Gaucher Disease (GD)

What are the other Names for this Condition? (Also known as/Synonyms)

• Cerebroside Lipidosis Syndrome
• Glucocerebrosidase Deficiency
• Kerasin Histiocytosis

What is Gaucher Disease? (Definition/Background Information)

• Gaucher Disease is an inherited genetic disorder that can affect a variety of organs and body systems. Some individuals have mild signs and symptoms, while in others it may be severe
• There are 3 types of Gaucher Disease and these include:
  • Type I Gaucher Disease: It is the most common type. In this type, the central nervous system (CNS) consisting of the brain and spinal cord is not affected. Hence, it is also called Non-Neuronopathic Gaucher Disease
  • Type II and Type III Gaucher Disease: In type II and type III conditions, the CNS can be affected, and hence, these types are called neruonopathic types
• Occasionally, babies born with Gaucher Disease do not survive beyond infancy due to the severity of the signs and symptoms. This type is called Perinatal Lethal form of Gaucher Disease
• Sometimes, the heart can be predominantly affected resulting in improper functioning of the heart, due to calcification. This type is called Cardiovascular Type of Gaucher Disease

Who gets Gaucher Disease? (Age and Sex Distribution)

• The incidence of Gaucher Disease varies from 1 in 50,000 to 1 in 100,000 among the general population
• Both male and female genders are equally susceptible to the disorder
• All racial and ethnic groups may be affected, but Gaucher Disease is seen to affect Ashkenazi Jews (who are present in parts of Europe) at a very high incidence rate

What are the Risk Factors for Gaucher Disease? (Predisposing Factors)

• A positive family history of Gaucher Disease is the only known risk factor for the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Gaucher Disease? (Etiology)

• Gaucher Disease is a genetic disorder that is inherited in an autosomal recessive pattern
• In this disorder, there are genetic mutations in the GBA gene, which is responsible for the production of an enzyme beta-glucocerebrosidase
• The abnormal mutation greatly diminishes the enzyme activity, without which certain harmful substances get accumulated in the body tissues and organs to toxic levels. This results in the characteristic signs and symptoms of Gaucher Disease

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Gaucher Disease?

The signs and symptoms of Gaucher Disease, which can vary from mild to severe, include the following:

• Enlarged liver (hepatomegaly) and enlarged spleen (splenomegaly)
• Decreased blood cell count causing anemia
• Individuals with anemia may have fatigue, low energy, and decreased exercise tolerance
• Decreased platelet count can cause easy bruising
• Bone and joint pain, arthritis of joints, weakening of the bones resulting in easy fractures
• Lung disease can cause breathing difficulties

In Type I Gaucher Disease, there are no symptoms related to the central nervous system. Type II and Type III Gaucher Disease have symptoms of the nervous system such as:

• Seizures
• Abnormal eye movements
• Decreased IQ levels

Type II Gaucher Disease usually affects infants and can be life-threatening. Also, the symptoms in Type III Gaucher Disease progresses more slowly than the type II condition.

In the Perinatal Lethal form of Gaucher Disease, severe signs and symptoms occur, resulting in either stillbirths or severe complications in infants. In this form, the indications include:

• Dry, scaly skin
• Liver and spleen enlargement
• Severe neurological complications

In the Cardiovascular type of Gaucher Disease, the heart is primarily affected and the most common complication is improper functioning of the heart valves. The other signs and symptoms may include:

• Enlarged spleen
• Weak bones resulting in frequent and easy fractures
• Bone pain

It has to be also noted that individuals of Askenazi Jewish descent have more severe signs and symptoms than individuals of other races.

How is Gaucher Disease Diagnosed?

Gaucher Disease may be diagnosed using the following tools:

• Complete physical examination with evaluation of medical history. This includes screening of newborn babies with a family history of the disorder, which is very important
• Radiographic studies (for skeletal survey) such as CT and MRI scan of the affected regions
• Blood and bone marrow analysis
• Spleen biopsy
• Genetic tests and analysis
• Prenatal test to detect any abnormal mutations (if there is a family history of Gaucher Disease)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Gaucher Disease?

Complications due to Gaucher Disease include:

• Blood-related abnormalities
• Bone disorders such as loss of bone minerals leading to weak bones and joints, bone-death
• Massive liver and spleen enlargement
• Severe neurological dysfunction, epileptic seizures, and brain damage

How is Gaucher Disease Treated?

Gaucher Disease cannot be completely cured. Type I is more responsive to treatment than Type II and III. An individualized treatment regimen is planned and provided to improve the quality of life, based on the specific conditions/complications that develop:

• Enzyme replacement therapy prevents the onset of neurological complications; it also helps decrease bone defects and liver-spleen enlargement. However, this is excessively expensive and has to be continued for life
• Bone marrow transplantation helps reduce the intensity of blood and bone related abnormalities
• Blood transfusions to help control anemia
• The surgical removal of spleen, surgical replacement of joints (hip), and liver transplants are other options based on symptomatic development of the condition
• Medications are used to control seizures (antiepileptic drugs), infections (antibiotics), and bone damage (bisphosphonates)

How can Gaucher Disease be Prevented?

• Currently, there are no specific methods or guidelines to prevent Gaucher Disease, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Gaucher Disease
• Regular medical screening at periodic intervals with tests, scans and physical examinations are mandatory

What is the Prognosis of Gaucher Disease? (Outcomes/Resolutions)

• All forms of Gaucher Disease that manifests at birth, or during early infancy stages have poor prognosis; most children die before age 3-5 years
• Lifelong enzyme replacement therapy is required for Type I, which is onset during adulthood; individuals can have a normal life span
• Type II is the most fatal form; most children die of neurological impairment before age 3 years
• Type III has a late onset; however, with enzyme replacement infusions, life span may be extended into the early 30s
• Perinatal Lethal form of Gaucher Disease that affects infants at birth is usually fatal

Additional and Relevant Useful Information for Gaucher Disease:

There are voluntary organizations and support groups that provide help and understanding to the families and parents of the Gaucher Disease affected.