Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis.
BACKGROUND AND PURPOSE
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.
['Sundal|Christina|C|', 'Baker|Matt|M|', 'Karrenbauer|Virginija|V|', 'Gustavsen|Marte|M|', 'Bedri|Sahl|S|', 'Glaser|Anna|A|', 'Myhr|Kjell-Morten|KM|', 'Haugarvoll|Kristoffer|K|', 'Zetterberg|Henrik|H|', 'Harbo|Hanne|H|', 'Kockum|Ingrid|I|', 'Hillert|Jan|J|', 'Wszolek|Zbigniew|Z|', 'Rademakers|Rosa|R|', 'Andersen|Oluf|O|']
D000328:Adult D005091:Exons D005260:Female D006801:Humans D056784:Leukoencephalopathies D020528:Multiple Sclerosis, Chronic Progressive D009154:Mutation D009664:Norway D010375:Pedigree D010641:Phenotype D016186:Receptor, Macrophage Colony-Stimulating Factor D012042:Registries D035781:Siblings D013548:Sweden
hereditary diffuse leukoencephalopathy with spheroids white matter lesions