Gaucher disease type 1
Gaucher disease is an inherited lysosomal storage disease. It is caused by a defect in the processing of a metabolite in the body which leads to its accumulation in the lysosome, and to damage to the spleen, liver, and bone marrow.
In Gaucher disease, a glycolipid (carbohydrate-attached lipid) called glucocerebroside accumulates in toxic levels in the different body tissues.
Epidemiology
Gaucher disease is the most common lysosomal storage disorder. The prevalence of this disease is 1 in 75,000 births worldwide. It has an especially high prevalence in people of Ashkenazi Jewish descent. Around two thirds of all people with Gaucher’s in the United States are Ashkenazi Jews.
Gaucher disease is divided into several types. Gaucher disease type 1 does not affect the brain and nervous system. The carrier frequency of this type among people of Ashkenazi Jewish descent is 1 in 12, but it is a lot rarer in other populations.
Genetic basis
In Gaucher disease, an enzyme called glucocerebrosidase is deficient. This enzyme is active in the lysosome and breaks down glucocerebroside. This substance is found in the membrane of various cells and is regularly synthesized in our body. The enzyme deficiency leads to the accumulation of this substance in the tissues and macrophages.
Gaucher disease has an autosomal recessive inheritance pattern. Two carrier parents can pass down the gene mutation to their children, the chances of a second child with this disease being born to two carrier parents is twenty-five percent. The mutated gene is coded to glucocerebrosidase and located on chromosome 1.
Dozens of gene mutations have been found to cause this disease, but several mutations are responsible for most cases. Among Ashkenazi Jewish people, the mutation c.1226A>G is responsible for most cases of the disease.
Signs and symptoms
Irregular storage causes an accumulation of macrophages and glycolipids in the spleen, liver, and bone marrow. These are the main organs affected in Gaucher disease type 1. The accumulation in these organs causes an acute inflammatory reaction of the cells in the tissues.
Unlike Gaucher disease type 2, that causes severe brain damage in infants, people with Gaucher type 1 may only be diagnosed as adults and in these cases the disease can be almost asymptomatic.
People with type 1 may also suffer from impairments in the production of blood cells. They sometimes suffer from bleeding issues and irregular clotting. Other symptoms include fatigue, anemia, and developmental impairments during adolescence.
The enlarged spleen and liver can cause early satiety (as a result of the pressure to the stomach), abdominal pain and discomfort, and more.
Diagnosis
Gaucher disease diagnosis includes two main methods: assessment of the defective enzyme, and genetic testing. Enzyme tests may point to an inactivity of the enzyme glucocerebrosidase. Genetic testing is especially effective when searching for a known mutation that runs in the family or is characteristic of the patient’s ethnic descent.
Treatment
Gaucher’s disease belongs to a very limited group of genetic diseases that have an effective treatment. Patients can be treated with enzyme replacement therapy, with an enzyme artificially synthesized in a laboratory.
Enzyme replacement therapy helps decrease spleen volume and improve other symptoms, although it is less effective in bone and spinal impairments. This form of therapy also significantly decreased the need for splenectomy that was more common in the past.
