Gaucher Disease

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The genetic disease, Gaucher's disease, causes a disorder of the lipid metabolism. Through this sphingolipidosis (lysosomal storage disease) there can be found a accumulation of sphingolipids in cells.

Phenotypic description of the disease

There exist three phenotypic expressions of the Gaucher's disease. Dependent of the severe of the disease, the disease shows different symptoms. Also, the age at which the first symptoms appear, is in connection with the degree of illness.

Classification of types:

Type I: non-neuropathic

This type is the most common one. It can begin in any age but mostly in adulthood.This form is most commonly seen in people of Ashkenazi Jewish heritage. Symptoms, that may occur in type I:

• skeletal abnormalities, osteopenia (bone pain/fractures)
• hepatomegaly (enlarged liver)
• splenomegaly (enlarged spleen)
• ->anemia (decrease in healthy red blood cells)
• ->thrombocytopenia (greater susceptibility to bruising, which may mean you have a low number of blood platelets)
• pingueculae (yellow spots in your eyes)
• delayed puberty
• nosebleeds

Type II: acute infantile neuropathic

The second disease form starts at the infant stage and has the severest degree of illness. Especially the symptom of brain damage shows a rapid progress. Symptoms, that may occur in type II:

• symptoms of type I
• brain problems (mental retardation, dementia)
• Rigidity
• Seizures

Type III: chronic neuropathic

The Type III of Gaucher’s disease begins in childhood or adolescence. The disease progress is slower than in type II. But liver and spleen symptoms even more intense. Symptoms, that may occur in type III:

• Symptoms of type I
• brain problems (mental retardation, dementia)

Biochemical disease mechanism

The enzyme lysosomal glucocerebrosidase (beta-glucosidase, glucosylceramidase)catalyzes the breakdown of a cell membrane constituent of red and white blood cells, called glucosylceramide.

Macrophages which eliminate these cells cannot process glucosylceramide of the cell membranes. Therefore, the waste product accumulates in fibrils and turns into so called Gaucher cells (that resemble crumpled-up paper on light microscopy).

Type II and III: beta-glucosidase accumulates in the brain because of the turnover of complex lipids during brain development and formation of the myelin envelope of nerve cells.

Inheritance and incidence

• The disease befalls both females and males and is inherited in autosomal recessive manner. That means that if both parents carry the defect gene, their child (in each pregnancy) will be affected (i.e. become the disease) with 1:4 chance.

• According to National Gaucher Foundation (USA) nearly 1 person in 20,000 has Gaucher's disease.
• About 1 in 100 humans in general population of USA is a carrier of Gaucher's most common type - type I, which gives a prevalence of 1 in 40,000. The carrier rate is much higher among Ashkenazi Jews: around 1 in 15, with birth incidence 1 in 450.
• Type II Gaucher's disease does not seem to be preferentially represented by a specific ethnic group.
• Type III Gaucher's disease occurs most frequently in the northern Swedish region of Norrbotten. The incidence is 1 in 50,000 there.