What is Gaucher?


Gaucher is one of the most common, frequently occurring Lysosomal Storage Disorder (LSD). LSDs are genetic disorders due to the lack of specific enzymes which break down lipids (fats) or carbohydrates (sugars) in the body. There are more than 40 types of LSDs. Like most LSDs, Gaucher occurs in up to 1 in 40,000 live births each year. Gaucher is most prevalent among the Ashkenazi Jews.

Gaucher disease is due to the lack of key enzyme glucocerebrosidase (GCase) which breaks down a lipid (fat) known as glucocerebroside. Since the body cannot break down this type of fat, it leads to dangerous accumulation in the spleen, liver and bone marrow which can be fatal.

Currently, there is no cure for Gaucher and treatment involves management of the condition with enzyme replacement therapy, medications and surgeries. Research for gene therapy is in progress and has been giving positive results in clinical trials using the adeno-associated virus and lentiviral vector. CRISPR-CAS9 is another possibility for a permanent cure. (https://www.gaucherdisease.org/blog/close-cure-gaucher-disease/).

Types of Gaucher


There are three major types of Gaucher based on the disease affecting brain development:

  • Type 1 - is the most common form of Gaucher especially in Western countries and 95% of those affected have this type. This type does not affect brain development and is treatable with enzyme replacement therapy (ERT).
  • Type 2 - is a rare and more severe form of Gaucher and affects brain development. This form of Gaucher is untreatable and is usually fatal within the first 2 years of birth.
  • Type 3 - is the most common type worldwide. Type 3 falls somewhere between type 1 and type 2 in severity. Some neurological symptoms do occur in type 3. However, with regular ERT patients with this type can live up to 60 years of age.

Patterns of Inheritance


Patterns of Inheritance
Gaucher is an autosomal recessive condition
Image Source: Pixabay

Gaucher is an autosomal recessive disorder which means both parents have the carrier gene with 25% chance of each child having the disease.

Gaucher is caused by a mutation in a single gene known as GBA.

A child with Gaucher inherits two copies of the mutated GBA gene from each parent and hence expresses the disease.

Signs and Symptoms


Signs and symptoms of Gaucher vary among individuals. These include:

  • enlargement of spleen and liver (splenomegaly or hepatomegaly) anemia
  • easy skin bruising caused by low platelet count
  • bone weakness leading to fractures

Diagnosis


If the pediatrician or orthopedician suspects Gaucher, he/she will usually take a family history and history of the child’s symptoms. Some of the tests that are used to diagnose MD include:

  • biochemical tests - to measure the activity level of the enzyme glucocerebrosidase. Individuals with Gaucher will have low levels of this enzyme activity.
  • molecular test - DNA tests like Next Generation Sequencing (NGS) to locate the exact mutation causing the form of Gaucher. This test is basically a DNA analysis of the GBA gene.

Please see list of specialized genetic testing centres

diagnosis
Gaucher can be diagnosed with biochemical or molecular tests
Image Source: Pixabay

Treatment and Management


Currently, no permanent cure is available for Gaucher. Treatment is aimed at preventing complications and enabling independent living. An interdisciplinary team of doctors including pediatricians, neurologists, orthopedicians, pulmonologist, cardiologist and physiotherapists will be required to take care of the clinical needs of the child/adult. In the early stages when just diagnosed, it is important to immediately start ERT treatment to prevent further deterioration and prevent organ damage.

ERT involves balancing low levels of GCase with external enzymes like Imiglucerase or Velaglucerase. This is an intravenous (IV) infusion every 2 weeks which can even be taken at home. ERT helps in reducing symptoms like hepatosplenomegaly, bone weakness and low platelet counts.

Another modality of treatment known as Substrate Reduction Therapy or SRT is an oral medication that decreases the amount of glucocerebroside production in the body thereby reducing the excess buildup

Living with Gaucher


Children and adults with Gaucher can participate in all life activities and must be encouraged to go to regular schools, colleges and participate in social activities.

Genetic counselling and psychosocial counselling must be made available whenever required with other supportive measures.

Look up our list of patient organizations in India for help and support

Living with Gaucher
Children must be encouraged to engage in physical activities
Image source: Pixabay

Prenatal Testing and Gaucher


If there is a known case of Gaucher in the family, it is absolutely essential for closest female relatives like siblings, uncles, aunts and cousins to test for carrier status.

If a woman with a carrier status is pregnant, prenatal test is essential to determine if the fetus has the disease mutation.

Look up our list of clinical geneticists and testing centres in India for help and support

Mail us on namitha@strandlf.org if you require any further information or want to contribute a resource for this page

Article and Journal Links:


Videos:


What is Gaucher?

https://www.youtube.com/watch?v=j_WcSgcK1Tw

Winner: My Daughter and Gaucher Disease

https://www.youtube.com/watch?v=QHkVRZZGh1M