Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis

C. Sundal, M. Baker, V. Karrenbauer, M. Gustavsen, S. Bedri, A. Glaser, K. M. Myhr, K. Haugarvoll, H. Zetterberg, H. Harbo, I. Kockum, J. Hillert, Zbigniew K Wszolek, Rosa V Rademakers, O. Andersen

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a devastating, hereditary white matter (WM) disorder with heterogeneous neuropsychiatric features. Colony stimulating factor 1 receptor (CSF1R) mutations were looked for in primary progressive multiple sclerosis (PPMS) patients and the clinical features of a family with a novel CSF1R mutation are reported. Methods: CSF1R exons 12-22 in a cohort of 220 PPMS patients from the Swedish and Norwegian national multiple sclerosis registries were sequenced. Results: One patient had a novel mutation, c.2562T>A; p.Asn854Lys, in the CSF1R gene. Her symptoms started at the age of 29 years with insidious onset of pyramidal weakness in the left leg. The cerebrospinal fluid examination showed four intrathecal immunoglobulin G bands. A magnetic resonance imaging scan performed 4 years after symptom onset demonstrated patchy deep WM lesions. She was diagnosed as having PPMS and treated with intramuscular interferon beta 1a. Due to slow disease progression, the development of memory decline and cerebellar signs, she was given subcutaneous interferon beta 1a without any benefit. The updated pedigree indicated that five siblings also had the CSF1R gene mutation; one was diagnosed with PPMS. Six more distant relatives also had a neurological disorder; four were clinically diagnosed with PPMS. Conclusions: Our study indicates that a chronic course of HDLS may mimic PPMS. Genetic testing for CSF1R gene mutations in PPMS cases with a positive family history of neurological disorders may establish the diagnosis of HDLS.

Original languageEnglish (US)
Pages (from-to)328-333
Number of pages6
JournalEuropean Journal of Neurology
Volume22
Issue number2
DOIs
StatePublished - Feb 1 2015

Fingerprint

Chronic Progressive Multiple Sclerosis
Colony-Stimulating Factor Receptors
Macrophage Colony-Stimulating Factor
Phenotype
Mutation
Nervous System Diseases
Genes
Genetic Testing
Pedigree
Hereditary Diffuse Leukoencephalopathy with Spheroids
Multiple Sclerosis
Cerebrospinal Fluid
Registries
Disease Progression
Siblings
Exons
Leg
Immunoglobulin G
Magnetic Resonance Imaging

Keywords

  • Hereditary diffuse leukoencephalopathy with spheroids
  • White matter lesions

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Sundal, C., Baker, M., Karrenbauer, V., Gustavsen, M., Bedri, S., Glaser, A., ... Andersen, O. (2015). Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis. European Journal of Neurology, 22(2), 328-333. https://doi.org/10.1111/ene.12572

Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis. / Sundal, C.; Baker, M.; Karrenbauer, V.; Gustavsen, M.; Bedri, S.; Glaser, A.; Myhr, K. M.; Haugarvoll, K.; Zetterberg, H.; Harbo, H.; Kockum, I.; Hillert, J.; Wszolek, Zbigniew K; Rademakers, Rosa V; Andersen, O.

In: European Journal of Neurology, Vol. 22, No. 2, 01.02.2015, p. 328-333.

Research output: Contribution to journalArticle

Sundal, C, Baker, M, Karrenbauer, V, Gustavsen, M, Bedri, S, Glaser, A, Myhr, KM, Haugarvoll, K, Zetterberg, H, Harbo, H, Kockum, I, Hillert, J, Wszolek, ZK, Rademakers, RV & Andersen, O 2015, 'Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis', European Journal of Neurology, vol. 22, no. 2, pp. 328-333. https://doi.org/10.1111/ene.12572
Sundal, C. ; Baker, M. ; Karrenbauer, V. ; Gustavsen, M. ; Bedri, S. ; Glaser, A. ; Myhr, K. M. ; Haugarvoll, K. ; Zetterberg, H. ; Harbo, H. ; Kockum, I. ; Hillert, J. ; Wszolek, Zbigniew K ; Rademakers, Rosa V ; Andersen, O. / Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis. In: European Journal of Neurology. 2015 ; Vol. 22, No. 2. pp. 328-333.
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abstract = "Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a devastating, hereditary white matter (WM) disorder with heterogeneous neuropsychiatric features. Colony stimulating factor 1 receptor (CSF1R) mutations were looked for in primary progressive multiple sclerosis (PPMS) patients and the clinical features of a family with a novel CSF1R mutation are reported. Methods: CSF1R exons 12-22 in a cohort of 220 PPMS patients from the Swedish and Norwegian national multiple sclerosis registries were sequenced. Results: One patient had a novel mutation, c.2562T>A; p.Asn854Lys, in the CSF1R gene. Her symptoms started at the age of 29 years with insidious onset of pyramidal weakness in the left leg. The cerebrospinal fluid examination showed four intrathecal immunoglobulin G bands. A magnetic resonance imaging scan performed 4 years after symptom onset demonstrated patchy deep WM lesions. She was diagnosed as having PPMS and treated with intramuscular interferon beta 1a. Due to slow disease progression, the development of memory decline and cerebellar signs, she was given subcutaneous interferon beta 1a without any benefit. The updated pedigree indicated that five siblings also had the CSF1R gene mutation; one was diagnosed with PPMS. Six more distant relatives also had a neurological disorder; four were clinically diagnosed with PPMS. Conclusions: Our study indicates that a chronic course of HDLS may mimic PPMS. Genetic testing for CSF1R gene mutations in PPMS cases with a positive family history of neurological disorders may establish the diagnosis of HDLS.",
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AU - Baker, M.

AU - Karrenbauer, V.

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AU - Bedri, S.

AU - Glaser, A.

AU - Myhr, K. M.

AU - Haugarvoll, K.

AU - Zetterberg, H.

AU - Harbo, H.

AU - Kockum, I.

AU - Hillert, J.

AU - Wszolek, Zbigniew K

AU - Rademakers, Rosa V

AU - Andersen, O.

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AB - Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a devastating, hereditary white matter (WM) disorder with heterogeneous neuropsychiatric features. Colony stimulating factor 1 receptor (CSF1R) mutations were looked for in primary progressive multiple sclerosis (PPMS) patients and the clinical features of a family with a novel CSF1R mutation are reported. Methods: CSF1R exons 12-22 in a cohort of 220 PPMS patients from the Swedish and Norwegian national multiple sclerosis registries were sequenced. Results: One patient had a novel mutation, c.2562T>A; p.Asn854Lys, in the CSF1R gene. Her symptoms started at the age of 29 years with insidious onset of pyramidal weakness in the left leg. The cerebrospinal fluid examination showed four intrathecal immunoglobulin G bands. A magnetic resonance imaging scan performed 4 years after symptom onset demonstrated patchy deep WM lesions. She was diagnosed as having PPMS and treated with intramuscular interferon beta 1a. Due to slow disease progression, the development of memory decline and cerebellar signs, she was given subcutaneous interferon beta 1a without any benefit. The updated pedigree indicated that five siblings also had the CSF1R gene mutation; one was diagnosed with PPMS. Six more distant relatives also had a neurological disorder; four were clinically diagnosed with PPMS. Conclusions: Our study indicates that a chronic course of HDLS may mimic PPMS. Genetic testing for CSF1R gene mutations in PPMS cases with a positive family history of neurological disorders may establish the diagnosis of HDLS.

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