Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Alpha-mannosidosis: characterization of CNS pathology and correlation between CNS pathology and cognitive function

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Mosaic MECP2 variants in males with classical Rett syndrome features, including stereotypical hand movements

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Leucocytes Mutation load Declines with Age in Carriers of the m.3243A>G Mutation. A 10-year Prospective Cohort

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Targeted Gene Sequencing and Whole-Exome Sequencing in Autopsied Fetuses with Prenatally Diagnosed Kidney Anomalies

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Dynamic soft tissue changes in the orbit after a blowout fracture

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Age-related renal function decline in Fabry disease patients on enzyme replacement therapy: a longitudinal cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Impaired Fat Oxidation During Exercise in Long-Chain Acyl-CoA Dehydrogenase Deficiency Patients and Effect of IV-Glucose

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Relationship between muscle inflammation and fat replacement assessed by MRI in facioscapulohumeral muscular dystrophy

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Alpha-mannosidosis (AM) (OMIM 248500) is a rare lysosomal storage disease. The understanding of the central nervous system (CNS) pathology is limited. This study is the first describing the CNS pathology and the correlation between the CNS pathology and intellectual disabilities in human AM. Thirty-four patients, aged 6-35 years, with AM were included. Data from 13 healthy controls were included in the analysis of the magnetic resonance spectroscopy (MRS). Measurements of CNS neurodegeneration biomarkers in cerebrospinal fluid (CSF), CSF-oligosaccharides, and performance of cerebral magnetic resonance imaging (MRI) and MRS were carried out. On MRI, 5 of 10 patients had occipital white matter (WM) signal abnormalities, and 6 of 10 patients had age-inappropriate myelination. MRS demonstrated significantly elevated mannose complex in gray matter and WM. We found elevated concentrations of tau-protein, glial fibrillary acidic protein and neurofilament light protein in 97 patients, 74% and 41% of CSF samples, respectively. A negative correlation between CSF-biomarkers and cognitive function and CSF-oligosaccharides and cognitive function was found. The combination of MRS/MRI changes, elevated concentrations of CSF-biomarkers and CSF-oligosaccharides suggests gliosis and reduced myelination, as part of the CNS pathology in AM. Our data demonstrate early neuropathological changes, which may be taken into consideration when planning initiation of treatment.

Original languageEnglish
JournalClinical Genetics
Volume89
Issue number4
Pages (from-to)489-494
ISSN0009-9163
DOIs
Publication statusPublished - Apr 2016

ID: 45885015