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: Katharina Stoeck, Marios Nikos Psychogios, Andreas Ohlenbusch, Robert Steinfeld, Jens Schmidt
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 51 Issue 3 Pg. 683-7 ( 2016) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 26890752 (Publication Type: Case Reports, Journal Article)

Chemical References

• Cerebroside-Sulfatase

Topics

• Age of Onset
• Brain (diagnostic imaging)
• Cerebroside-Sulfatase (genetics)
• DNA Mutational Analysis
• Dementia (diagnostic imaging, genetics)
• Diagnosis, Differential
• Exons
• Humans
• Leukodystrophy, Metachromatic (diagnostic imaging, genetics)
• Male
• Middle Aged
• Mutation, Missense
• Neuropsychological Tests