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

T. Konno, K. Yoshida, T. Mizuno, T. Kawarai, M. Tada, H. Nozaki, S. I. Ikeda, M. Nishizawa, O. Onodera, Zbigniew K Wszolek, T. Ikeuchi

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)37-45
Number of pages9
JournalEuropean Journal of Neurology
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2017

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Colony-Stimulating Factor Receptors
Leukoencephalopathies
Macrophage Colony-Stimulating Factor
Neuroglia
Mutation
Age of Onset
Pyramidal Tracts
Penetrance
Corpus Callosum
Protein-Tyrosine Kinases
Confidence Intervals
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation. / Konno, T.; Yoshida, K.; Mizuno, T.; Kawarai, T.; Tada, M.; Nozaki, H.; Ikeda, S. I.; Nishizawa, M.; Onodera, O.; Wszolek, Zbigniew K; Ikeuchi, T.

In: European Journal of Neurology, Vol. 24, No. 1, 01.01.2017, p. 37-45.

Research output: Contribution to journalArticle

Konno, T, Yoshida, K, Mizuno, T, Kawarai, T, Tada, M, Nozaki, H, Ikeda, SI, Nishizawa, M, Onodera, O, Wszolek, ZK & Ikeuchi, T 2017, 'Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation', European Journal of Neurology, vol. 24, no. 1, pp. 37-45. https://doi.org/10.1111/ene.13125
Konno, T. ; Yoshida, K. ; Mizuno, T. ; Kawarai, T. ; Tada, M. ; Nozaki, H. ; Ikeda, S. I. ; Nishizawa, M. ; Onodera, O. ; Wszolek, Zbigniew K ; Ikeuchi, T. / Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation. In: European Journal of Neurology. 2017 ; Vol. 24, No. 1. pp. 37-45.
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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.",
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AU - Konno, T.

AU - Yoshida, K.

AU - Mizuno, T.

AU - Kawarai, T.

AU - Tada, M.

AU - Nozaki, H.

AU - Ikeda, S. I.

AU - Nishizawa, M.

AU - Onodera, O.

AU - Wszolek, Zbigniew K

AU - Ikeuchi, T.

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N2 - 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.

AB - 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.

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KW - hereditary diffuse leukoencephalopathy with spheroids

KW - leukoencephalopathy

KW - pigmented orthochromatic leukodystrophy

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