New research reports that the difference in severity of Parkinson’s symptoms in patients with Gaucher disease may be due to the difference in the genetic makeup of cells in individuals.
Gaucher disease is a genetic condition that leads to an impaired metabolism due to a mutation in a gene called GBA, which codes for the enzyme glucocerebrosidase. This results in an abnormal structure of that enzyme, leading to abnormalities in specific cells. This, in turn, causes a number of issues such as anemia, bone disease, organomegaly (enlargement of the viscera), and thrombocytopenia (when blood has fewer platelets than normal).
These symptoms lead to an inflammatory response from the body, which is one of the major problems in Gaucher patients.
Gaucher disease is stratified into several classes, with Gaucher type 1 (GD1) being the mildest subtype. About 4 percent of patients with GD1 develop Parkinson’s disease. Even if patients with GD1 don’t meet all the criteria to be diagnosed with Parkinson’s disease, more than 21 percent of GD1 patients demonstrate at least one parkinsonian symptom.
Mutations in the GBA gene have been found to be correlated with an increased risk of Parkinson’s disease, but the processes by which GBA mutations cause Parkinson’s have not been clear.
While patients with different mutations would not have different clinical treatments for Parkinson’s, classifying the different mutations and their subsequent risk for Parkinson’s disease can lead to helpful genetic counseling.
Researchers are currently unable to determine which Gaucher disease patients will develop Parkinson’s, but they believe it may have to do with the different types of GBA mutations that Gaucher patients inherit.
It’s widely known that patients with milder Gaucher symptoms develop Parkinson’s disease. Researchers suggest this might be due to Parkinson’s being a more benign manifestation of Gaucher disease, while patients with more severe mutations do not live long enough to develop Parkinson’s.
Researchers at the University of Cincinnati reported two case studies of patients with GD1 who developed Parkinson’s disease at different stages in an effort to understand what causes the difference between severity and timing of Parkinson’s development in Gaucher patients.
The two patients both demonstrated early-onset Parkinson’s disease. However, one was diagnosed with GD1 in infancy while the other was diagnosed in adulthood. The patient with the earlier diagnosis of GD1 has the N370S homozygous mutation (an identical mutation in both copies of the parent’s genes), which is a milder GD1 mutation. The patient with the later-onset diagnosis is heterozygous — a mutation in one copy of the gene, in this case in L44P — a more severe mutation.
One study, published in the journal Neurology, found that patients with severe GD1 mutations have a 13.6-fold increased risk of Parkinson’s disease development, while patients with mild mutations have a 2.2-fold increased risk.
Also, patients with severe mutations have an average earlier age of onset of 55.7 years, compared to patients with mild mutations, at 57.9 years.
This study highlights the overlap with GD1 mutations. Researchers said that additional research is needed to determine the different contributions of GBA mutations to the development of Parkinson’s disease.