Leukodystrophies in Patients with Adult-Onset Ataxia: Frequency and Phenotype (P05.020)

Abstract

Objective: We aimed to determine the frequency of leukodystrophies and its phenotypic spectrum in patients with ataxia of unknown cause. Background A broad spectrum of heterogeneous neurological disorders including lysosomal storage disorders present with chronic progressive cerebellar ataxia. Identifying the underlying etiology is important as it sometimes allows for initiation of pharmacological treatment. Design/Methods: We prospectively studied 107 index patients who presented with adult-onset cerebellar ataxia consistent with autosomal recessive inheritance. Patients were screened for lysosomal enzyme deficiencies including metachromatic leukodystrophy, GM1-Gangliosidosis, Tay-Sachs and Sandhoff9 disease, and Krabbe disease. If clinical evidence was suggestive of other types of leukodystrophies, additional genetic or metabolic testing was performed. Clinical characterization included neurological and psychiatric features and MR-imaging. Results: Screening for lysosomal disorders detected one patient with late-onset Tay Sachs disease and one with metachromatic leukodystrophy. Both patients presented with cognitive deficits and psychiatric comorbidity beside ataxia. Additonal tests revealed two patients with Nieman Pick disease type C, one with cerebrotendinous xanthomatosis, and one with leukencephalopathy with brain stem and spinal cord involvement and lactate elevation. All of them presented with additional signs like cognitive dysfunction, pyramidal affection and/or peripheral neuropathy. Conclusions: Leukodystrophies were responsible for 6% of cryptic ataxia in our series. The concomitant occurrence of cerebellar ataxia with cognitive dysfunction, psychiatric comorbidities, spasticity and/or neuropathy should prompt screening for lysosomal storage disorders. Hyperintensity of cerebral white matter on MR FLAIR images is not an obligate marker in adult-onset leukodystrophies. Supported by: German Ministry of Research and Education (BMBF) grant 01GM0838. Disclosure: Dr. Muller vom Hagen has nothing to disclose. Dr. Synofzik has received personal compensation for activities with Volkswagen Foundation, the Movement Disorder Society, and Fresenius Kabi. Dr. Schicks has nothing to disclose. Dr. Krageloh-Mann has nothing to disclose. Dr. Schoels has received research support from Deutsche Forschungsgemeinschaft, German Research Council, Leukonet, mitoNET, EUROSPA, RISCA, and the HSP-Selbsthilfegruppe Deutschland eV.