Gaucher Disease

By Pimpatchara Roongsug, Punika Suvimolpan, Phurinat Suandork

Edited by Hargun Champi, Torpud Choemcharoen

Gaucher disease is a genetic disorder, specifically a lysosomal storage disorder, characterized by a detrimental accumulation of fatty substances or sphingolipids in the liver, spleen, or bone marrow. This is due to the deficiency or malfunction of an enzyme that is responsible for breaking down those fatty substances. Consequently, there are negative impacts on various organs and tissues as well as their functions, such as the enlargement and dysfunction of the spleen and liver, increasing bone vulnerability, a higher probability of bone fractures, etc.

Gaucher Diseases are categorized into three types:

• Type 1: 

  • Early childhood to late adulthood. 

  • No cure, but treatable.

  • Low platelets in the blood, leading to a higher risk of getting bruises and fatigue.

  • Enlargement of liver and spleen. 

  • No brain or neurological disorder

• Type 2: 

  • Also known as acute infantile neuronopathic Gaucher disease

  • Age 3 to 6 months. 

  • Deadly, and in most cases only live up to 2 years old.

  • Central nervous system problems

• Type 3:

  • Skeletal health issues

  • Disorders in the eye movement

  • Seizures that developed to be more apparent or severe over time

  • Blood disorders

  • Respiratory problems

  • Enlargement of liver and spleen

Causes and  Symptoms

Gaucher disease (including all types) is an inherited metabolic disorder in an autosomal recessive pattern. An individual or a child will inherit Gaucher disease when receiving the recessive gene from both parents. Ultimately, gaucher disease is caused by the genetic mutation of the GBA gene, which is responsible for the production of glucocerebrosidase (GCase), an enzyme responsible for the breakdown of sphingolipids (fatty substances). Thus, those who lack GCase are prone to the accumulation of these fatty substances or sphingolipids in organs, bone marrow, and the brain, resulting in the damage of the organ functions, blood cells, and the fragility of the bones.

Symptoms of Gaucher disease can be different from person to person, and they may include a wide range of conditions, complications, and symptoms. Nonetheless, the majority of individuals who suffer from Gaucher disease are highly likely to experience various severity of the following symptoms:

• Arthritis, joint pain, and joint damage

• Osteonecrosis or avascular necrosis

• Osteoporosis, osteopenia, and increase in bone fragility

• Anemia

• Enlarged organs

• Bruising, bleeding, and clotting issues

• Fatigue

• Lung problems

For cases with higher severity, typically in types 2 and 3, symptoms may include neurological disorders and skin abnormalities of the following:

• Developmental delays and feeding difficulties (for babies with type 2)

• Cognitive challenges

• Eye problems

• Gross motor skills and coordination problems

• Seizures, muscle spasms, and quick, jerky movements

Risk Factors

Gaucher disease is a genetic disorder that includes some risk factors that can increase the development of the condition. The risk factors include

1. The main risk factor that individuals have to face without any inevitable outcome is a family history of having Gaucher disease. In cases where both parents are the carriers, the child will have a 25% chance of receiving the disease. 

2. Genetic disposition could be the second factor that increases the risk for Gaucher disease, having inherited two mutated copies of the glucocerebrosidase or GBA gene. Individuals who have this condition could cause the disease autosomal recessive.

3. Thirdly, If an individual and their partner were known as a carrier of the GBA gene mutation,  the risk of having a child with Gaucher disease is significantly higher.

Treatment

Even though there are no specific treatments to permanently cure Gaucher's disease, many methods can be used for relieving symptoms and preventing the immediate symptoms. There are various categories of treatments consisting of monitoring progression according to each individual. Common treatments include medications and medical procedures.

Medications:

1. Enzyme replacement doses: deficiency of enzymes can be replaced by artificial doses every half a month. However, there might be allergies due to changes in health conditions.

2. Miglustat: medication focusing on inhibiting the release of fatty acids, which triggers the symptoms of Gaucher disease. Due to reducing fatty acids, diarrhea and weight loss might be found in these groups of patients.

3. Eliglustat: Similar to Miglustat, these drugs decelerate the production of fatty acids in Gaucher disease.

4. Osteoporosis drugs: methods that enhance the creation of spongy bone affected by the disease.

Medical Procedure:

1. Bone Marrow Transplant: This procedure removes and replaces the diseased cells, transporting them through blood vessels. Afterwards, these cells will infuse into patients' bone marrow, responsible for reducing symptoms of Gaucher disease. The disadvantages of these methods involve a long-term recovery, which might reach a year or more.

2. Splenectomy:  Splenectomy or the surgical removal of the enlarged spleen caused by Gaucher disease. The disease accumulates a large amount of fatty acids, forcing the spleen to facilitate harder. Consequently, this will also prevent symptoms according to enlargement of the spleen including pain, anemia, and excessive bleeding. According to medical considerations, this procedure informs the last methods if other therapies are not effective for the patients.

Conclusion

Gaucher disease is a hereditary disorder resulting from the deficiency or lack of glucocerebrosidase (GCase), which is caused by the GBA gene mutation and the inheritance of these recessive genes. This leads to the buildup of fatty chemicals or sphingolipids in organs, causing enlargement and dysfunction. Symptoms may include skeletal problems, blood disorders, and abdominal and organ abnormalities. More severe cases may result in neurological disorders and skin abnormalities. While there is no designated treatment for a permanent cure, taking medications or medical procedures like organ transplant and removal surgery can help regulate, prevent, and relieve the symptoms of Gaucher disease.

Citation

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