Research News from Ellen Sidransky

Researchers from the National Institute of Mental Health and the National Human Genome Research Institute in a team led by Ellen Sidransky M.D., have discovered an association between the degenerative neurological disorder, Parkinson disease, and Gaucher disease, a recessively inherited metabolic disorder. Gaucher disease is caused by mutations in the gene for the enzyme glucocerebrosidase and results in the accumulation of harmful quantities of a substance, glucocerebroside, in patients’ cells.

While mutations in the glucocerebrosidase gene (GBA) are rare in the general population, their study, published in the January 2004 issue of Molecular Genetics and Metabolism, showed that GBA mutations were found in brain samples of subjects with Parkinson disease more frequently than expected. Five American repositories supplied autopsy brain samples from 57 individuals with pathologically confirmed parkinsonism and from 44 controls, the GBA gene was investigated in these samples. Alterations were identified in 14% of the samples, more frequently than mutations in other known Parkinson disease genes. These findings suggested that carrying a GBA mutation may be a risk factor for the development of parkinsonism.

The results obtained from brain samples have recently been substantiated in blood samples from three different patient groups. A group in Israel screened 100 Ashkenazi Jewish patients from a Parkinson disease clinic in Northern Israel and identified GBA mutations in 31%. Two other groups, from New York and Toronto, found GBA mutations in their patients with Parkinson disease at a rate of 11% and 5.6%, respectively. A fourth study documented that in several families of patients with Gaucher disease, there were more close relatives suffering from parkinsonism than expected. It is important to note, however, that most Gaucher patients and carriers do not develop Parkinson disease, and mutations in glucocerebrosidase may be one of many risk factors leading to parkinsonism.

The identification of GBA mutations in patients with Parkinson disease from different countries supports the theory of a role for glucocerebrosidase in the development of parkinsonism. Having access to brain bank samples is incredibly important, because detailed pathology studies of autopsy samples can confirm and clarify clinical diagnoses, and allow more accurate comparisons between different patient populations. The contributions of donors to brain banks in Britain and other countries will help develop a better understanding of the connection between Gaucher disease and parkinsonism.