Myelinosis centralis diffusa, Cree leukoencephalopathy (infantile form), Childhood Ataxia with diffuse CNS hypomyelination (CACH), Ovarioleukodystrophy
Inheritance from both parents will result in the disease
Age range at onset:
Usually age 2-3 years
Possible in later childhood or even adulthood
Specialists you may see:
The severity of symptoms of Vanishing White Matter Disease is greatly affected by the age of onset: antenatal onset will lead to death within a few months, while those presenting first symptoms in adulthood will have only mild neurological problems. Fatal infantile forms are also known as Cree Leukoencephalopathy, while juvenile and adult forms can be called Ovarioleukodystrophy.
Symptoms of the condition progress over time with periods of rapid deterioration caused by stressors such as infection and head trauma. Partial recovery from these episodes is possible; more severe episodes result in coma or death. Loss of motor skills is often the first noticeable symptom, perhaps triggered by one of these stressors. Chronic neurological deterioration follows, with cerebellar ataxia, spasticity and seizures. Those with Vanishing White Matter Disease may experience lethargy and some mental decline, as well as optic atrophy. Females may suffer from ovarian dysgenesis, which can cause fertility problems and early menopause.
Mutations in the five genes which encode the protein eIF2B, namely eIF2B1, eIF2B2, eIF2B3, eIF2B4 and eIF2B5, cause Vanishing White Matter Disease. This protein is used to produce all other proteins, so survival is not possible in the absence or malfunction of these genes. In Vanishing White Matter Disease, small changes to these genes reduce the function of eIFB2. This reduced functioning makes the body vulnerable, particularly during fevers, infections or head trauma.
Mutations in AARS2 cause an adult onset leukodystrophy causing dementia, upper motor neuron signs and ataxia. Ovarian failure is common in females with these mutations.