Megalencephalic leukoencephalopathy with subcortical cysts: chronic white matter oedema due to a defect in brain ion and water homoeostasis.
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is characterised by chronic white matter oedema. The disease has an infantile onset and leads to slow neurological deterioration in most cases, but, surprisingly, some patients recover. The first disease gene, MLC1, identified in 2001, is mutated in 75% of patients. At that time, nothing was known about MLC1 protein function and the pathophysiology of MLC. More recently, HEPACAM (also called GLIALCAM) has been identified as a second disease gene. GlialCAM serves as an escort for MLC1 and the chloride channel CLC2. The defect in MLC1 has been shown to hamper the cell volume regulation of astrocytes. One of the most important consequences involves the potassium siphoning process, which is essential in brain ion and water homoeostasis. An understanding of the mechanisms of white matter oedema in MLC is emerging. Further insight into the specific function of MLC1 is necessary to find treatment targets.
Department of Pediatrics/Child Neurology, VU University Medical Centre, Amsterdam, Netherlands. ms.vanderknaap@vumc.nl
Marjo S
MS
van der Knaap
Ilja
I
Boor
Raúl
R
Estévez
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D001929:Brain Edema / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D018797:Cell Cycle Proteins; D002908:Chronic Disease; D003560:Cysts / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D056784:Leukoencephalopathies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008565:Membrane Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D014867:Water / Q000502:physiology
D018797:Cell Cycle Proteins; C487620:HEPACAM protein, human; D007473:Ion Channels; C425069:MLC1 protein, human; D008565:Membrane Proteins; D011506:Proteins; D014867:Water