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



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.



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.



The characteristics of ALSP were clarified. The phenotype of ALSP caused by CSF1R mutations is affected by sex.
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.|Department of Neurology, Niigata University, Niigata, Japan.
T
T
Konno
Department of Brain Disease Research, Shinshu University School of Medicine, Matsumoto, Japan.
K
K
Yoshida
Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
T
T
Mizuno
Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
T
T
Kawarai
Department of Neurology, Niigata University, Niigata, Japan.
M
M
Tada
Department of Medical Technology, School of Health Sciences Faculty of Medicine, Niigata University, Niigata, Japan.
H
H
Nozaki
Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan.
S-I
SI
Ikeda
Department of Neurology, Niigata University, Niigata, Japan.
M
M
Nishizawa
Department of Molecular Neuroscience, Niigata University, Niigata, Japan.
O
O
Onodera
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Z K
ZK
Wszolek
Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
T
T
Ikeuchi
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001369:Axons / Q000473:pathology; D003337:Corpus Callosum / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006579:Heterozygote; D006801:Humans; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000209:etiology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D009457:Neuroglia / Q000473:pathology; D019683:Penetrance; D011712:Pyramidal Tracts / Q000000981:diagnostic imaging / Q000473:pathology; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D012727:Sex Characteristics; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology; D055815:Young Adult; D016186:Receptor, Macrophage Colony-Stimulating Factor
D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; C000622186:CSF1R protein, human; D016186:Receptor, Macrophage Colony-Stimulating Factor
adult-onset leukoencephalopathy with axonal spheroids and pigmented glia; colony stimulating factor 1 receptor; hereditary diffuse leukoencephalopathy with spheroids; leukoencephalopathy; pigmented orthochromatic leukodystrophy
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