A closer look at ARSA activity in a patient with metachromatic leukodystrophy

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease.
• It is primarily caused by a deficiency in arylsulfatase A (ARSA) activity.
• The late infantile form typically presents with motor skill regression, dysphagia, seizures, and hypotonia.

Observation:

• A 4-year-old female presented with rapid developmental regression, motor milestone loss, spasticity, and dysphagia.
• MRI revealed significant white matter abnormalities and volume loss.
• Initial ARSA enzymatic testing was within the normal range.

Findings:

• Urine sulfatide excretion was significantly elevated in a second laboratory.
• ARSA activity was partially decreased under standard conditions (37% of normal mean).
• ARSA activity dropped to <10% of controls when substrate concentration was lowered, indicating a specific enzyme defect.
• Genetic analysis revealed homozygosity for a novel missense mutation in the ARSA gene.

Implications:

• This case underscores the diagnostic challenges in MLD when standard biochemical tests yield ambiguous results.
• It emphasizes the critical role of detailed biochemical assays and molecular genetic testing for accurate MLD diagnosis.
• Proper diagnosis is crucial for understanding disease progression and potential management strategies.