Leukoencephalopathy with vanishing white matter (VWM), also called Childhood ataxia with central hypomyelination (CACH) syndrome. Late-childhood/juvenile-onset form.
Incidence
CACH/VWM is inherited in an autosomal recessive manner. The prevalence is not known, but CACH/VWM is considered one of the most common leukodystrophies. In some countries, its incidence is close to that of metachromatic leukodystrophy.
Clinical Characteristics
Late-childhood/juvenile-onset form. Patients develop symptoms between five and 15 years of age. They often have a more slowly progressive spastic diplegia, relative sparing of cognitive ability, and likely long-term survival with long periods of stability and even improvement of motor function [Schiffmann et al 1994, van der Knaap et al 1998]. However, rapid progression and death after a few months have also been described [van der Knaap et al 1998). Neuropathologic examination. The findings in general are a "cavitating orthochromatic leukodystrophy with rarity of myelin breakdown and relative sparing of axons". Cerebral and cerebellar myelin is markedly diminished, whereas the spinal cord is relatively spared. Vacuolation and cavitation of the white matter are diffuse giving a spongiform appearance. Oligodendrocytes are increased in number. The hallmark is the presence of oligodendrocytes with "foamy" cytoplasm and markedly hypotrophic and sometimes atypical astrocytes.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
The diagnosis of childhood ataxia with central nervous system hypomyelination/leukoencephalopathy with vanishing white matter (CACH/VWM) can be made with confidence in patients with typical clinical findings, characteristic abnormalities on cranial MRI, and identifiable mutations in one of the five causative genes. Routine laboratory tests, including spinal fluid analysis, are normal.The diagnosis of CACH/VWM can be made with confidence in patients with typical clinical findings, characteristic abnormalities on cranial MRI, and identifiable mutations in one of five causative genes ( EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5) encoding the five subunits of the eucaryotic translation initiation factor, eIF2B. Mutations have been found in more than 95% of patients, using sequence analysis or mutation scanning.