Metachromatic leukodystrophy


What are the main symptoms of metachromatic leukodystrophy?

People with MLD will have a low or absent level of the ARSA enzyme.

Clinical features of MLD vary depending on the type of MLD that has been diagnosed (late-infantile, juvenile, or late/adult-onset).

In general, early symptoms of MLD can be vague and gradual in onset, making it a difficult condition to diagnose. In the late-infantile type, infants may appear health at first. Before the age of 2, however, these children may develop difficulty walking, muscle wasting, weakness, developmental delay, and vision loss. In other types, early symptoms can include subtle changes in thought processing (mentation), memory, and/or posture. Sometimes the earliest symptom is a disturbance in vision, or numbness somewhere in the body. Other symptoms can also include vision problems leading to blindness, personality changes, and motor disturbances such as clumsiness, muscle weakness, rigidity, inability to coordinate movement, and/or muscle spasms especially of the neck, spine, arms, and legs, abdominal distention, difficulty speaking, loss of previously acquired intellectual skills, general mental deterioration, and/or seizures. As the symptoms of metachromatic leukodystrophy progress, blindness, paralysis, psychosis, and/or dementia may develop. People with metachromatic leukodystrophy may also experience peripheral neuropathy, which is a disorder of the peripheral nervous system (all the motor and sensory nerves connecting the brain and spinal column to the rest of the body). Common findings associated with peripheral neuropathy may include muscle weakness; pain; numbness; redness; and/or burning or tingling sensations in the affected areas, especially the arms and legs, though features of peripheral neuropathy can be variable.

Children with juvenile MLD show symptoms of disease before six years of age, but symptoms can start anytime between four years and 12-14 years. In the past, juvenile MLD has included patients diagnosed up to age 18. However, currently patients with symptoms that started after 14 year of age are diagnosed with adult MLD. Symptoms of juvenile MLD typically start in the early years of schooling. They include behavioral problems/differences, and worsening school performance. Some doctors may separate early-onset juvenile from late-onset juvenile forms of MLD. In early-onset juvenile MLD, symptoms such as clumsiness and gait problems may be noticed first. In late-onset juvenile MLD, the first problems to be noticed may be behavioral issues. Other features that occur over time include slurred speech, urinary accidents, and seizures. As with infantile MLD, juvenile MLD is a disorder that gets worse over time (progressive). The course of the disease is similar to, but slower than that seen in infantile MLD. Survival for 10-20 years after initial diagnosis is common, and lifespan in some may be longer.

Adult MLD is rare, and is diagnosed in people whose symptoms are noted after 14-16 years of age into the 30s or 40s. Initial symptoms are variable, but include worsening problems with school or work performance and personality changes. Some people may have issue with alcohol/drug use, poor money management, or difficulty managing emotions resulting in psychiatric evaluation and diagnosis of a mental health disorder such as schizophrenia. Other features such as bewilderment, inappropriate response to one's surroundings, paranoia, dementia and hearing things/voices (auditory hallucinations) are possible. Other people may have neurologic findings including seizures or weakness, clumsiness, and loss of coordination resulting in a diagnosis of neurodegenerative disease or multiple sclerosis. Some people may experience a peripheral neuropathy as a part of their MLD. In a smaller percentage, an isolated peripheral neuropathy may be the presenting symptom.

People with adult onset MLD may have periods during which they are stable, followed by times with decline, inappropriate behavior, and poor decision-making. These periods can become very challenging for family and care givers. People with adult-onset MLD will eventually develop movement disorders and/or difficulty using their muscles, which results in them needing help with activities of daily living (eating, getting dressed, urination, etc). Other features might include severe joint limitation or seizures that occur and may resolve. Eventually, the ability to communicate effectively is lost, though a person with adult onset MLD does not usually stop interacting with his/her surroundings until late in the disease. Some can have adult-onset MLD for as long as 20 or 30 years during which time there will be progession of symptoms. In the final stage of the condition, the individual is blind, bedridden, and unresponsive. Cause of death is usually pneumonia or another infection.

SOURCE: Emory University - Department of Human Genetics in collaboration with ThinkGenetic • • DATE UPDATED: 2016-06-25


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