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Alpha‐mannosidosis: characterization of CNS pathology and correlation between CNS pathology and cognitive function
Author(s) -
Borgwardt L.,
Danielsen E.R.,
Thomsen C.,
Månsson J.E.,
Taouatas N.,
Thuesen A.M.,
Olsen K.J.,
Fogh J.,
Dali C.I.,
Lund A.M.
Publication year - 2016
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12642
Subject(s) - pathology , gliosis , cerebrospinal fluid , white matter , central nervous system , glial fibrillary acidic protein , magnetic resonance imaging , medicine , neurodegeneration , endocrinology , immunohistochemistry , disease , radiology
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.