Based on the age of onset, different types of metachromatic leukodystrophy (MLD) can be distinguished. The types are roughly associated with clinical manifestations and disease progression. But, on an individual level, it is difficult to predict the MLD progression. A summary of symptoms and characteristics is shown below.

What are the types of MLD?

● Late-infantile MLD (onset before the age of 2,5 years)

● Juvenile MLD (onset between 2,5 – 16 years of age)

● Adult MLD (onset after the age of 16 years)

What are the symptoms of MLD?

● Developmental delay, stagnation, or deterioration.

● Loss of developmental milestones or failure to achieve developmental milestones, such as walking, crawling, and talking.

● Motor clumsiness

● Motor weakness

● Spasticity

● Tremor (e.g. shaking hands)

● Behavioral problems (irritable, aggressive, and disinhibited behavior)

● Cognitive decline (learning problems, decline in school performance)

● Suddenly occurring strabismus

● Epilepsy

● Gall bladder problems (pain in the right upper abdomen)

● Micturition problems (incontinence, urinary retention)

● Defecation problems (incontinence, constipation)

● Psychiatric symptoms (personality changes, behavioral changes, psychotic symptoms, frontal syndrome, mood disorders, ADHD or autism)

What are the characteristics of metachromatic leukodystrophy?

What are the characteristics of late-infantile MLD?

Classically, a child develops normally during the first year of life. In the following period, the development initially stagnates and then deteriorates. The child loses milestones, such as walking, crawling, or sitting without support. The motor symptoms are often the most prominent. The disease progresses quite quickly. Eventually, they completely lose contact with the environment. Most children die between 2 and 7 years after the onset of the first symptoms.

What are the characteristics of juvenile MLD?

Early-juvenile (onset between 2,5 – 6 years of age) and late-juvenile (onset between 6 – 16 years) can be distinguished. The nature of the symptoms varies a lot. Often the clinical picture is a combination of motor regression, behavioral changes, and deterioration in school performance. The disease progresses slower compared to late-infantile MLD. When untreated life expectancy varies from 3 to 15 years after the onset of symptoms depending of intercurrent complications.

What are the characteristics of adult MLD?

This is the least frequent and least well described type of MLD. It is an insidious disease. It is characterized by psychological or psychiatric symptoms. For example loss of initiative, disinhibition, and inappropriate behavior. In addition, cognitive decline is present that is often unnoticed for a long period. Extensive irreversible damage to the brain is often already present at the time of diagnosis. Ultimately, also adult patients lose all physical and mental skills. The patient will become completely dependent on care. Life expectancy varies from 5 to 35 years after the onset of first symptoms. When treated with a causal therapy, life expectancy might be longer.

Sometimes treatment for MLD is possible. Treatments can influence disease progression and life expectancy. You can read more about therapies for MLD here.