder that affect how your metabolism works. Your metabolism helps convert food into energy and get rid of toxins. There are about 50 different lysosomal storage diseases, including Tay-Sachs disease.

Lysosomal refers to lysosomes: small components in cells that contain enzymes. These enzymes help your body break down large molecules like fats and sugars. When these large molecules enter cells, the enzymes change them into simpler ones. When you have a lysosomal storage disorder, your enzymes can’t perform this task. As a result, molecules build up, and your body starts to abnormally store them. This is where the term “storage disorder” (or storage disease) originates.

Lysosomal storage disorders like GM1 gangliosidosis are progressive diseases. The symptoms get worse as more molecules accumulate in your body.

What are the types of GM1 gangliosidosis?

GM1 gangliosidosis is a congenital disease, which means the gene change that causes it is present at birth. However, symptoms may not appear until later in life. Healthcare providers classify GM1 gangliosidosis into types based on when symptoms first appear. There’s often an overlap of symptoms and timing.

Types of GM1 gangliosidosis include:

• Classic infantile (type 1): Symptoms are usually evident by the time a baby is 6 months old. This type progresses quickly.
• Juvenile (type 2): Symptoms typically appear when a child is between 1 and 5 years old. Disease progression is slower than type 1.
• Adult (type 3): Symptoms can appear as early as age 3 and as late as age 30. This type progresses slower than the others.

How common is GM1 gangliosidosis?

GM1 gangliosidosis is extremely rare. It affects approximately 1 in every 100,000 to 200,000 people worldwide.

What causes GM1 gangliosidosis?

A change in the GLB1 gene causes GM1 gangliosidosis. This gene helps make an enzyme called beta-galactosidase found in lysosomes. The enzyme breaks down molecules like GM1 ganglioside, which plays a critical role in how nerve cells function in your brain.

The gene change prevents your body from breaking down GM1 ganglioside. The molecules start to build up in tissues and organs. The disease causes irreversible damage to cells in your nervous system, particularly your brain and spinal cord.

Who is at risk for GM1 gangliosidosis?

In order to develop GM1 gangliosidosis, you must inherit a changed GLB1 gene from each parent. In this case, your parents are carriers of the gene change, but they don’t actually have the disease. Your healthcare provider may refer to this as an autosomal recessive disorder.

Even when both parents are carriers of the GLB1 gene mutation, their children may or may not be affected. When the disease occurs, it’s usually the same type that has affected past generations.

When both parents have the gene change, each of their children has a:

• 1 in 4 chance of not getting the mutated gene (no risk of disease).
• 1 in 4 chance of developing GM1 gangliosidosis.
• 1 in 2 chance of being a carrier who doesn’t develop the disease.

Any family may have this genetic mutation, but people of Japanese descent are more likely to develop type 3.

What are the symptoms of GM1 gangliosidosis?

Symptoms of GM1 gangliosidosis vary depending on the type. The types share some of the same symptoms.

Signs of infantile (type 1) GM1 gangliosidosis:

• Distended abdomen.
• Enlarged spleen and enlarged liver.
• Extreme startle response to loud noises.
• Hearing loss.
• Red spots on the eyes and loss of vision.
• Regression of developmental milestones.
• Seizures.
• Stiff joints or skeletal abnormalities.
• Weak muscle tone (hypotonia).

Signs of juvenile (type 2) GM1 gangliosidosis:

• Ataxia (coordination and balance problems).
• Corneal disease (clouding).
• Difficulty swallowing (dysphagia).
• Dystonia (excessive muscle contractions).
• Loss of cognitive function or thinking skills.
• Problems with speech (dysarthria).
• Seizures.

Signs of adult (type 3) GM1 gangliosidosis:

• Muscle weakness or atrophy.
• Corneal disease (clouding).
• Dystonia.
• Noncancerous (benign) skin lesions.

How is GM1 gangliosidosis diagnosed?

If this disease runs in your family, a prenatal test can determine whether a developing fetus has the gene change. The pregnant person may get a genetic amniocentesis or a chorionic villus sampling (CVS) test to look for cells that have the changed gene.

These tests can diagnose the condition in infants to adults:

• Enzyme assay: This test measures beta-galactosidase enzymes in your blood.
• Molecular genetic test: This blood test examines DNA sequences to identify the GLB1 gene mutation. You inherit your DNA (deoxyribonucleic acid) from your parents.
• Newborn screenings: Some states include enzyme tests for lysosomal storage disorders as part of routine newborn care in the hospital.

What are GM1 gangliosidosis treatments?

There isn’t a medication, procedure or cure for GM1 gangliosidosis. Treatments focus on minimizing symptoms unique to the individual to improve quality of life. For instance, a ketogenic diet (keto diet) for epilepsy and anticonvulsant drugs like gabapentin may alleviate seizures.

However, medical researchers are actively looking for new ways to treat and stop the disease. You or your child may be able to participate in a clinical trial to try promising new therapies still in development. These therapies may include:

• Enzyme enhancement or enzyme replacement therapy.
• Gene therapy.
• Stem cell transplants (also called bone marrow transplants).
• Substrate reduction therapy to change the molecules and stop the disease process.

Can you prevent GM1 gangliosidosis?

If you carry the mutated gene that causes GM1 gangliosidosis, a genetic counselor can discuss options for lowering the odds of passing it on to your children. For instance, you may use preimplantation genetic diagnosis (PGD) to identify embryos that don’t carry the mutated gene. Your healthcare provider implants the healthy embryos using in vitro fertilization (IVF). PGD guarantees your child won’t be a carrier or develop the disease.

What is the outlook for someone with GM1 gangliosidosis?

Symptoms of GM1 gangliosidosis get progressively worse over time. The life expectancy and quality of life for someone with GM1 gangliosidosis varies depending on the type:

• Babies with type 1 (classic infantile) may live to age 2.
• Children with type 2 (juvenile) may live into mid-childhood or early adulthood depending on their age at the onset of symptoms.
• People with type 3 (adult) have shortened lifespans that vary depending on their age at the onset of symptoms, as well as symptom type and severity.

When should I call the doctor?

Call your healthcare provider if you or your child experiences:

• Balance or gait (walking) problems.
• Difficulty breathing, swallowing or speaking.
• Hearing or vision changes.
• Red spots on the eyes.
• Seizures.

What should I ask my provider?

You may want to ask your healthcare provider:

• What type of GM1 gangliosidosis do I (or my child) have?
• What medications can ease symptoms?
• What steps can we take at home to ease symptoms?
• What medical specialists should we see?
• Should I look for signs of complications?
• Should my family get tested for the gene mutation?

A note from Cleveland Clinic

GM1 gangliosidosis is a rare inherited disease that prevents your body from breaking down fat and sugar molecules. It’s a type of lysosomal storage disorder. As the molecules build up, you experience symptoms like seizures, balance problems and difficulty swallowing. In order to develop this disease, you must inherit a copy of the gene mutation that causes it from both your mother and father. Treatments focus on easing specific symptoms. There isn’t a cure, but there are clinical trials underway for new therapies. Your healthcare provider can discuss ways to lower the chances of passing the gene mutation to future generations.