German-Canadian family (family A) with parkinsonism, amyotrophy, and dementia — Longitudinal observations

• Published in: Parkinsonism & related disorders 1997-11, Vol.3 (3), p.125-139
• Main Authors: Wszolek, Z.K., Vieregge, P., Uitti, R.J., Gasser, T., Yasuhara, O., Mcgeer, P., Berry, K., Calne, D.B., Vingerhoets, F.J.G., Klein, C., Pfeiffer, R.F.
• Format: Article
• Language: English
• Subjects: Amyotrophy; Dementia; Genealogic; Genetic; Parkinsonism; Positron emission tomography studies; Postmortem
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/S1353-8020(97)00013-8

Etiology of Parkinson's disease (PD), amyotrophy lateral sclerosis (ALS), and Alzheimer's disease (AD) remains uncertain. Environmental factors probably play a role, but genetic influences may predispose certain individuals to develop each of these major neurodegenerative disorders. We describe our longitudinal observations concerning a Canadian family traced to Northern Germany. Autosornal dominant inheritance has been established. Affected members present with L-dopa responsive parkinsonism and amyotrophy. In the German portion of the family some individuals displayed only dementia or focal dystonia. Linkage analysis studies performed with polymorphic markers associated with 13 candidate genes provided no significant evidence for linkage with any of the genes examined. Positron emission tomography with [ 18F]-6-fluoro-L-dopa (FD) and [su11C]-raclopride (raclopride) of one affected subject revealed reduced striatal FD uptake particularly in putamen, and an increased raclopride striatum/background ratio. Postmortem levels of dopamine and its metabolites were greatly reduced in caudate and putamen of two patients. There was substantial neuronal loss in the substantia nigra and the presence of abundant eosinophilic granules (different than Lewy bodies) in surviving neurons. One of them also showed mild loss of anterior horn cells, while another showed abundant senile plaques and some neurofibrillary tangles in distribution and intensity typical of mild to moderate AD. Our report further describes this unique family with a combination of clinical features of PD, ALS, and AD. By studying kindreds like this we may learn more about the pathophysiology of sporadic forms of PD, ALS, or even AD.