What is Metachromatic Leukodystrophy?
Photo: Loie Hammond, 6/26/10-1/27/14, MLD
Those affected by MLD typically appear healthy until onset, or when an individual experience symptoms of the disease. Onset can vary from the first few weeks or months of life (Early Infantile Onset) into adulthood (Adult Onset).
Individuals affected by MLD lack an important enzyme in their blood called Arylsulfatase-A, or ARSA.
Why is the ARSA enzyme needed in the body?
ARSA is needed for the body to make normal myelin and to break down substances called sulfatides. Without this essential enzyme, sulfatides increase in the brain, central and peripheral nerves, liver and kidneys.
The accumulation of sulfatides are usually most obvious in the white matter of the central nervous system (CNS) and the peripheral nervous system (PNS). Sulfatides cause the breakdown of the myelin sheath, referred to as “demyelination”, resulting in permanent damage to the nerves.
How do you get MLD?
MLD is genetic, which means that it is an inherited disorder. MLD is an autosomal recessive genetic defect, meaning that if both parents are carriers of the disease, each child has a 1 in 4 chance of developing MLD.
When both parents pass on a specific mutated gene, such as those for MLD, their child has a 25% chance of being affected by the disease, a 25% chance of neither being a carrier nor affected, and a 50% chance of being an unaffected carrier, just like their parents. See illustration below.
Could other children in the family also have MLD?
If both parents are carriers of MLD, each child has a 1 in 4 chance of being affected. To determine if other children in the family are affected by MLD, it is important to consult with your genetic counselor or your child’s physician.
How is MLD diagnosed?
A proper diagnosis is a confirmation of the deficiency of the missing enzyme and the resulting lowered Arylsulfatase-A (ARSA) activity in the body. This diagnosis is confirmed and validated by a number of procedures, with the more common procedures including blood testing, urine testing and imaging studies.
Unfortunately, MLD is often misdiagnosed, sometimes several times before the correct diagnosis is made. Common misdiagnoses for MLD include Cerebral Palsy, Batten’s Disease, and ADHD – especially with children. In adults, since the presentation is often first psychological not physical, it can be misdiagnosed as a variety of psychological conditions.
What are the different forms of MLD?
No matter what form of MLD an individual is diagnosed with, optimal care is of timely importance. The Leukodystrophy Care Network (LCN) was established to provide individuals with the best quality of care at specialized centers across the country.
For more information and to find a Leukodystrophy Care Center nearest you, please visit the Leukodystrophy Care Network page.
There are three main types of MLD – Late Infantile, Juvenile and Adult onset. It should be noted that the type of MLD normally remains consistent within a family.
Late Infantile MLD is characterized by normal development the first 6-18 months. This is followed by a progressive regression that shows first in motor skills, perhaps never learning to walk or showing deterioration of balance. The regression will rapidly affect speech, overall mobility, and basic cognitive skills.
Often the muscles will painfully cramp up (rigidity), and feeding requires a G-tube or J-tube directly to the digestive system. Paralysis and blindness are often reported with a prognosis of 1-2 years, although today’s care usually extends that period to 5-7 years after diagnosis.
Juvenile MLD is characterized by normal development with an onset between ages 4-14. Onset usually starts with either motor or cognitive symptoms, typically not both. With the motor progression, the first signs are often changes in gait (balance/walking). Cognitive progression often begins with unexplainable behavioral outbursts accompanied by lack of memory of recent events, inability to follow simple sequences and a decline in social skills. These skills will continue to decline, along with loss of continence control, over a period of 4-8 years. Speech ability will also decline during this time.
The regression is slower than in the late infantile form, but the pattern is similar affecting mobility, eating, speech and cognitive skills. Eventually the muscle tone is lost, and cramping or stiffness might occur. Safety in swallowing/feeding requires a G-tube or J-tube. Paralysis and blindness are often reported with a life expectancy of 6-8 years, however, there are reports of a slower degeneration in this group with individuals maintaining mobility and basic cognitive skills 10-12 years or more after onset.
Adult MLD is characterized by normal development through puberty with symptoms presenting at a later age, generally from the twenties through the forties. Similar to the Juvenile cognitive form, the initial signs of adult onset are often changes in cognitive abilities and personality. The affected individual may show poor school or work performance, anxiety, bewilderment, loss of alertness, disorganization, poor judgment and/or show declining memory. Often this may be covered up or compensated for by alcoholism or other similar behaviors. Cognition, speech and balance/mobility skills will regress along with a loss of continence over a period of years. There is very little published data about the prognosis of adult onset MLD. Again, the regression is slower than in the juvenile form, but the pattern is similar.
Is there a treatment for MLD?
Individuals affected by MLD who are diagnosed before the disease is too far progressed may be eligible for an umbilical cord blood or bone marrow transplant. Through this procedure, stem cells from donated umbilical cord blood or bone marrow containing normal levels of the ARSA enzyme are given to the patient to stop the progression of the disease.
Unfortunately, this treatment is not effective in repairing myelin that has already been damaged.
For a cord blood transplant, stem cells come from umbilical cords that are donated and stored after live, healthy births of unaffected donors. To learn more about donating your baby’s umbilical cord, please visit the Carolina Cord Blood Bank.
Although there is currently no cure for MLD, symptoms can be well-managed.
With proactive, comprehensive medical care, affected individuals can avoid unnecessary suffering and complications to have the best quality of life possible. For more information, visit the Leukodystrophy Care Network page.
What if my child was diagnosed too late for a transplant?
If an individual is not eligible for transplant, proactive multidisciplinary care is essential to provide the best quality of life possible. There are a variety of therapies, adaptive equipment, and medications available for this very purpose.
Newborn screening for MLD is currently being validated in a medium-scale pilot study by University of Washington investigators. This would help in early detection of more individuals with MLD who could potentially benefit from transplant.
All families and caregivers of individuals affected by Leukodystrophy, whether they qualify for transplant or not, should seek expert care through the Leukodystrophy Care Network, or LCN.
What research is being done to find better treatments & a cure for MLD?
Hunter’s Hope is committed to funding research for better treatments and a cure for MLD and other Leukodystrophies. To learn more about the groundbreaking research currently underway, visit the Research section of our website.
Additional Resources for Families
Leukodystrophy Care Network
Hunter’s Hope Foundation – Family Care
Hunter James Kelly Research Institute
Duke Children’s Hospital: Bone Marrow and Stem Cell Transplantation
Leukodystrophy Center of Excellence – Children’s Hospital of Philadelphia
Additional Resources for Medical Professionals
National Institutes of Health: Metachromatic Leukodystrophy
Mayo Clinic: Metachromatic Leukodystrophy
US National Library of Medicine: Metachromatic Leukodystrophy
National Organization for Rare Disorders (NORD) – Metachromatic Leukodystrophy
A Special Thank You
Thank you to Matt and Lauren Hammond, parents of Loie Hammond (MLD), for the content provided on this page.