Gaucher Disease - Causes, Types, Symptoms, Diagnosis, and Treatment

Introduction

Gaucher disease is a rare metabolic disorder caused by the deficiency of the enzyme glucocerebrosidase (GCase). The enzyme glucocerebrosidase metabolizes or breaks down a fatty substance called glucocerebroside. The fatty substance (glucocerebroside) accumulates in the liver, spleen, lungs, eyes, bones, and brain cells without the enzyme. The disease happens due to mutations in the GBA (glucosylceramidase beta [human]) gene responsible for enzyme production. The child inherits the mutated GBA gene from both parents. Gaucher disease is most common in the people of Eastern Europe (in Jews of Ashkenazi descent).

What Are the Causes of Gaucher Disease?

The most common cause is the gene mutation that produces the enzyme glucocerebrosidase (GCase). The absence of the enzyme affects various body parts, including the liver and spleen, bone marrow, and bones. It passes from the parents to their children and is identified as an autosomal recessive condition, which means the mutated gene has to be present in both parents.

What Are the Types of Gaucher Disease?

There are three types of Gaucher disease, categorized based on the presence or absence of early brain involvement.

Type 1:

• It is the most common type of Gaucher disease.

• About 95 percent of cases diagnosed are of type 1.

• The patients may have a swollen belly due to liver and spleen enlargement, anemia, easy bruising, weak bones, and fatigue.

Type 2:

• It is a rare type.

• There is severe neurological involvement in the first two years of life, and the child cannot make it beyond two years of age.

• There is irreversible brain damage in type 2 patients.

Type 3:

• Type 3 shows slow progress when compared to type 2.

• There is brain involvement along with multi-organ involvement as well.

• The patients have a typically short life span. However, some of them can make it into their 50s.

What Are the Symptoms of Gaucher Disease?

The symptom's severity varies among different patients. However, the significant symptoms include the following:

• Swollen Belly and Abdominal Pain: The fat gets accumulated in the cells at abnormally high levels that cause an enlargement of the liver and spleen.

• Anemia: Effects on the bone marrow decrease the RBC (red blood cells) production, these are necessary for carrying oxygen to different body parts.

• Easy Bruises: They occur due to a decrease in the platelet count that manifests as nose bleeds, bleeding from the gums, and injuries that fail to clot.

• Bone Pain: A decrease in the blood flow to the bones causes bone pain, sometimes referred to as a bone crisis.

• Avascular Necrosis (AVN): Parts of the bone do not receive necessary oxygen, leading to bone death that presents as arthritis, shoulder and hip problems, and greater fracture risk.

• Osteoporosis: Loss of calcium and mineral content from the bones leads to depletion in the volume of the bones, causing osteoporosis. Smoking, alcohol consumption, and an inactive lifestyle can increase the risk of osteoporosis in Gaucher disease patients.

• Bone Fractures: Spontaneous bone fractures occur due to weak bones.

• Joint problems: Joint pain and permanent joint damage occur in cases of osteoporosis.

• Nerve problems: Neurological symptoms include the following:

  • Challenges in feeding.

  • Delay in development.

  • Eye problems, especially during side-to-side eye movement.

  • Problems in coordination and motor skills.

  • Seizures.

  • Muscle spasms.

  • Cognitive problems that cause an emotional imbalance.

• Lung Problems: They occur due to fatty substances accumulating in the lungs that make it difficult for patients to breathe.

What Are the Complications of Gaucher Disease?

Patients with Gaucher disease exhibit certain complications after their 50s, which include:

1. Osteoporosis makes the bones very fragile due to decreased mineral content and fractures easily.

2. Parkinson’s disease ( a degenerative disorder that affects a patient’s mobility, stiffens the muscles, and causes tremors).

3. Blood (myeloma) and liver cancers affect the lifespan of patients.

How to Diagnose the Condition?

A diagnosis of Gaucher disease is necessary if the patient experiences symptoms like a swollen belly, bone pain, easy bruising, or anemia. Also, patients with a family history of the disease need to get themselves tested. The following are the diagnostic tests that commonly diagnose the condition:

• Blood Test: A blood test named the beta-glucocerebrosidase-leukocyte test (BGL test) is done to determine the blood levels of the enzyme glucocerebrosidase. Low levels of the enzyme indicate the presence of Gaucher disease.

• DNA Analysis Test: A DNA analysis detects the mutated GBA gene. The test done prenatally detects the four most common GBA genes responsible for the cause of the disease.

• Carrier Testing: Genetic testing identifies the potential carriers of the mutated gene. Carriers do not have the disease, but they can transfer it to their offspring.

What Are the Treatment Options?

Treatment reduces the chances for permanent damage to the organs and helps manage the symptoms. The two treatment approaches that are commonly followed include:

1. Enzyme Replacement Therapy (ERT): Patients need ERT every two weeks. A modified version of the GCase enzyme is administered through an intravenous (IV) route into the patient’s body. The modified enzyme functions in place of the deficient enzyme and reaches the target organs to reduce the damage. The treatment is done either at the doctor’s office or at home.

2. Substrate Reduction Therapy (SRT): In SRT, the fatty substance glucocerebroside produced by the body is removed directly without the GCase enzyme. The medicines are administered by oral route, making it preferable and convenient for the patient.

Other treatments that are employed to manage the symptoms include:

• Blood transfusions in cases of severe anemia and decreased platelet count.

• Removal of the spleen when there is an abnormal enlargement of the spleen.

• Orthopedic surgery for joint replacement.

• Symptomatic pain relief by prescribing pain medications.

Treatment helps patients with type 1 manage the symptoms efficiently. In type 2, due to severe brain damage, the children cannot survive beyond two years. In type 3, the patients can make up to 20 or 30 years. The other symptoms can be managed but not be an improvement in neurological functioning or prevention of brain damage.

Conclusion:

Gaucher disease cannot be prevented. However, early diagnosis and treatment can lower the severity of symptoms and better the quality of life. In addition, if the screening test detects that a person is a carrier of the gene and plans to start a family, a genetic counselor may be of great help to plan things appropriately and reduce the chances of passing the gene to the child.