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.