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Eur J Neurol. 2017 Jan;24(1):37-45. doi: 10.1111/ene.13125. Epub 2016 Sep 29.

Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation.

Author information

1
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
2
Department of Neurology, Niigata University, Niigata, Japan.
3
Department of Brain Disease Research, Shinshu University School of Medicine, Matsumoto, Japan.
4
Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
5
Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
6
Department of Medical Technology, School of Health Sciences Faculty of Medicine, Niigata University, Niigata, Japan.
7
Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan.
8
Department of Molecular Neuroscience, Niigata University, Niigata, Japan.
9
Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.

Abstract

BACKGROUND AND PURPOSE:

The clinical characteristics of colony stimulating factor 1 receptor (CSF1R) related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) have been only partially elucidated.

METHODS:

Clinical data from CSF1R mutation carriers who had been seen at our institutions or reported elsewhere were collected and analysed using a specific investigation sheet to standardize the data.

RESULTS:

In all, 122 cases from 90 families with CSF1R mutations were identified. The mean age of onset was 43 years (range 18-78 years), the mean age at death was 53 years (range 23-84 years) and the mean disease duration was 6.8 years (range 1-29 years). Women had a significantly younger age of onset than men (40 vs. 47 years, P = 0.0006, 95% confidence interval 3.158-11.177). There was an age-dependent penetrance that was significantly different between the sexes (P = 0.0013). Motor dysfunctions were the most frequent initial symptom in women whose diseases began in their 20s. Thinning of the corpus callosum, abnormal signalling in pyramidal tracts, diffusion-restricted lesions and calcifications in the white matter were characteristic imaging findings of ALSP. The calcifications were more frequently reported in our case series than in the literature (54% vs. 3%). Seventy-nine per cent of the mutations were located in the distal part of the tyrosine kinase domain of CSF1R (102 cases). There were no apparent phenotype-genotype correlations.

CONCLUSIONS:

The characteristics of ALSP were clarified. The phenotype of ALSP caused by CSF1R mutations is affected by sex.

KEYWORDS:

adult-onset leukoencephalopathy with axonal spheroids and pigmented glia; colony stimulating factor 1 receptor; hereditary diffuse leukoencephalopathy with spheroids; leukoencephalopathy; pigmented orthochromatic leukodystrophy

PMID:
27680516
PMCID:
PMC5215554
DOI:
10.1111/ene.13125
[Indexed for MEDLINE]
Free PMC Article

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