About MLD

Metachromatic leukodystrophy (MLD) is a rare genetically inherited disease that affects 0.001% of the population. There are 4 forms to the disease: Late Infantile (LI), Early Juvenile (EJ), Late Juvenile (LJ) and Adult Onset; all of which result in life-long disability and premature death.

Patients with MLD lack of an important enzyme called arylsulfatase A, which causes toxic material to build up and damage the myelin sheath covering the nerve fibres of the brain and nervous system. Patients progressively lose function affecting speech, memory, movement, sight, hearing, touch, eating and swallowing. Other areas of the body are commonly affected, including the gall bladder. It is one of a number of known genetic demyelinating diseases or leukodystrophies. It is also known as an ‘Inherited Metabolic Disorder’ (IMD).

Life expectancy varies depending on what age the condition started. Generally speaking, the earlier the disease onset the more quickly the disease progresses. The disease is caused by defective genes. You must get a copy of a defective gene from both of your parents to have the disease. Parents can each have a defective gene, but not have MLD.

The only current treatment options for MLD are best supportive care and gene therapy in a relatively small number of cases. Gene therapy, known in the UK as ‘Libmeldy’, is currently licensed for use by NHS England where there is a pre-symptomatic diagnosis of Late Infantile MLD or an early symptomatic diagnosis of the Early Juvenile form of the disease.

Catching cases at birth would unquestionably save lives, which we why we are leading the work required to have MLD added to the UK newborn heel prick test.

There are three types of MLD:

Life expectancy varies depending on what age the condition started, but the disease course usually runs 3 to 20 years or more. The earlier the age at diagnosis, the more quickly the disease progresses. Most children with the infantile form do not live past the age of five. Children with the juvenile form can live for up to 10 to 20 years after symptoms are first noticed. Adult cases have a greater life expectancy.

The disease is passed down through families. You must get a copy of the defective gene from both your parents to have the disease. Parents can each have the defective gene, but not have MLD.

There are a number of support groups and non-profit organisation world-wide who help raise awareness of such diseases and help prevent sufferers from feeling isolated, please see FAQ below

Although there is currently no cure, research into MLD is being carried out in labs and hospitals throughout the world. Some progress has been made through Gene Therapy, and transplantation of the patient’s own bone marrow cells, at San Raffaele Hospital in Milan, Italy. Other groups are developing different therapies, including Biotech company Shire, who is trialling an enzyme replacement therapy. More information can be found at clinicaltrials.gov

What is Metachromatic Leukodystrophy?

Metachromatic leukodystrophy is an inherited disorder characterised by the accumulation of fats called sulfatides in cells. This accumulation especially affects cells in the nervous system that produce myelin, the substance that insulates and protects nerves. Nerve cells covered by myelin make up a tissue called white matter. Sulfatide accumulation in myelin-producing cells causes progressive destruction of white matter (leukodystrophy) throughout the nervous system, including in the brain and spinal cord (the central nervous system) and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system)

In people with metachromatic leukodystrophy, white matter damage causes progressive deterioration of intellectual functions and motor skills, such as the ability to walk. Affected individuals also develop loss of sensation in the extremities (peripheral neuropathy), incontinence, seizures, paralysis, an inability to speak, blindness, and hearing loss. Eventually they lose awareness of their surroundings and become unresponsive. While neurological problems are the primary feature of metachromatic leukodystrophy, effects of sulfatide accumulation on other organs and tissues have been reported, most often involving the gallbladder.

Who is affected ?

The most common form of metachromatic leukodystrophy, affecting about 50 to 60 percent of all individuals with this disorder, is called the late infantile form. This form of the disorder usually appears in the second year of life. Affected children lose any speech they have developed, become weak, and develop problems with walking (gait disturbance). As the disorder worsens, muscle tone generally first decreases, and then increases to the point of rigidity.

Individuals with the late infantile form of metachromatic leukodystrophy typically do not survive past childhood. In 20 to 30 percent of individuals with metachromatic leukodystrophy, onset occurs between the age of 4 and adolescence. In these early and late juvenile forms, the first signs of the disorder may be behavioural problems and increasing difficulty with schoolwork. Progression of the disorder is slower than in the late infantile form, and affected individuals may survive for about 20 years after diagnosis.

The adult form of metachromatic leukodystrophy affects approximately 15 to 20 percent of individuals with the disorder. In this form, the first symptoms appear during the teenage years or later. Often behavioural problems such as alcoholism, drug abuse, or difficulties at school or work are the first symptoms to appear. The affected individual may experience psychiatric symptoms such as delusions or hallucinations. People with the adult form of metachromatic leukodystrophy may survive for 20 to 30 years after diagnosis. During this time there may be some periods of relative stability and other periods of more rapid decline.

What are the symptoms?

There is a breakdown in communication between the nerves and brain, causing progressive loss of acquired functions, paralysis, blindness and seizures, eventually leading to death. The late infantile form sees children have difficulty with walking after the first year of life and symptoms include muscle wasting and weakness, muscle rigidity, developmental delays, loss of vision and blindness, convulsions, impaired swallowing, paralysis and dementia.

Initial symptoms of the juvenile forms are usually impaired school performance, mental deterioration and dementia, before symptoms similar to the infantile form develop with slower progression. The adult form begins as a psychiatric disorder or progressive dementia and the symptoms progress more slowly, often spanning a decade or more.

How common is MLD?

Metachromatic leukodystrophy is reported to occur in 1 in 40,000 to 160,000 individuals worldwide. The condition is more common in certain genetically isolated populations: 1 in 75 in a small group of Jews who immigrated to Israel from southern Arabia (Habbanites), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How is MLD diagnosed?

An MRI brain scan may initially suggest the diagnosis. Further confirmation can be found through a urine test, showing the metachromatic material (sulphatides) and a blood test, which shows the absence of the ARSA enzyme.

Is there any treatment?

For most cases, the only current treatment options involve best supportive care, with multiple medications and possible surgeries to manage symptoms. Gene therapy, which corrects a patient’s faulty DNA to enable them to start producing the ARSA enzyme, is available in a relatively small number of cases.

Gene therapy, known as ‘Libmeldy’, is currently licensed for use by NHS England where there is a pre-symptomatic diagnosis of Late Infantile MLD (usually only detected where there is an established case of MLD in the family) or an early symptomatic diagnosis of the Early Juvenile form of the disease.

The team at ArchAngel are not qualified to give clinical or emotional support to suffering families, however we work closely with these excellent organisations who can help deal with this type of issue: