A new leucoencephalopathy, the CACH (Childhood Ataxia with Central Nervous System Hypomyelination) or Vanishing White Matter (VWM) syndrome was identified on clinical and MRI criteria. Typical forms are characterized by: 1) an onset between 2 and 5 years of age with a cerebello-spastic syndrome exacerbated by episodes of fever or head trauma leading to death after 5 to 10 years; 2) a diffuse involvement of the white matter on MRI with replacement by CSF-like signal intensity (cavitation); 3) a recessive autosomal mode of inheritance; 4) neuropathological findings consistent with a cavitating orthochromatic leucodystrophy with an increased number of oligodendrocytes some of which appear “foamy”. So far a total of 148 cases has been reported.
This disease is linked to mutations in the 5 EIF2B genes encoding the 5 subunits involved in the eukaryotic initiation of factor 2B (elF2B) associated with protein synthesis and its regulation under conditions of cellular stress. Clinical symptoms are variable, from fatal infantile forms (Cree leucoencephalopathy) and congenital forms associated with extra-neurological disturbances to juvenile and adult forms (ovario-leucodystophy) characterized by cognitive and behavioural dysfunction and slow progression. These disorders have therefore been called the elF2B-related leucoencephalopathies. The prevalence of these diseases remains unknown.
The diagnosis rests on the detection of EIF2B mutations predominantly in the EIF2B5 gene. A lowering of intrinsic elF2B factor activity (involved in guanine exchange) in lymphoblasts seems to have diagnostic value. The pathophysiology includes a deficiency in astrocyte maturation leading to an increased susceptibility of cells to stress in white matter.
There is no specific treatment available except for the “prevention of cellular stress”. Corticosteroids have sometimes been beneficial in the acute phases. Prognosis seems to be correlated with age at onset, the earlier forms being more severe.
© 2007 Elsevier Masson SAS. Tous droits réservés.