Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Gaucher Disease [E75.2]

OMIM numbers: 608013, 230800, 230900, 231000, 231000, 606463 (GBA)

Dipl.-Biol. Christine Nitsch, Dipl.-Biol. Birgit Busse

Scientific Background

Gaucher disease is an inherited autosomal recessive disease belonging to the group of lysosomal storage diseases. Through reduced activity of the enzyme 1 ß-glucocerebrosidase, there is disruption in the glycogen degradation in the lysosomes. This is caused by mutations in the GBA gene.

The enzyme defect causes a progressive, systematic accumulation of glucocerebroside, or glucosylsphingosine, in lysosomes of reticuloendothelial cells. Predominantly macrophages and monocytes are affected, although it can also lead to accumulation in the neurons. The increasing storage caused macrophages to grow in size and become Gaucher cells which are deposited in various organs. The clinical presentation of Gaucher disease is characterized by Gaucher cells seen particularly in the spleen, liver and bone marrow.

There are three types of Gaucher disease, grouped according to symptoms:

  • type 1: chronic, non-neuronopathic form,
  • type 2: acute, neuronopathic form,
  • type 3: chronic neuronopathic form.

Type 1 is the most commonly occurring form and can appear at any age, but primarily in adulthood. The course of disease is variable. Symptoms include splenomegaly, hepatomegaly, (pan)cytopenia, coagulation disorders, pinguecula, bone swelling, bone pain and pathological fractures.

The acute neuronopathic form (type 2) is characterized by CNS impairment in addition to non-neuronopathic symptoms. Hepatomegaly and anemia have been seen. Those affected usually die within the first 2 years of life.

Type 3 occurs mostly in teenagers and young adults, displays variable symptoms similar to type 1, and in addition, a progressive encephalopathy with seziures, oculomotor apraxia, ataxia and dementia.

Before molecular genetic testing of the GBA gene, chitotriosidase (a product of activated macrophages) should be measured and the enzyme activity of ß-glucosidase in leukocytes determined.

The disease is inherited in an autosomal recessive pattern, i.e. both alleles must be affected for clinical expression of the enzyme deficiency. With a worldwide incidence of approximately 1:40,000, it is a rare disease, although it can occur frequently in particular ethnic groups (e.g., Ashkenazi Jews, Turkish population 1: 1,000). The possibility of enzyme replacement therapy for patients with type 1 and type 3 Gaucher disease in addition to symptomatic treatment has existed in Europe since 2006.