Late-Onset Metachromatic Leukodystrophy with Early Onset Dementia Associated with a Novel Missense Mutation in the Arylsulfatase A Gene

Article type: Research Article

Authors: Stoeck, Katharina^a | Psychogios, Marios Nikos^b | Ohlenbusch, Andreas^c | Steinfeld, Robert^c | Schmidt, Jens^{a; d; *}

Affiliations: [a] Department of Neurology, University Medical Center Göttingen, Germany | [b] Department of Neuroradiology, University Medical Center Göttingen, Germany | [c] Department of Neuropaediatrics, University Medical Center Göttingen, Germany | [d] Department of Neuroimmunology, Institute for Multiple Sclerosis Research and Hertie Foundation, University Medical Center Göttingen, Göttingen, Germany

Correspondence: [*] Correspondence to: Prof. Jens Schmidt, MD, Department of Neurology, University Medical Center Göttingen, Robert-Koch-Str.40, 37075 Göttingen, Germany. Tel.: +49 551 3922355; Fax: +49 551 398405; E-mail: j.schmidt@gmx.org.

Abstract: A 48-year-old male patient presented with personality changes and progressive memory loss over 2 years with initially suspected Hashimoto’s encephalopathy. Strategy of diagnostic workup of early onset dementia included dementia from neurodegenerative, neuroinflammatory, metabolic/toxic, and psychiatric origin. The patient’s neurological exam was normal. MRI revealed a leukencephalopathy, predominantly in the frontal periventricular white matter, without notable changes over 2 years. On neurophysiological examination, prolonged central conduction times and a sensorimotor polyneuropathy were noted. Neuropsychological impairment included disorientation in place and a reduced short time memory. Behavioral alterations were predominated by sudden mood changes and disinhibition. Cerebrospinal fluid was normal. Despite presence of thyroid autoantibodies, glucocorticosteroid treatment did not improve the dementia. A metachromatic leukodystrophy was diagnosed by decreased arylsulfatase-A activity in leucocytes/fibroblasts and identification of a compound heterozygous mutation in the ARSA gene: c.542T>G (exon 3) and the novel mutation c.1013T>C (exon 6). Pathogenic function was suggested by bioinformatic mutation search. In a patient with early onset dementia, strategic diagnostic workup including genetic assessment revealed an adult-onset metachromatic leukodystrophy with a novel mutation in the arylsulfatase A gene.

Keywords: Arylsulfatase A, early onset dementia, genetic testing, late-onset metachromatic leukodystrophy

DOI: 10.3233/JAD-150819

Journal: Journal of Alzheimer's Disease, vol. 51, no. 3, pp. 683-687, 2016