Practical suggestions in diagnosing metachromatic leukodystrophy in probands and in testing family members

Metachromatic leukodystrophy (MLD) is one of the most severe genetically determined demyelination diseases. It is caused by a deficit in the activity of sulfatide sulfatase. The diagnosis is made by demonstrating a deficiency of arylsulfatase A (ASA) activity in leukocytes or cultured skin fibroblasts. Diagnosis based only on the activity of ASA is complicated by the fact that there exists a condition of ASA pseudodeficiency (Pd). Due to the relatively high risk of the MLD/Pd and MLDPd/Pd genotypes among families of patients, it is possible to make an erroneous diagnosis on the basis of only ASA activity. Nonetheless, it seems necessary to develop a reliable and simple diagnostic procedure so as to enable diagnosis and genetic counseling for carriers. We present two diagnostic flow charts entailing determination of ASA activity, identification of the pseudodeficit mutation and detection of sulfatides in a 24-hour urine collection.