Symptoms
Symptoms vary depending on the type of MLD (late infantile, juvenile, or adult) but generally include:
Late Infantile MLD (most common and severe): Muscle weakness, stiffness, difficulty walking, loss of motor skills, developmental delays, irritability, vision problems, seizures, and progressive loss of cognitive function.
Juvenile MLD: Behavioral problems, declining school performance, gait disturbances, muscle weakness, speech difficulties, and cognitive decline.
Adult MLD: Psychiatric symptoms (depression, psychosis), cognitive decline, gait abnormalities, muscle weakness, bladder and bowel control issues.
Causes
MLD is caused by mutations in the ARSA gene, which provides instructions for making the arylsulfatase A enzyme. These mutations result in a deficiency or absence of functional ARSA, causing sulfatides to accumulate in the brain, spinal cord, and other organs. It is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
There is currently no cure for MLD. Treatment focuses on managing symptoms and providing supportive care.
Symptom Management: Medications can be used to manage seizures, pain, spasticity, and behavioral problems.
Physical and Occupational Therapy: To maintain mobility and function for as long as possible.
Enzyme Replacement Therapy (ERT): Enzyme replacement therapy (ERT) with atidarsagene autotemcel is an approved treatment for pre-symptomatic late infantile, pre-symptomatic early juvenile and early symptomatic early juvenile.
Hematopoietic Stem Cell Transplantation (HSCT): In some cases, HSCT may slow the progression of the disease, particularly when performed early in the disease course.
Is Communicable
MLD is not communicable. It is a genetic disorder caused by inherited gene mutations and cannot be spread from person to person.
Precautions
Since MLD is a genetic disorder, precautions involve genetic counseling and testing for individuals with a family history of the disease. Carrier testing can determine if individuals are carriers of the mutated ARSA gene, and prenatal testing can be performed to diagnose MLD in a fetus. Other precautions focus on managing the symptoms and preventing complications associated with the disease, such as falls, infections, and aspiration pneumonia.
How long does an outbreak last?
MLD is not an infectious disease and does not have outbreaks. It is a chronic, progressive condition that lasts a lifetime. The rate of progression varies depending on the type of MLD and individual factors.
How is it diagnosed?
Diagnosis of MLD typically involves:
Enzyme Assay: Measuring ARSA enzyme activity in blood, skin fibroblasts, or leukocytes (white blood cells). Low ARSA activity is indicative of MLD.
Sulfatide Measurement: Measuring sulfatide levels in urine. Elevated sulfatide levels support the diagnosis.
Genetic Testing: Analyzing the ARSA gene for mutations confirms the diagnosis.
MRI of the Brain: Magnetic Resonance Imaging (MRI) shows characteristic patterns of white matter changes in the brain.
Nerve Conduction Studies: Assessing the function of peripheral nerves.
Timeline of Symptoms
The timeline of symptoms varies greatly depending on the specific form of MLD:
Late Infantile MLD: Symptoms typically appear between 6 months and 2 years of age. Rapid progression with loss of motor skills, cognitive decline, and eventual loss of function within a few years.
Juvenile MLD: Symptoms usually begin between 3 and 10 years of age. Slower progression compared to the late infantile form, with a gradual decline in motor, cognitive, and behavioral functions over several years.
Adult MLD: Symptoms may emerge from the teenage years into adulthood (16+). Often, symptoms are more subtle and progress slowly over many years. Psychiatric symptoms may precede neurological signs.
Important Considerations
Genetic Counseling: Essential for families with a history of MLD to understand the inheritance pattern and recurrence risk.
Early Diagnosis: Early diagnosis is crucial for access to potential therapies like hematopoietic stem cell transplantation or enzyme replacement therapy (if applicable) that may slow disease progression.
Supportive Care: Comprehensive supportive care is vital to manage symptoms and improve the quality of life for affected individuals and their families. This includes physical therapy, occupational therapy, speech therapy, and palliative care.
Research: Ongoing research aims to develop more effective treatments and potentially a cure for MLD.