Evidence for Cholinergic Dysfunction in Autosomal Dominant Kufs Disease

Authors

Pamela JarrettFollow
Alexander Easton
Kenneth Rockwood
Sarah Dyack
Alexander McCollum
Victoria Siu, London Health Science CentreFollow
Seyed M Mirsattari, Western UniversityFollow
Andreu Massot-Tarrús, London Health Science Centre
M Jill Beis
Nolan D'Souza, London Health Science Centre
Sultan Darvesh

Document Type

Article

Publication Date

12-10-2017

Journal

The Canadian Journal of Neurological Sciences / Le Journal Canadien des Sciences Neurologiques

Volume

45

Issue

2

First Page

150

Last Page

157

URL with Digital Object Identifier

https://doi.org/10.1017/cjn.2017.261

Abstract

Objective

Neuronal ceroid-lipofuscinoses are a heterogeneous group of inherited disorders in which abnormal lipopigments form lysosomal inclusion bodies in neurons. Kufs disease is rare, and clinical symptoms include seizures, progressive cognitive impairment, and myoclonus. Most cases of Kufs disease are autosomal recessive; however, there have been a few case reports of an autosomal dominant form linked to mutations within the DNAJC5 gene.

Methods

We describe a family with Kufs disease in which the proband and three of her four children presented with cognitive impairment, seizures, and myoclonus.

Results

Genetic testing of all four children was positive for a c.346_348delCTC(p.L116del) mutation in the DNAJC5 gene. The proband brain had an abundance of neuronal lipofuscin in the cerebral cortex, striatum, amygdala, hippocampus, substantia nigra, and cerebellum. There were no amyloid plaques or neurofibrillary tangles. Immunohistochemistry demonstrated that the cholinergic neurons and cholinergic projection fibers were spared, but there was a profound loss of choline acetyltransferase within the caudate, putamen, and basal forebrain. This suggests a loss of choline acetyltransferase as opposed to a loss of the neurons.

Conclusions

This report describes the clinical history of autosomal dominant Kufs disease, the genetic mutation within the DNAJC5 gene, and the neuropathological findings demonstrating depletion of choline acetyltransferase in the brain.

Notes

Article available at The Canadian Journal of Neurological Sciences / Le Journal Canadien des Sciences Neurologiques, Vol. 45(2).

https://doi.org/10.1017/cjn.2017.261

© 2017 The Canadian Journal of Neurological Sciences, Inc.