| Download the amazing global Makindo app: ✅ Means NICE/National Guidelines 2026 compliant Android | Apple | |
|---|---|
| MEDICAL DISCLAIMER: Educational use only. Not for diagnosis or management. See below for full disclaimer. |
Metachromic leukodystrophy
🧬 Metachromatic Leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder. It results from a deficiency of the enzyme arylsulfatase A, causing toxic accumulation of sulfatides. This leads to progressive demyelination of the central and peripheral nervous systems.
📖 About
- Also called Arylsulfatase A deficiency.
- Sulfatide accumulation damages oligodendrocytes (CNS) and Schwann cells (PNS), leading to widespread white matter loss.
- Named "metachromatic" because accumulated sulfatides stain a different (meta-) colour with certain dyes 🔬.
🧬 Aetiology
- Mutations in the ARSA gene (chromosome 22q13) → ↓ Arylsulfatase A activity.
- Rarely due to mutations in PSAP gene (encodes saposin B, a cofactor).
- Inheritance: Autosomal recessive.
🧒 Clinical Features
- Onset types:
- 👶 Late-infantile (most common, severe):
- Onset at 1–2 years with motor regression, gait disturbance, hypotonia → spasticity
- Optic atrophy → blindness
- Seizures, peripheral neuropathy, developmental arrest
- Death usually within first decade
- 🧒 Juvenile form:
- Onset 4–12 years
- School difficulties, behavioural changes
- Progressive motor dysfunction, seizures
- 🧑 Adult form:
- Psychiatric features (depression, psychosis, personality change)
- Dementia, peripheral neuropathy
- Slower progression, survival into adulthood
- 👶 Late-infantile (most common, severe):
🔬 Investigations
- 🧪 Arylsulfatase A enzyme assay: Low activity in leukocytes or fibroblasts (diagnostic).
- 🧬 Genetic testing: Confirms ARSA mutations; allows carrier & prenatal diagnosis.
- 💧 Urinary sulfatides: Elevated levels.
- 🧫 Histology: Metachromatic deposits in nerve biopsies with toluidine blue staining.
- 🧠 MRI brain: Symmetrical periventricular white matter changes (tigroid pattern of demyelination).
🩹 Management
- 💊 Supportive care: Anti-seizure drugs, physiotherapy, speech and occupational therapy.
- 🧵 Bone marrow / stem cell transplantation: May slow progression if done early in juvenile/adult forms.
- 🧬 Gene therapy: Experimental; early trials show promise for long-term correction.
- 💉 Enzyme replacement therapy (ERT): Recombinant arylsulfatase A in development.
- 🌱 Palliative care: For advanced disease, focus on comfort and quality of life.
📊 Prognosis
- Late-infantile: Rapid progression, death in childhood.
- Juvenile: Slower but still progressive, survival into adolescence/young adulthood.
- Adult: Variable, may live decades with psychiatric/neurodegenerative course.
📚 References
- NORD – Metachromatic Leukodystrophy
- Gieselmann V. Metachromatic Leukodystrophy. In: Adam MP et al., GeneReviews, 2019.