PRACTICAL SUGGESTIONS IN DIAGNOSING METACHROMATIC LEUKODYSTROPHY IN PROBANDS AND IN TESTING FAMILY MEMBERS

Metachromatic leukodystrophy (MLD) is one of the most severe genetical ly determined demyelination diseases. It is caused by a deficit in the activity of sulfatide sulfatase. The diagnosis is made by demonstrati ng a deficiency of arylsulfatase A (ASA) activity in leukocytes or cul tured skin fibroblasts. Diagnosis based only on the activity of ASA is complicated by the fact that there exists a condition of ASA pseudode ficiency (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 er roneous diagnosis on the basis of only ASA activity. Nonetheless, it s eems necessary to develop a reliable and simple diagnostic procedure s o as to enable diagnosis and genetic counseling for carriers. We prese nt two diagnostic flow charts entailing determination of ASA activity, identification of the pseudodeficit mutation and detection of sulfati des in a 24-hour urine collection.