CACH syndrome

CACH syndrome, also known as Childhood Ataxia with Central Nervous System Hypomyelination or Vanishing White Matter Disease (VWM), is a rare inherited leukodystrophy that primarily affects the brain's white matter. The disease is caused by mutations in genes encoding the five subunits of eukaryotic translation initiation factor 2B (EIF2B1, EIF2B2, EIF2B3, EIF2B4, or EIF2B5), which plays a critical role in protein synthesis. The condition leads to progressive deterioration of the white matter in the brain, which is essential for transmitting nerve signals between different brain regions. The hallmark features of CACH syndrome include progressive cerebellar ataxia (difficulty with coordination and balance), spasticity (muscle stiffness), and cognitive decline. A distinctive characteristic of this disease is that neurological deterioration can occur in episodes, often triggered by febrile infections, minor head trauma, or acute fright. Between episodes, patients may partially recover, but over time there is progressive neurological decline. Brain MRI characteristically shows diffuse white matter abnormalities with areas that appear to be replaced by fluid, giving rise to the term 'vanishing white matter.' Additional features may include optic atrophy and, in females, premature ovarian failure (ovarioleukodystrophy). The age of onset and severity are highly variable. The most common form presents in early childhood, typically between ages 2 and 6, but neonatal, infantile, juvenile, and adult-onset forms have been described. Earlier onset generally correlates with more severe disease. There is currently no cure or disease-modifying treatment for CACH syndrome. Management is supportive and focuses on avoiding known triggers of deterioration, physical therapy, management of spasticity, and symptomatic care. Patients and families are advised to avoid head trauma and to manage fevers aggressively. Prognosis varies depending on the age of onset, with earlier-onset forms typically having a more rapid and severe course.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about CACH syndrome