Gaucher disease type I

Synonyms

11

Overview

Type I (or non-neuropathic type) Gaucher disease is by far the most common form of the disease. Patients in this group usually bruise easily and experience fatigue due to anemia and low blood platelets. They also have an enlarged liver and spleen, skeletal disorders, and, in some instances, lung and kidney impairment. There are no signs of brain involvement. Symptoms can appear at any age.

Symptoms

Symptoms range from mild to severe and can appear at any time, from infancy to old age. Gaucher symptons may include:

  • anemia
  • fatigue
  • easy bruising and a tendency to bleed

 

An enlarged spleen and liver may also occur in Gaucher disease as well tas bone pain, degeneration and fractures. Bone disease may lead to neurologic problems such as compression of the spinal cord. Brown spots at the edges of the cornea (the front surface of the eye) are also a feature of type 1 Gaucher disease.

Causes

Gaucher type I disease is inherited in an autosomal recessive pattern, which means two copies of the gene must be altered for a person to be affected by the disorder. Mutation of the GBA gene (N370S homozygote) leads to deficiency of an enzyme, glucocerebrosidase, which is needed to break down a lipid called glucocerebroside. This fatty substance then accumulates in "Gaucher cells" which are found particularly in the liver, spleen, and bone marrow. Damage in these organs cause the symptoms of the disease.

Prevention

The disorder results when an individual inherits defective gene for the enzyme glucocerebrosidase from both parents.

So there is no known possible prevention, but genetic counseling is recommended for prospective parents with a family history of Gaucher disease. Testing can determine if parents carry the gene that could pass on the Gaucher disease. A prenatal test can also tell if the fetus has Gaucher syndrome.

Gaucher disease affects an estimated 1 in 50,000 to 1 in 100,000 people in the general population. Persons of Eastern and Central European (Ashkenazi) Jewish heritage are at highest risk for the disease.

Diagnosis

The doctor will perform a physical exam. The patient may have signs of liver and spleen swelling, bone changes, lung disease, eye movement problems, heart problems, or hearing loss.

The following tests may be performed:

  • Blood test to look for enzyme activity
  • Bone marrow aspiration
  • Biopsy of the spleen
  • MRI
  • CT
  • X-ray of the skeleton
  • Genetic testing

 

A definitive diagnosis is made with genetic testing. As there are numerous different mutations, sequencing of the beta-glucosidase gene is sometimes necessary to confirm the diagnosis. Prenatal diagnosis is available, and is useful when there is a known genetic risk factor.

A diagnosis can also be implied by biochemical abnormalities such as high alkaline phosphatase, angiotensin-converting enzyme (ACE) and immunoglobulin levels, or by cell analysis showing "crinkled paper" cytoplasm and glycolipid-laden macrophages.

Some lysosomal enzymes are elevated, including tartrate-resistant acid phosphatase, hexosaminidase, and a human chitinase, chitotriosidase. This latter enzyme has proved to be very useful for monitoring Gaucher's disease activity in response to treatment, and may reflect the severity of the disease

Prognosis

How well a person does depends on the subtype of the disease. The infantile form of Gaucher disease may lead to early death. Most affected children die before age 5. Adults with the type I form of the disease can expect normal life expectancy with enzyme replacement therapy.

Treatment

FDA-Approved Treatments:

  • Alglucerase injection FDA-approved indication: Long-term enzyme replacement therapy for children, adolescents and adult patients with a confirmed diagnosis of Type I Gaucher disease who exhibit signs and symptoms that are severe enough to result in one or more of the following conditions: a) moderate- 
  • Imiglucerase Enzyme replacement therapy in patients with type I Gaucher's disease. 
  • Taliglucerase alfa Use as long-term enzyme replacement therapy in patients with Type I Gaucher disease 
  • Miglustat Treatment of mild to moderate Type I Gaucher disease in adults for whom enzyme replacement therapy is not a therapeutic option (e.g., due to constraints such as allergy, hypersensitivity, or poor venous access). 

Resources

See Research Publications