title: Late-Onset Metachromatic Leukodystrophy with Early Onset Dementia Associated with a Novel Missense Mutation in the Arylsulfatase A Gene.
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.
authors.affiliation: Department of Neurology, University Medical Center Göttingen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Stoeck
authors.affiliation: Department of Neuroradiology, University Medical Center Göttingen, Germany.
authors.forename: Marios Nikos
authors.initials: MN
authors.lastname: Psychogios
authors.affiliation: Department of Neuropaediatrics, University Medical Center Göttingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ohlenbusch
authors.affiliation: Department of Neuropaediatrics, University Medical Center Göttingen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Steinfeld
authors.affiliation: Department of Neurology, University Medical Center Göttingen, Germany.|Department of Neuroimmunology, Institute for Multiple Sclerosis Research and Hertie Foundation, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Schmidt
mesh_terms: D017668:Age of Onset; D001921:Brain / Q000000981:diagnostic imaging*; D002553:Cerebroside-Sulfatase / Q000235:genetics*; D004252:DNA Mutational Analysis; D003704:Dementia / Q000000981:diagnostic imaging / Q000235:genetics*; D003937:Diagnosis, Differential; D005091:Exons; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009483:Neuropsychological Tests
chemical_list: D002553:Cerebroside-Sulfatase
keywords: Arylsulfatase A; early onset dementia; genetic testing; late-onset metachromatic leukodystrophy