Gaucher Disease

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Original Editors - Sarah Ansburg from Bellarmine University's Pathophysiology of Complex Patient Problems project.

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Definition/Description

An autosomal recessive inherited genetic disorder of metabolism in which a dangerous level of a fatty substance called glucocerebroside collects in the liver, spleen, bone marrow, lungs, and at times in the brain. Gaucher disease is caused by mutations in a gene called GBA. Changes in the GBA gene cause low levels of glucocerebrosidase.³ An individual with this disorder inherits a mutated copy of the GBA gene from each of his or her parents. Signs and symptoms of this disease can vary broadly among individuals and types.¹

Prevalence

Gaucher disease occurs in about 1 in 50,000 to 100,000 individuals in the overall general population. Type 1 is the most common form and is frequent among individuals who are of Ashkenazi Jewish ancestry. Type 1 is seen in 1 in 500 to 1000 people of this type of Jewish descent and roughly 1 in 14 Ashkenazi Jews is a carrier. Type 2 and 3 of this disease are not as common.²

Characteristics/Clinical Presentation

Signs and symptoms for this disorder vary greatly upon the type of the disorder and the individual themselves.

These are the following types and their presentations.

Type	Presentation
Type 1	Most common form of this condition and is named Non-neuronopathic Gaucher Disease due to the lack of involvement of the brain and spinal cord.2 Symptoms at this stage can range from very mild to severe at times and can develop at any age. Chief signs and symptoms may include enlargement of the spleen and liver (hepatosplenomegaly), a decrease in blood platelets causing, bruising (thrombocytopenia), lung disease, decrease in number of red blood cells (anemia), and bone defects such as deep pain felt in the bone, arthritis and fractures.2
Type 2	Classified as a neuropathic form of the disease due to its involvement of the brain and spinal cord (central nervous system).2 At this stage, liver and spleen enlargement can be evident as early as 3 months of age. Individuals may have substantial brain damage, seizures, abnormal eye movements and usually die prior to the age of 2.1
Type 3	Type 3 is also categorized as a neuronopathic disorder because it also affects the central nervous system, but progresses at a slower rate than type 2. At this stage, spleen and liver magnification is unpredictable, and brain association including seizures steadily become evident.1 Key signs and symptoms can include eye movement disorders, blood disorders, and skeletal abnormalities.1
Perinatal Lethal Form	This category causes life-threatening problems beginning prior to birth or in infancy.2 Elements of this category may include significant swelling caused by fluid accumulation before birth (hydrops fetalis), dry skin (ichthyosis) enlarged spleen and liver, distinct facial features; and severe neurological problems. Most infants with this form only survive for a few days after birth.2
Cardiovascular Type	This form mainly affects the heart. It causes the heart valves to harden or calcify. Individuals with this form may also have eye abnormalities, swelling of the spleen and bone disease.2

Associated Co-morbidities

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Medications

Type	Description
Enzyme Replacement Therapy	Utilized for individuals with types 1 and 3 of the disease. Enzyme therapy works by decreasing skeletal abnormalities, decreasing liver and spleen size/inflammation, and reverses other symptoms of the disorder, including abnormal blood counts. The treatment includes a modified form of the glucocerbrosidase by IV infusion every two weeks.3 Enzyme therapy has no effects on the neurological aspects of the disorder.3
Substrate Reduction Therapy (SRT)	Slows the build-up of unwanted fatty substance in Gaucher cells. Lysosomes then are able to try to catch up and eliminate the extra fatty substance.4 SRT is taken orally by mouth every day in pill form.4 It provides another option to enzyme replacement therapy.
Bone Marrow Transplantation	Help reverse the non-neurological effects of type 1, but has a high death rate due to defective donor matches.1

Diagnostic Tests/Lab Tests/Lab Values

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Etiology/Causes

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Systemic Involvement

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Medical Management (current best evidence)

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Physical Therapy Management (current best evidence)

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Alternative/Holistic Management (current best evidence)

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Differential Diagnosis

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Case Reports/ Case Studies

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Resources

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Recent Related Research (from Pubmed)

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References

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