Last modified: 2014-04-03
Abstract
Introduction: VWM is an autosomal recessive hereditary leukodystrophy, linked to mutations in genes encoding the eukaryotic initiation factor 2B (eIF2B). Neurological features and clinical phenotypes are variable. The most common variant has a childhood onset and characteristic abnormalities on cranial MRI. Methods: Retrospective and prospective study: clinical, neuroimaging and genetic analysis. Patients were divided in groups according to age at onset: Group 1 (<2 years), group 2 (age 2-5) and group 3 (age >5), and according to disability scores (1=gait disturbance to 5=deceased). Results: 10 patients (7male/3female), 3 siblings. 9/10 had prior normal development. Average age at onset was 7 (1-13years), with gait disturbance (6/10), development regression (3/10) and tremor (1/10). History of cranial concussion (4/10) and febrile infection (1/10). Group distribution: 1 (n=2), 2 (n=1), 3 (n=7). Disability score distribution: 1 (n=6), 2 (n=1), 4 (n=2), 5 (n=1). Phenotypes: late childhood/early childhood onset (7/3). Symptoms: spasticity (7/10), cerebellar ataxia (7/10). Clinical monitoring: 3-12 years, rapidly progressive (n=6), progressive (n=2), fulminant (1) evolution. Brain MRI: diffuse, symmetrical abnormal white matter signal (10/10), most with cystic degeneration. Genetic study (9/10): IF2B5-R113H mutation (homozygous/heterozygous=2/6), IF2B4-R373C homozygous (1). Conclusion/Discussion: VWM is one of the most prevalent inherited childhood leucoencephalopathies, therefore it must be considered in the differential diagnosis. In this series the classical form was the most frequent, with characteristic white matter abnormalities in MRI, and most with IF2B5- R113H mutation.