Childhood ataxia with central nervous system hypomyelination

Introduction
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By Raphael Schiffmann MD

Childhood ataxia with central nervous system hypomyelination is also known as or subsumes Vanishing white matter disease. -ed.

Mutations affecting the eukaryotic initiation factor 2B (eIF2B) cause one of the most common leukodystrophies, the autosomal recessive childhood ataxia with central nervous system hypomyelination (CACH), or vanishing white matter disease (VWM). Patients may develop a wide spectrum of neurologic abnormalities, from prenatal-onset white matter disease to juvenile- or adult-onset ataxia and dementia, sometimes with ovarian insufficiency. The pattern of diffuse white matter abnormalities on brain MRI and diffusion studies is often diagnostic. A knock-in mouse model of CACH/VWM, which shows a developmental white matter abnormality, is a promising new tool for the research of this devastating disease. Novel promising approaches for specific therapy are being developed. Symptomatic treatment such as deep brain stimulation may alleviate tremor.

Key points

  • Childhood ataxia with CNS hypomyelination (or vanishing white matter disease) is a relatively common leukodystrophy in which most of the patients have a pathognomonic pattern of MRI and diffusion tensor imaging abnormalities.
  • Patients with childhood ataxia with CNS hypomyelination have a usual susceptibility to mild head trauma, fever, and other stresses.
  • Childhood ataxia with CNS hypomyelination can present at ages from the newborn period to mature adulthood.
  • The dysfunction of eIF2B in childhood ataxia with CNS hypomyelination indicates that regulation of protein translation is central to the development and maintenance of brain glial cells.
  • Current treatment is symptomatic, with possible response of cerebellar tremor to deep brain stimulation.

In This Article

Introduction
Historical note and nomenclature
Clinical manifestations
Clinical vignette
Etiology
Pathogenesis and pathophysiology
Epidemiology
Prevention
Differential diagnosis
Diagnostic workup
Prognosis and complications
Management
Pregnancy
Anesthesia
References cited
Contributors