Metachromatic leukodystrophy (MLD) is a rare genetically inherited disease that affects 0.001% of the population. There are 3 forms to the disease, all of which result in life-long disability or death.
MLD, in plain speak, is a rare disease affecting about one in 100,000 people, where the lack of an important enzyme called arylsulfatase A causes your brain and nervous system to progressively lose function affecting: speech, memory, movement, sight, hearing, touch, eating and swallowing.
In scientific terms, MLD attacks the myelin sheath covering the nerve fibres of the brain. It is one of a number of known genetic demyelinating diseases or leukodystrophies.
It affects the body in ways not yet fully understood but we do know that there’s an accumulation of a fatty substance which affects the white matter of the brain and other areas of the body (liver, gall bladder, kidneys, and/or spleen), it gets worse over time, and there is currently no cure for MLD.
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
Click a question below to view the answer.
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.
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 this juvenile form, the first signs of the disorder may be behavioral 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 behavioral 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.
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 form 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.
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.
Children with the infantile form have a maximum life expectancy of five years, but usually pass before that. Those with the juvenile form have a life expectancy of 10 to 15 years after symptom onset, although some juveniles can live for several decades after. Adult MLD usually progresses much slower, with a course of a decade or more after onset.
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.
Although clinical trials are in progress, currently there is no established cure for MLD. Bone marrow transplantation may delay the progression of the disease in some infantile cases or juvenile and adult cases who display mild to moderate symptoms. Drugs can be given to help relieve muscle spasms, treat infections and control seizures, and pain relief and sedative drugs can be provided if required.
Future treatment options such as improved bone marrow transplants, gene therapy, enzyme replacement therapy and substrate reduction therapy are currently being investigated. More information can be found at clinicaltrials.gov
No, MLD is a genetic disorder and therefore cannot be passed to others through any form of contact.
MLD was first reported in 1933, with the account credited to Dr Joseph Godwin Greenfield, a professor of pathology and clinical medicine at what is now called the National Hospital for Neurology & Neurosurgery. Due to this, MLD was previously known as Greenfield's Disease. The first published reports of MLD were in the 1960s and the first experimental bone marrow transplant treatments took place in the early 1980s.
MLD may also be referred to as Arylsulfatase A deficiency or its medical descriptions Sulphatide Lipidosis or Sulphatidosis. MLD was also previously known as Greenfield's Disease due to the first report being credited to Dr Joseph Godwin Greenfield.