Childhood ataxia with central nervous system hypomyelination

Raphael Schiffmann MD (Dr. Schiffmann, Director of the Institute of Metabolic Disease at Baylor Research Institute, received research grants from Amicus Therapeutics, Protalix Biotherapeutics, and Shire.)
Originally released October 27, 1999; last updated November 19, 2016; expires November 19, 2019

This article includes discussion of childhood ataxia with central nervous system hypomyelination, CACH, myelinopathia centralis diffusa, and vanishing white matter disease,. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Mutations affecting the eukaryotic initiation factor 2B (eIF2B) cause 1 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.

Historical note and terminology

Patients with childhood ataxia with central nervous system hypomyelination were first identified in 1992 (Schiffmann et al 1992). Similar patients were soon described (Hanefeld et al 1993; van der Knaap et al 1997a). This disorder is also known as "the vanishing white matter disease" (van der Knaap et al 1997a; van der Knaap et al 1998).

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