Metachromatic Leukodystrophy (MLD)

Overview

• Rare, inherited disease affecting brain and peripheral nerves.
• Caused by accumulation of sulfatides due to deficiency of arylsulfatase A enzyme.
• Progressive and typically fatal, leading to deterioration of motor and cognitive functions.

Causes

• Genetic Mutation: Problem with ARSA gene responsible for enzyme production.
• Enzyme Deficiency: Leads to sulfatides accumulation, damaging myelin sheath.
• Neurological Impact: Lack of myelin disrupts nerve function, causing decline.

Symptoms

• Age of Onset Variability: Late infantile, juvenile, or adult.
• Common Symptoms:
  • Developmental delays
  • Muscle weakness and stiffness
  • Loss of motor skills (e.g., walking)
  • Cognitive decline and dementia
  • Seizures
  • Vision and hearing loss
  • Incontinence, paralysis
  • Difficulty swallowing
  • Personality and behavioral changes

Diagnosis and Treatment

• Diagnosis: Genetic testing, enzyme activity measurements.
• Treatment: No cure; focus on symptom management and quality of life improvement.
  • Physical and occupational therapy
  • Medications for seizures and complications
• Research: Exploring gene therapy and bone marrow transplantation.

Types of MLD

• Late-infantile MLD: Symptoms in early years, rapid progression, often fatal by age 5.
• Juvenile MLD: Symptoms between 4-16 years, slower progression.
• Adult MLD: Symptoms in adulthood, slowest progression.

Prognosis

• Progressive and ultimately fatal.
• Earlier onset leads to faster disease progression.
• Disease course varies by MLD type and individual.

References: Information compiled from various sources including MedlinePlus, Rare Diseases, Cleveland Clinic, Mayo Clinic, and more.