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# Metachromatic leukodystrophy

In metachromatic leukodystrophy sulfatides build up in myelin; a child, young person or adult loses walking, strength and later mental abilities.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [White matter](https://durgical.com/en/anatomy/white-matter-of-telencephalon/)
- [Corpus callosum](https://durgical.com/en/anatomy/corpus-callosum/)
- [Gallbladder](https://durgical.com/en/anatomy/gallbladder/)
- [Sciatic nerve](https://durgical.com/en/anatomy/sciatic-nerve/)

## In biochemistry

- [Sphingolipids and sphingolipidoses](https://durgical.com/en/biochemistry/topics/sphingolipids-and-sphingolipidoses/)
- [Lysosomal storage diseases](https://durgical.com/en/biochemistry/topics/lysosomal-storage-diseases/)
- [Galactosylceramide (galactocerebroside)](https://durgical.com/en/biochemistry/molecules/galactosylceramide/)
- [Sulfatide](https://durgical.com/en/biochemistry/molecules/sulfatide/)
- [Arylsulfatase A (ARSA)](https://durgical.com/en/biochemistry/enzymes/arylsulfatase-a/)

## In histology

- [Glial cells: astrocytes, oligodendrocytes, microglia, Schwann cells](https://durgical.com/en/histology/glial-cells-astrocytes-oligodendrocytes-microglia-schwann-cells/)

## What it is

An autosomal recessive lysosomal leukodystrophy caused by deficiency of arylsulfatase A (ARSA gene) or, rarely, its activator saposin B (PSAP gene); sulfatides accumulate in central and peripheral myelin.

## Who gets it

Reported in 1 in 40,000 to 160,000 people worldwide, with much higher frequencies in some isolated populations. The late infantile form is the most common.

## Causes

- Biallelic variants of the ARSA gene
- Rarely, PSAP variants with saposin B deficiency

## Risk factors

- Carrier parents or an affected sibling

## Pathophysiology

Arylsulfatase A removes the sulfate from sulfatide in the lysosome. Without it, sulfatides build up in oligodendrocytes and Schwann cells, which can no longer maintain myelin: progressive brain demyelination and peripheral neuropathy follow. Sulfatides are also deposited in [kidney](https://durgical.com/en/anatomy/kidney/) and gallbladder. In tissue, the material stains a colour different from the dye (metachromasia).

## Classification

- Late infantile: onset at 1–2 years, with gait disturbance
- Juvenile: onset at 3–16 years, with school and behaviour problems
- Adult: onset after 16 years, with psychiatric symptoms and cognitive decline

## Symptoms and signs

- Clumsiness and falls in a child who already walked
- Weakness and lost reflexes from neuropathy
- Increasing stiffness and spasticity
- Loss of speech and learned skills
- Poor school performance or behaviour change (juvenile)
- Psychosis, personality change or cognitive decline (adult)

## Red flags

- A child losing the ability to walk
- Seizures
- Young adult with psychiatric symptoms and white matter changes on MRI

## Diagnosis

**Clinical**
Motor regression with upper motor neuron signs and peripheral neuropathy, or cognitive and behavioural decline in young people and adults.

**Tests**
Low arylsulfatase A activity in leukocytes; high urinary sulfatides (separates the disease from pseudodeficiency, which has low enzyme without sulfatiduria); ARSA and PSAP testing; slowed nerve conduction; high cerebrospinal fluid protein.

**Imaging**
Brain MRI with symmetric periventricular [white matter](https://durgical.com/en/anatomy/white-matter-of-telencephalon/) lesions in a "tigroid" pattern that spares the U-fibres; [gallbladder](https://durgical.com/en/anatomy/gallbladder/) ultrasound with wall thickening or polyps.

## Treatment

**Procedure**
Gene therapy with the patient's own haematopoietic stem cells corrected with the ARSA gene, in presymptomatic or very early forms.

**Procedure**
Haematopoietic stem cell transplant in juvenile or adult forms with few symptoms.

**Medical**
Control of seizures, spasticity, pain and psychiatric symptoms.

**Rehabilitation**
Physiotherapy, occupational therapy and nutritional support.

## Complications

- Spastic quadriparesis
- Aspiration pneumonia
- Loss of vision and hearing
- Cholecystitis or gallbladder polyps

## Prognosis

In the late infantile form most children lose walking within a few years and die in childhood. Juvenile and adult forms evolve over years or decades.

## Test yourself

Think of the answer, then tap the question to see it.

## Which enzyme is missing in metachromatic leukodystrophy, and what builds up?

Arylsulfatase A; sulfatides accumulate in myelin.

## How is the disease told apart from arylsulfatase A pseudodeficiency?

The disease has high urinary sulfatides; pseudodeficiency has low enzyme but no sulfatiduria and no symptoms.

## Which abdominal organ is often involved in metachromatic leukodystrophy?

The gallbladder, with wall thickening, polyps or cholecystitis.

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## Related conditions

- [Krabbe disease (globoid cell leukodystrophy)](https://durgical.com/en/conditions/krabbe-disease/)
- [Acute cholecystitis](https://durgical.com/en/conditions/acute-cholecystitis/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Metachromatic leukodystrophy: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/) (MedlinePlus, US National Library of Medicine, 2026); [ARSA gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/arsa/) (MedlinePlus, US National Library of Medicine, 2026); [PSAP gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/psap/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Source: https://durgical.com/en/conditions/metachromatic-leukodystrophy/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/metachromatic-leukodystrophy/