MEGALENCEPHALIC LEUCOENCEPHALOPATHY
Introduction
Megalencephalic Cystic Leucoencephalopathy (MCL1) is a very rare disorder affecting the ‘white matter’ of the brain, sometimes causing intermittent episodes of illness, leading to progressive loss of physical, and sometimes mental, skills over very many years.
What is the cause?
MCL1 is a demyelinating disorder, one of a group of diseases called Leucodystrophies. In these disorders myelin deteriorates and is eventually lost. Myelin is the insulating material surrounding all nerves in the body and is necessary for the transmission of messages ( it can be compared to insulation around electric wires). In these diseases the myelin loss mainly affects the nerves in the brain but, as all instructions controlling movement come from the brain, it affects the limbs and , eventually, the thought processes. This demyelination is presumed to be due to a chemical abnormality caused by a, as yet unidentified, faulty gene.
How is it diagnosed?
The diagnosis is made, initially ,on the history of the child’s symptoms; eventually an MRI brain scan shows loss of white matter/ myelin ( Leucodystophy),swelling and cysts in the temporal or parietal areas of the brain which are characteristic of MCL1; these scan features, however, may not be apparent until several years have elapsed.
Does it have an alternative name?
In the late 1990s, Dr Van der Knaap described this particular form of Leucodystrophy, based on the features of the condition and the specific findings on the brain scan. It was sometimes known as Van der Knapp Leucodystrophy
Is it inherited?
MCL1, like most of the other Leucodystrophies, is an autosomal recessive disorder; this means that both parents are carriers of the disease. Human beings have about
30 – 40,000 different genes, each of which has a function in making an individual person. The genes are arranged in pairs ( 1 of the pair from each parent) on 23 chromosomes. Inevitably, some of these genes are faulty; a normal gene can overcome a faulty one, but if both genes in the pair are faulty, the genetic instructions cannot work. Most people carry different faulty genes but in MCL1 (and other recessive conditions) parents, though healthy themselves, carry the same faulty genes, and risk passing them on to their children.
Each pregnancy carries a 25% chance of the child being affected
a 75% chance of the child NOT being affected
Is prenatal testing available?
At present there is no way of telling whether an unborn baby will be affected.
How common is it?
It is estimated that the incidence in the UK is approximately 1: 500,000
How does the disease progress?
The infant will have no apparent problems in the first year but, if measured, the head size may be noted to be larger than expected; between the ages of 2 – 10 years the child shows signs of increasing unsteadiness( ataxia) followed by stiffness in the limbs
( spasticity) and, after very many years, progressive loss of mental skills; epileptic seizures may or may not develop in the later stages of the disease process. As yet, very few children have been recognised as having the disease and it appears that the age at which different symptoms and difficulties arise can vary greatly, but children are likely to be wheelchair users, in mainstream school, in the teenage years. The long term prognosis is, as yet, uncertain as the condition has not been recognised long enough for the children to have reached adulthood but, based on experience of other similar diseases, it has to be presumed that the combination of the diseased brain and physical weakness becomes too great to sustain life and that early death is, sadly, inevitable. By this time the young adult will be unlikely to be aware of what is happening but family and carers will be aware of his/her increasing frailty and death would be expected to be relatively peaceful and expected when the time comes.
Is there any treatment?
Although there is no treatment yet available that can stop the disease process, every effort is made to ensure that the child and young adult enjoys as much independence and life- experiences as his/her friends. Help will be provided with mobility aids when necessary and any symptoms, including possible seizures, will be treated if and when they occur in the later stages of the disease. As more is understood of the biochemical basis of the disease, possible treatments are likely to be tried and, when the gene is eventually found, replacing faulty with healthy genes could possibly be considered.
Is any research being done?
Research is progressing both on the understanding of the biochemistry and finding out what all the different genes are responsible for, so that ‘faulty’ genes can be recognised. This would enable prenatal testing to be possible and eventually, it is hoped, replacement of the faulty gene(s). Unfortunately this research is extremely complex and may seem very slow to the sufferer and his/ her family. Your neurologist and information available from the support group can keep you informed of research progress.
Is there a Support Group?
The Research Trust for Metabolic Diseases in Children: CLIMB, which includes the Leucodystophies, can provide written information, telephone advice, support and contact ( if wanted) with other families:-
CLIMB
Climb Building
176 Nantwich Road
Crewe CW2 6BG
Tel: 0800 652 3181
e-mail: [email protected]
Mostyn GOSH 2005