Critical issues for the proper diagnosis of Metachromatic Leukodystrophy

• Diagnosis is relevant in pre-symptomatic MLD patients to be eligible for therapeutic treatments.
• Standard enzymatic determination of ARSA activity is not always informative for MLD diagnosis.
• A combination of thorough biochemical and molecular analyses allows for correct diagnosis of MLD.

Metachromatic Leukodystrophy is a lysosomal storage disorder caused by Arylsulfatase A deficiency. Diagnosis is usually performed by measurement of enzymatic activity and/or characterization of the gene mutations. Here we describe a family case in which the determination of enzyme activity alone did not allow diagnosis of the pre-symptomatic sibling of the index case. Only combination of gene sequencing with thorough biochemical analysis allowed the correct diagnosis of the sibling, who was promptly directed to treatment.