Ivan Fernández-Vega1,2, Katti Pérez de Heredia-Goñi2, Jorge Santos-Juanes3, Miguel Goñi Imizcoz4, Laura Zaldumbide5, Juan Jose Zarranz6, Isidro Ferrer7. 1. Pathology Department of Hospital Universitario Araba, Álava, Spain. 2. Brain Bank Hospital Universitario Araba, Biobanco Vasco para la Investigación (O+eHun), Vitoria, Spain. 3. Pathology Department, Hospital Universitario Central de Asturias, Asturias, Spain. 4. Neurology Department, Hospital Divino Vallés, Burgos, Spain. 5. Pathology Department of Hospital Universitario de Cruces, Bizkaia, Spain. 6. Neurology Department, Hospital Universitario de Cruces, Bizkaia, Spain. 7. Institute of Neuropathology, Bellvitge University Hospital, University of Barcelona, Barcelona, Spain.
Abstract
AIMS: Adult-onset orthochromatic leucodystrophy, associated with pigmented macrophages and hereditary diffuse leucoencephalopathy with spheroids, are two disorders with similar clinical manifestations, radiological characteristics and neuropathological findings. Mutations in the colony-stimulating factor 1 receptor (CSF1R) gene are the hallmark of this spectrum of disease. Furthermore, polycystic membranous lipomembranous osteodysplasia with sclerosing leucoencephalopathy is caused by mutations in two genes, DAP12 and TREM2, which encode proteins involved in the same pathways as CSF1R. We describe a case of sporadic adult-onset orthochromatic leucodystrophy associated with pigmented macrophages diagnosed by biopsy without harbouring mutations in the known targeted genes. METHODS AND RESULTS: A 51-year-old woman, with no familial history of neurological diseases, developed a progressive neurological deterioration showing inappropriate behaviour, ataxia, spasticity, axial dystonia and agitation. Radiological images and a stereotaxic biopsy were conclusive with adult-onset orthochromatic leucodystrophy associated with pigmented macrophages. Genetic analysis did not show mutations in either CSF1R, DAP12 or TREM2. CONCLUSIONS: We add support to the idea that all these entities are closely related diseases linked to a convergent metabolic pathway, but caused by different genes or perhaps by the combination of individually non-pathogenic variations of selected genes. Genetic defects are still barely known in a substantial number of adult leucodystrophies.
AIMS: Adult-onset orthochromatic leucodystrophy, associated with pigmented macrophages and hereditary diffuse leucoencephalopathy with spheroids, are two disorders with similar clinical manifestations, radiological characteristics and neuropathological findings. Mutations in the colony-stimulating factor 1 receptor (CSF1R) gene are the hallmark of this spectrum of disease. Furthermore, polycystic membranous lipomembranous osteodysplasia with sclerosing leucoencephalopathy is caused by mutations in two genes, DAP12 and TREM2, which encode proteins involved in the same pathways as CSF1R. We describe a case of sporadic adult-onset orthochromatic leucodystrophy associated with pigmented macrophages diagnosed by biopsy without harbouring mutations in the known targeted genes. METHODS AND RESULTS: A 51-year-old woman, with no familial history of neurological diseases, developed a progressive neurological deterioration showing inappropriate behaviour, ataxia, spasticity, axial dystonia and agitation. Radiological images and a stereotaxic biopsy were conclusive with adult-onset orthochromatic leucodystrophy associated with pigmented macrophages. Genetic analysis did not show mutations in either CSF1R, DAP12 or TREM2. CONCLUSIONS: We add support to the idea that all these entities are closely related diseases linked to a convergent metabolic pathway, but caused by different genes or perhaps by the combination of individually non-pathogenic variations of selected genes. Genetic defects are still barely known in a substantial number of adult leucodystrophies.
Authors: Spyros Papapetropoulos; Angela Pontius; Elizabeth Finger; Virginija Karrenbauer; David S Lynch; Matthew Brennan; Samantha Zappia; Wolfgang Koehler; Ludger Schoels; Stefanie N Hayer; Takuya Konno; Takeshi Ikeuchi; Troy Lund; Jennifer Orthmann-Murphy; Florian Eichler; Zbigniew K Wszolek Journal: Front Neurol Date: 2022-02-03 Impact factor: 4.003