What is Vanishing White Matter (VWM) disease ?

Vanishing White Matter is a genetic disorder which destroys the brain’s white matter.  White matter is the tissue that is responsible for passing massages between the gray matter in the nervous system.  White matter gets its color from myelin sheath that surrounds the nerve fibers.  Myelin is an essential part of white matter; if it’s damaged or disappears, it slows down or fails the conduction of impulse along nerve fibers (The Vanishing White Matter).  This disorder was not recognized as a clinical syndrome until the 1990’s since than there has been research done but no cure found yet.  After that there were many cases found which showed the same symptoms for Vanishing White Matter and those cases were then used for the further research for cure.

Vanishing White Matter (VWM) is also known as Childhood Ataxia with Central nervous system Hypomyelination (CACH).  It is recessive genetic disorder which means a child has to receive two effected genes from their parents in order for this disease to be inherited and for it to develop. Effected parent has parents that are unaffected but they carry the mutated copy of the gene which makes them carriers. Which then gives the parents 25% chance of having a child that will be affected by this disorder, and 50% chance of this gene being passed on to their children which will make them a carriers and 25% chance of them not being affected at all. “This disorder is a result of mutation in any five genes encoding subunits of the translation initiation factor elF2b.  The genes are identified as EIF281, EIF262, EIF263, EIF264, and EIF265” (The Vanishing White Matter Foundation). 

Doctors diagnose Vanishing White Matter based on clinical symptoms as well as MRI, and also it can be confirmed by the use of DNA techniques, since now they know the specific genetic defect.  According to united leukodystrophy foundation “VWM is caused by changes in the genes that reduce the function of eIF2B. The reduction in elF2B function becomes a particular problem during episodes of fever, infection, or head traumas, so that clinical deterioration accelerates following such episodes” (united lekodystrophy foundation).  Some other symptoms for this disease are episodes of fever, coma, spasms, involuntary contraction of muscle, abnormality of the eyes and, mental impairment.  These symptoms are usually recognized in infancy or early childhood, but can also be seen later in the child’s development.  The development of the disorder begins through an infection with fever and/or miner head trauma.  This could cause loss of motor skills, loss of vision, epileptic seizures, vomiting, depressed consciousness and finally coma.  Some patients never wake up from coma, and for those who do weak up they recover slowly, but never to the same level they were before they went to coma.  Currently there is no cure for this disease but there are research projects done towards fining the cure.

In 1985 Marjo van der Knaap received the firs scan of a brain image which showed how the VMW develops.  She was moved by the beauty of pictures, paintings and mostly the detailed images of the brain. She combined her clinical practice with neuroscience to provide her little patients with a medical advice.  Van der Knaap specialized in group of a disease that affected the white matter in the brain and that is how she developed an MRI pattern that helped distinguish the different types of diseases associated with white matter.  Together with Doctor Jan Pronk, they identified the five genes responsible for the development of Vanishing White Matter.  Van der Knaap is very determined to find new therapies that could help with recoveries from diseases caused by loss of white matter, and one of the examples is the stem cell therapy for Vanishing White Matter.  After she won the Spinoza Award in 2008, she was determined to expend her research; it gave her the funds needed to continue her research. She gave part of her wining price to steam cell laboratory, since that could be a future for the basic treatment that she is focusing her research on.   Anita Mussche says that, van der Knaap “… is not really interested in status or ambition,” she said “Ambitious people want reach something, for instance status or position, and become frustrated if it takes too long.  I’m not like that.  I’ve got an inner drive.  I want to work, do things.  I do all I can, and I’ll see what comes of it”” (Anita Mussche).  Van der Knaap did not find the cure yet but she is not giving up on doing so.

Although not many people knew about VWM, there are other scientists that are working on finding the cure.  One of whom is Prof. Orna Elroy-Stein of Tel Aviv University’s Department of Cell Research and Immunology.  She started out her research by using yeast, and then later developed her research using mice.  She conducted this research not only to solve the problem with finding the cure but also to understanding the process of this diseases development.  According to Prof. Orna Elroy-Stein the understanding of this disease is the first step to finding the cure.  She began her case study on mice after Tom O’Brien’s daughter passed away due to the Vanishing White Matter.  O’Brien adopted Marisol from Latin America.  When she was born she was developing normally, but then when she was 3 years old, Marisol begin to limp. After many visits to the doctors she was diagnosed with Vanishing White Matter, which later caused her to lose the ability to move, eat, speak and made her prone to seizures and spasms.  O’Brien was looking for miracles; he remembers when one day at the National Institutes of Health doctor scraped a little piece of Marisol’s skin and send it to Israel’s doctor who was researching causes and progress of her disorder.  Even though the doctors never met her, they felt like they knew her.  Marisol’s picture was posted at their desks as they studied her disease, it helped them in  not giving up on this research no matter how many dead ends they hit.  Later on in the research, O’Brien wanted to see what has become of this journey, what has been done and what still needs to be done to find the cure.  He visited Professor Elroy-Stein and her researchers at the lab to see the mice.  When he walked in to the lab room he said that he could feel the presence of his little girl.  During his visit he said, “It’s so hard when you go through something like this, you have a lot of questions, and they don’t have answers, they’re for God.  Why did the disease process the way it did?  Why did she have to be in pain?  Why did she have to die?” (O’Brien; Yvonne Abraham)  He also said that Marisol’s purpose of being might have been to help find the cure.  O’Brien’s foundation is still raising funds to support Prof. Orna Elroy-Stein research.

Pr. Raphael Schifmann is also one of the professors working on finding the cure.  He became interested in it in 1991, when he came across a patient who was diagnosed with Vanishing White Matter which was at the time when he was working as Clinical Fellow at the National Institute of Neurological Disorders and Stroke.  After that he started studying leukodystrophy syndromes.  According to Pr. Schiffmann, MRI was and still is one of the methods of diagnosing leukodystrophies. Till this day the pattern on the MRI is the most useful diagnostic tool in the VWM.  Pr. Schiffmann said that this technology has improved over the years with better qualities resolution of the MRI image.  Also DTI and MRS are used if defining the pattern of the abnormality of the brain, and CT scan is still the most sensitive and thus useful tool. 

The Vanishing White Matter is a genetic disorder which has been around since 1990’s.  It is a disorder which took lives of many children, it took their lives before they had the chance to experience what every child should.  The VWM is a disorder with no cure found yet, but there are many researchers working on finding one.  This research is done to find what many families are looking and hopping for, the cure for the once they love.

Works Cited

Marjo S. van der Knaap, et al. "Characteristics Of Early MRI In Children And Adolescents With Vanishing White Matter." Neuropediatrics 43.1 (2012): 22-26. Academic Search Complete. Web. 2 May 2013.

Wilson, C.J., J.C. Pronk, and M.S. Van der Knaap. "Vanishing White Matter Disease In A Child Presenting With Ataxia." Journal Of Paediatrics & Child Health 41.1/2 (2005): 65-67. Academic Search Complete. Web. 30 Apr. 2013.

http://www.youtube.com/watch?v=U_S2ecC7WNc 

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