Disclaimer

I am not a medical expert, I'm the mother of a gorgeous little girl, Chloe who has been diagnosed with a terminal brain disease; Vanishing White Matter Disease (VWM). I have gathered the information below after many nights spent researching and corresponding with various medical experts in this field – in my quest to find answers.

Here is a brief summary of what I have found.

**** If you are reading this because someone you know has been diagnosed with VWM, please contact me directly and I will provide you with more detailed information ****

Vanishing White Matter Disease (VWM) is also known as CACH (childhood ataxia with central nervous system hypomelinization), Leukoencephalopathy with vanishing white matter and Vanishing White Matter Leukodystrophy.

It is extremely rare – there are only seven known cases in Australia and around 172 living worldwide. It’s a devastating genetic, degenerative, terminal brain disease that affects mostly children. Symptoms generally appear between the ages of two and six years old in children who were previously developing normally. Sudden uncoordinated muscle movement (cerebella ataxia); abnormal muscle stiffness (spasticity); difficulty walking or standing unaided; irritability; damage to optic nerve; epileptic seizures; delayed development; possible deterioration of mental functioning; loss of motor functions.

In a very short period of time, it causes the inability to walk, talk and eat, unable to sit unassisted, they lose the use of their hands and lose head control. Patients can have epileptic seizures, spasticity, vomiting, irritability and intellectual disability, blindness, deafness, coma and is followed by death often before reaching teenage years. Some patients die during the coma; others recover slowly, but never to the same level as before.

VWM disease is chronic and progressive with periods of relative stability followed by episodes of more rapid and severe deterioration after any of the following triggers:

- Infection with fever

- Minor head trauma (a small bump to the head)

- Emotional or physical stress

- Fright

- Amino acid starvation

- Anaesthesia

Any of the above triggers can cause the deterioration of the central nervous systems white matter – which is composed of nerve fibres and myelin. Myelin is the insulator of the nerve fibres (like insulation on electrical cables) and has two functions; to prevent short-circuits and secondly acceleration of impulse conduction along the nerve fibres. Once the myelin is damaged or disappears, the brain signals (messages) don’t get transmitted correctly from the brain to the rest of the body and brain functions become hampered or lost completely.

VWM patients deteriorate when exposed to one of the above triggers, which places an increased demand for protein synthesis (the process of making protein) by the brain. The genes required for producing a major regulator of protein synthesis – eif2B have mistakes (genetic mutations) within them. Specific brain cells are particularly sensitive to eIF2B mutations, making the slow production of abnormal myelin which gradually deteriorates and is replaced by cerebrospinal fluid (CSF) or tissue water. Life is only possible if some eIF2B activity remains.

VWM patient’s senses are heightened; hearing, smell, allergies, movement and balance are all affected with Chloe.

The severity of the disease is highly variable, depending on the mutations the patient has. Some patients die within a couple of months to a couple of years, some become wheelchair dependant after a couple of years of illness. Following an infection with fever, the patient may deteriorate for days with loss of motor skills, become lethargic, loss of vision, epileptic seizures, vomiting, irritability, depressed consciousness and finally coma.

The average life expectancy of VWM patient’s has been measured at five to ten years from onset of the disease when diagnosed in early childhood.

VWM has an autosomal recessive mode of inheritance. If both the father and mother carry a defect in the same gene, there is a 25% chance for each child they have that the child will receive both defective genes and this child will have the disease. There is a 50% chance the child will be a carrier and a 25% chance the child will be completely unaffected. As at February 2016, there are two research projects searching for a treatment/cure; The first is by Prof Orna Elroy-Stein (Tel-Aviv University) who has generated the first test model for VWM Disease. Prof Elroy-Stein has used it to screen for possible FDA approved drug compounds for treatment. She is currently working on developing the most promising drug candidate in the hope of being able to “stop the disease in its tracks”, although this testing could take up to 3 years. However with increased funding this time can be greatly reduced.

As at February 2016, there are two research projects searching for a treatment/cure; The first is by Prof Orna Elroy-Stein (Tel-Aviv University) who has generated the first test model for VWM Disease. Prof Elroy-Stein has used it to screen for possible FDA approved drug compounds for treatment. She is currently working on developing the most promising drug candidate in the hope of being able to “stop the disease in its tracks”, although this testing could take up to 3 years. However with increased funding this time can be greatly reduced.

The second is by Prof van der Knaap (VU University Medical Center, Amsterdam) whose research is working on genetically repairing defective genes using the genome editing technology method. She recently developed 2 VWM test models, which show progressive neurological dysfunction and White Matter abnormalities closely resembling human Vanishing White Matter. Once the cell therapy approach proves beneficial in VWM test model, this will be an important new strategy in treating numerous different White Matter Diseases associated with severe handicap in patients.