Frequent questions and answers about MLD. Click a question to view the answer.
What is Metachromatic Leukodystrophy (MLD)?
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 by MLD?
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.
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 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.
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.
What is the prognosis?
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.
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?
Currently there is no 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.
What research is being done?
Future treatment options such as improved bone marrow transplants, gene therapy, enzyme replacement therapy and substrate reduction therapy are currently being investigated.
Is MLD contagious?
No, MLD is a genetic disorder and therefore cannot be passed to others through any form of contact.
What is the history of MLD?
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.
Does MLD have any alternative names?
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.
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