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Metachromatic leucodystophy (late infantile form)

Contents

Introduction
What causes MLD?
How is it diagnosed?
Does it have any alternative name?
Is it inherited?
Is prenatal testing available?
How common is it?
How does the disease progress?
Is there any treatment?
Is any research being done?

 

Introduction

This leaflet explains about Metachromatic Leucodystrophy, which is a rare inherited disorder. It mainly affects the 'white matter' of the brain, causing a progressive loss of physical and, later, mental skills.

What causes MLD?

Metachromatic Leucodystrophy (MLD) is one of a group of leucodystrophies caused by an abnormal build-up of substances (metachromatic material called sulphatides) in the nerve cells. It particularly affects the nerve cells in the white matter of the brain, which take the place of myelin, the insulating material essential for normal transmission of messages between nerves. These substances are normally broken down and removed from the body by an enzyme (arylsulphatase A) but in MLD, the gene responsible for producing the enzyme is faulty so the normal process cannot occur. As the brain is the control centre of the whole body, blockages in the messages to other parts of the body will prevent those parts working efficiently, even though the parts themselves seem quite healthy.

How is it diagnosed?

Diagnosis is made by urine tests, which show the metachromatic material (sulphatides), and blood tests, which show an absence of the enzyme (arylsulphatase A).

Does it have any alternative name?

MLD is sometimes known by its medical description, Sulphatide Lipidosis or Sulphatidosis, and the Late Infantile Form may also be called Greenfield's Disease.

Is it inherited?

MLD is an autosomal recessive disorder, which means both parents are carriers of the disease. Human beings have about 30,000 to 40,000 different genes, each of which has a function in making an individual person. The genes are arranged in pairs (one 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 MLD (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 per cent chance of the child being affected.

Is prenatal testing available?

Prenatal testing is usually possible by chorionic villus sampling early in pregnancy.

How common is it?

It is estimated that the incidence in the UK is approximately one in every 40,000 people.

How does the disease progress?

In the Late Infantile Form of MLD your child's development will start to slow down between the ages of six months and two years. He or she may become rather unsettled and appear physically floppy (hypotonic). Over the following months, motor skills will not progress as expected and skills that have been learnt will be lost. Over the next few years, your child will become as dependent as a new-born baby, usually developing stiffness of the legs (spasticity) and eventually losing all understanding or real awareness of his or her surroundings. Very rarely epileptic seizures may develop. The condition is not a painful one and your child will be unaware of what is happening in the later stages of the disease. The brain's control of the muscles responsible for chewing, coughing, swallowing and so on eventually becomes affected so that assistance with a feeding tube may be needed, and chestiness will develop and may lead to infections and increasing physical weakness. Eventually the combination of a diseased brain and physical weakness will become too great to sustain life, and death usually occurs between the ages of five and eight years. As a parent or carer, you will be aware of your child's increasing frailty, and death is usually relatively peaceful and expected when the time comes.

Is there any treatment?

Although there is no treatment yet available that can stop the disease, every effort is made to treat the symptoms as they occur. Drugs can be given to relieve muscle spasms and treat infections. Pain relief and sedative drugs can be given if required, and feeding can be assisted. Physiotherapists and others can advise parents on positioning, seating and exercising the limbs to maintain comfort. Specialist schooling will be required and it is important for your child to have this stimulating environment and social contact and, for you to have some time for yourself and other family members and friends. Though not scientifically proven, many children gain some symptomatic relief from some of the complementary therapies such as cranial osteopathy and massage. In siblings who have the disease but have not yet shown any symptoms, bone-marrow transplant may be considered as an experimental treatment but it does not benefit children who are already obviously affected.

Is any research being done?

Research is progressing in various areas concerning leucodystrophies and other progressive neurological disorders, particularly 'mapping' genes and understanding which gene is responsible for what process. However, any treatment that could reverse the disease process is unlikely to be discovered quickly enough to help children who already have symptoms. Your neurologist and information available from the support group can keep you informed of research progress.