Atypical metachromatic leukodystrophy? Problems with the biochemical diagnosis

Area of Science:

• Biochemistry
• Genetics
• Metabolic Disorders

Background:

• Arylsulfatase A (ASA) deficiency causes metachromatic leukodystrophy.
• A rare variant of ASA deficiency presents with low enzyme activity but normal neurological function.
• Prenatal diagnosis is crucial for genetic counseling in affected families.

Observation:

• A patient exhibited marked deficiency in arylsulfatase A (ASA) activity and impaired sulfatide degradation.
• Pathological sulfatide excretion was detected in the patient's urine.
• Clinically unaffected family members also showed low ASA activity and impaired sulfatide metabolism in fibroblasts.

Findings:

• The sulfatide-loading test demonstrated impaired sulfatide degradation in fibroblasts from the affected patient and his family members.
• Despite low arylsulfatase A (ASA) activity, neurological assessments were normal in the patient and his relatives.
• Fibroblasts from clinically normal relatives accumulated sulfatides, indicating a metabolic abnormality.

Implications:

• The sulfatide-loading test is not a reliable method to differentiate between pseudoarylsulfatase A deficiency and this unusual ASA deficiency variant.
• Prenatal diagnosis for this specific ASA deficiency variant requires alternative diagnostic approaches.
• Further research is needed to identify reliable markers for prenatal diagnosis of this rare metabolic disorder.