Childhood Ataxia with Central Hypomyelination; Childhood ataxia with diffuse central nervous system hypomyelination; CACH Syndrome; Leukoencephalopathy with Vanishing White Matter Disease; Leukoencephalopathy with Vanishing White Matter Myelinosis Centralis Diffusa; Cree Leukoencephalopathy; Cree Leukodystrophy

Childhood Ataxia with Central Nervous System Hypomyelination/Vanishing White Matter Disease (CACH-VWM) is a progressive disorder that mainly affects the brain and spinal cord (central nervous system). This leukodystrophy disorder causes deterioration of the CNS white matter, which consists of nerve fibers covered by myelin. Myelin is the fatty substance that insulates and protects nerves. In most cases, children with CACH-VWM show no signs or symptoms of the disorder at birth. Affected children may have slightly delayed development of motor skills such as crawling or walking. During early childhood, previously healthy children begin to develop motor impairments, including abnormal muscle stiffness (spasticity) and difficulty with coordinating movements (ataxia). There may also be some deterioration of mental functioning, but this is not usually as pronounced as the motor impairments. Specific changes in the brain are seen using magnetic resonance imaging (MRI) are characteristic of CACH-VWM and may be visible before the onset of symptoms.

Diagnostic testing: The diagnosis of CACH-VWM is made by:

• •

  Physical examination;

• •

  MRI demonstrating bilateral cerebral destruction of white matter; and

• •

  Genetic testing documenting mutations in one of the five causative gene mutations (EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5).

Physical findings: Affected children with CACH-VWM may have:

• •

  Slightly delayed development of motor skills such as crawling or walking;

• •

  Cerebellar ataxia (inability to coordinate balance, gait, extremity and eye movements);

• •

  Hypotonia (decreased muscle tone);

• •

  Spasticity (muscle stiffness or tightness);

• •

  Difficulty swallowing (bulbar symptoms);

• •

  Optic atrophy; and

• •

  Lethargy (lack of energy and enthusiasm).

ICD-9: 330.0

With CACH-VWM, generally the earlier onset of symptoms and signs correlates with faster progression and worse prognosis. In congenital or antenatal form, onset is in utero and newborns present with hypotonia, feeding difficulties, and microcephaly; progression is rapid with systemic involvement, development of intractable seizures, coma, and death before age 1. The infantile form has onset in the first months of life, similar rapid progression, motor dysfunction, and death usually by age 2 years. The early childhood onset form is the most common with onset between 1 and 5 years, with less spasticity and usually no cognitive decline. Most children with the early childhood form die within a few years of onset. In older children, adolescents, and adults, the clinical course is usually more slowly progressive than earlier onset forms, with spastic diplegia and ataxia, relative sparing of cognition, and typically longer survival.

Currently there is no cure for CACH-VWM disease. Treatment is symptom specific and supportive. Physical therapy and rehabilitation may be prescribed for motor dysfunction (e.g. spasticity and ataxia); antiepileptic drugs for seizures. Referral to age-appropriate early childhood intervention program or special education.

Suggested MER for Evaluation:

• •

  Clinical history and examination that describes the diagnostic features of the impairment;

• •

  Imaging studies; and

• •

  Genetic testing revealing a mutation in the EIF2B gene is definitive.