Epidemiological Study to Determine Mutations in the Gaucher Gene in Patients With Idiopathic Parkinson's Disease for Phenotype-genotype Correlation

Parkinson's disease (also known as Parkinson's, Parkinson disease, or PD) is a degenerative disorder of the central nervous system that impairs motor skills, cognitive processes, and other functions. The most obvious symptoms are motor-related, including tremor, rigidity, slowness of movement, and postural instability. Among non-motor symptoms are autonomic dysfunction and sensory and sleep difficulties. Cognitive and neurobehavioral problems, including dementia, are common in the advanced stages of the disease. PD usually appears around the age of 60, although there are young-onset cases.

Gaucher's disease is a genetic disease in which a fatty substance (lipid) accumulates in cells and certain organs. Gaucher's disease is the most common of the lysosomal storage diseases. It is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as acid β-glucosidase). The enzyme acts on a fatty substance glucocerebroside (also known as glucosylceramide). When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells (mononuclear leukocytes). Glucocerebroside can collect in the spleen, liver, kidneys, lungs, brain and bone marrow.

Symptoms of Parkinson's syndrome in classical type 1 Gaucher patients were first systematically described in 1996. In GD patients, a marked heterogeneity is detected in terms of disease-causing mutations. In 17 Gaucher patients with symptoms of Parkinson's disease, 12 different genotypes were sequenced and compared to other Parkinson's patients, a lower L-dopa responsiveness, a higher frequency of cortical dysfunction and a relatively early onset of the symptoms was described. Many of these Gaucher patients with clinical Parkinson's symptoms had a positive family history of Parkinson's disease among relatives with heterozygous mutations in the Gaucher gene that could be confirmed in systematic studies.