MLD diagram of neuron showing location of Myelin sheath

About MLD

MLD is an acronym for Metachromatic Leukodystrophy.  MLD is a genetic disorder which at the moment has no cure. MLD is directly caused by a deficiency of the enzyme Arylsulfatase A and is usually characterized by enzyme activity which is less than 10% of human controls. Without this enzyme, sulfatides build up in many tissues of the body, eventually destroying the myelin sheath of the nervous system.  The myelin sheath is a fatty covering that protects nerve fibres. Without it, the nerves in the brain (central nervous system — CNS) and the peripheral nerves (peripheral nervous system — PNS) which control, among other things the muscles related to mobility, cease to function properly.


Symptoms and types of MLD

Like many other genetic disorders that affect lipid metabolism, there are several forms of MLD, which are generally classified as late-infantile, juvenile, and adult.


Late Infantile MLD

In the late infantile form, which is the most common form of MLD (50-60%), affected children begin having difficulty walking after the first year of life, usually at 15–24 months. Symptoms include muscle wasting and weakness, muscle rigidity, developmental delays, progressive loss of vision leading to blindness, convulsions, impaired swallowing, paralysis, and dementia. Children may become comatose. Untreated, most children with this form of MLD die by age 5, often much sooner.


Juvenile MLD

Children with the juvenile form of MLD (onset between 3 and 10 years of age) usually begin with impaired school performance, mental deterioration, and dementia and then develop symptoms similar to the late infantile form but with slower progression. Age of death is variable, but normally within 10 to 15 years of symptom onset although some juveniles can live for several decades or longer after onset.


Adult-Onset MLD

The adult form of MLD commonly begins after age 16 and, in the initial stages, is often mis-diagnosed as a psychiatric disorder because of personality changes. Initially, the symptoms are cognitive rather than physical, then leading to progressive dementia and, ultimately, physical disability as well. Adult-onset MLD progresses more slowly than the late infantile and juvenile forms, with a protracted course of a decade or more.

Palliative care can help with many of the symptoms and usually improves quality and longevity of life.



MLD has an autosomal recessive inheritance pattern. The inheritance probabilities per birth are as follows:

If both parents are carriers (possibly the most common incidence):

  • 25% (1 in 4) children will have the disorder
  • 50% (2 in 4) children will be carriers (but unaffected)
  • 25% (1 in 4) children will be free of MLD – unaffected child that is not a carrier

If one parent is affected and one is free of MLD:

  • 0% (0) children will have the disorder – only one parent is affected, other parent always gives normal gene
  • 100% (4 in 4) children will be carriers (but unaffected)

If one parent is a carrier and the other is free of MLD:

  • 50% (2 in 4) children will be carriers (but unaffected)
  • 50% (2 in 4) children will be free of MLD — unaffected child that is not a carrier

In addition to these frequencies there is a ‘pseudo’-deficiency that affects 7% of the population. People with the pseudo deficiency do not have any MLD problems unless they also have affected status. Pseudo-deficiency tests as low enzyme levels but sulfatide is processed normally so MLD symptoms do not exist.

Carriers have low enzyme levels compared to their family population (“normal” levels vary from family to family) but even low enzyme levels are adequate to process the body’s sulfatide. In the UK it is generally accepted that normal enzyme level is between 23 – 103.



The incidence of Metachromatic Leukodystrophy is estimated to occur in 1 in 40,000 to 1 in 160,000 individuals worldwide. However, until very recently MLD has been misdiagnosed or not diagnosed at all so it is quite possible that the incidence may be as high as 1 in 20,000.

About us

MLD Support Association UK was set up to bring hope to families in the fight to eradicate Metachromatic Leukodystrophy (MLD). Our aim is to provide support by way of shared information from people in similar circumstances who have already experienced the effects of the condition and/or any treatments available.

MLD Support Association UK

MLD Support Association UK is a
Registered Charity Number 1150542

Professor Timothy M Cox, MD, FRCP, FMedSci
Suzi Digby (Lady Eatwell) OBE
Iain Stewart MP


MLD Support Association UK
Floor 5
Amphenol Business Complex
Thanet Way

Tel: 07977 440809