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[edit | edit source]

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[edit | edit source]

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[edit | edit source]

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[edit | edit source]

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Diagnostic Tests/Lab Tests/Lab Values[edit | edit source]

  • Diagnosis of gaucher disease is focused on lab testing and clustering of clinical signs/symptoms. Gaucher disease is thought to be a possible diagnosis in individuals with an enlarged liver/spleen (hepatosplenomegaly), bone pain/abnormalities, the tendency to bruise and bleed very easily from low platelets, possible signs of neurological involvement and alterations in red blood cell levels.3


  • Laboratory testing includes blood work to determine the activity level of the enzyme glucocerebrosidase. Individuals diagnosed with Gaucher disease have extremely low levels of glucocerebrosidase activity. Another lab test performed involves analysis of the DNA. This analysis looks for the GBA gene and the four most frequent GBA mutations.3


  • When the GBA gene mutation is known in a family, DNA testing should be completed and used to correctly recognize any carriers.3

Etiology/Causes[edit | edit source]

  • Gaucher disease is caused by a mutated gene called GBA. It is inherited in an autosomal recessive way when a person has two copies of the genes that supply directions for constructing the enzyme, glucocerbrosidase.3 For healthy people, both genes work correctly.3 When one of the genes is not functioning appropriately the person becomes a carrier for the disorder.


  • Carriers do not have the disease because they have one functioning gene that creates adequate amounts of the enzyme for normal body function. When an individual inherits a mutated gene from each carrier parent, he or she then develops Gaucher disease.3


  • Carrier parents have a 1 in 4 or 25% chance to conceive a child born with the disease. They have a 1 in 2, or 50 % chance to have a child who is a carrier, and a 1 in 4, or 25% chance to produce a child who is neither has the disease or is a carrier.3

Systemic Involvement[edit | edit source]

The systems affected by Gaucher Disease include the following:

  • Digestive system due to the increase in size of the liver
  • Lymphatic system due to the increase in size of the spleen
  • Neurological system due to damage to the brain in types 2 and 3

Medical Management (current best evidence)[edit | edit source]

  • Enzyme replacement therapy is 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
  • Bone marrow transplantation can help reverse the non-neurological effects of type 1, but has a high death rate due to defective donor matches.1
  • There is no effective treatment for brain damage with types 2 and 3.1
  • 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.


Physical Therapy Management (current best evidence)[edit | edit source]

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Alternative/Holistic Management (current best evidence)[edit | edit source]

  • There are not any scientifically proven substitutes to the standard treatments of enzyme replacement therapy, substrate replacement therapy, medication, and bone marrow transplant, but the National Gaucher Foundation finds that daily moderate exercise may help ease some of the symptoms associated with the disease. These may include improvement in bone health and abdominal core strength.

Differential Diagnosis[edit | edit source]

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Case Reports/ Case Studies[edit | edit source]

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Resources
[edit | edit source]


National Gaucher Foundation                               

   2227 Idlewood Road, Suite 12
   Tucker, GA 30084
   [email protected]
   Tel: 800-504-3189
   Fax: 770-934-2911

    http://www.gaucherdisease.org


National Organization for Rare Disorders (NORD)   

    P.O. Box 1968
    (55 Kenosia Avenue)
    Danbury, CT 06813-1968
    [email protected]
    Tel: 203-744-0100 Voice Mail 800-999-NORD (6673)
    Fax: 203-798-2291

     http://www.rarediseases.org


National Human Genome Research Institute – Learning About Gaucher Disease

   1 http://www.genome.gov/25521505 1


National Institute of Neurological Disease and Stroke – Gaucher’s Disease Information

   2 http://www.ninds.nih.gov/disorders/gauchers/gauchers.htm 2

Recent Related Research (from Pubmed)[edit | edit source]

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References[edit | edit source]

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