Childhood Ataxia with CNS Hypomyelination, or CACH, is a leukodystrophy, a group of more than 15 rare genetic disorders that cause progressive degeneration of the white matter of the brain due to imperfect growth or destruction of the myelin sheath, the fatty covering that insulates nerve fibers in the brain and spinal cord and promotes rapid transmission of nerve impulses. Without myelin, nerve cells cease to function and eventually die. As myelin deteriorates in leukodystrophies such as CACH, nervous system function is impaired. The leukodystrophies are often referred to as “demyelinating” diseases.
CACH, also referred to as Vanishing White Matter Disease (VWM), is an inherited autosomal recessive disorder. Symptoms generally appear in young children who may have initially appeared to be developing normally. However, it has been shown recently that symptoms may appear at or shortly after birth – or even in adulthood. A striking feature of the disease is that symptoms get worse slowly for the most part, but there are episodes of rapid deterioration that follow fever, infection or head trauma. The patient may have a partial recovery following these episodes, or the episode may lead to coma and death.
CACH / VWM, is caused by mutations in one of the five genes (collectively called eIF2B, or eukaryotic initiation factor 2B) necessary to make proteins in the body; it is so important that no one can be born with a complete absence of this gene. Changes in these genes reduce the function of eIF2B. This reduction in function becomes a particular problem during episodes of fever, infection or head trauma, and deterioration accelerates following such episodes.
Generally, a child with CACH / VWM will appear relatively normal at birth, though he/she may have slightly delayed psycho-motor development. Symptoms may appear beginning in late infancy or early childhood, and can vary widely from case to case.
Possible symptoms and definitions include:
- Neurological deterioration
- Episodes of fever (in VWM, this is associated with worsening of symptoms, drowsiness or coma.
- Spasticity, or involuntary muscle contractions resulting in abnormally stiff muscles and restricted movement.
- Lethargy, or abnormal drowsiness and indifference to environmental stimuli
- Coma
- Ovary dysgenesis, or defective development of the ovaries.
- Cerebellar ataxia, or loss of muscle coordination as a result of abnormal functioning of the cerebellum (a part of the brain).
- Optic atrophy, an abnormality of the eyes.
- Seizures
- Mental impairment may be present, though generally less severe than motor dysfunction
The motor difficulties of CACH / VWM are progressive, but the progression is often stepwise in association with fever or injuries. Prolonged periods of stability or even transient mild improvements lasting years are common. Most patients develop seizures (epilepsy) late in the illness that are easy to control. Life expectancy is reduced, though patients can live into their second or third decades.
The most common leukodystrophies include Canavan disease, Krabbe disease, metachromatic Leukodystrophy (MLD), Childhood Ataxia with Central Nervous System Hypomyelination (CACH), Alexander disease and Refsum disease.