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The allele for pseudodeficiency (PD) of the lysosomal enzyme arylsulfatase A (ARSA) is a common polymorphism in all populations. The PD allele frequency in different Israeli ethnic groups was found to range from 9.2-22.7%. The PD allele includes two different mutations PD(1) and PD(2) in an approximately 1 Kb interval. In this study we confirmed that while PD(1) may be found alone as a polymorphism, PD(2) is always associated with the PD allele (660 alleles screened). Analysis of three ARSA intragenic polymorphisms showed a complete linkage disequilibrium between the PD allele and an haplotype defined by the three polymorphic restriction sites. The results suggest that the origin of the PD polymorphism may be a common founder, or recurrent mutations which are occurring in a unique haplotype.

Lysosomal storage diseases (LSD) are a group of more than 40 disorders, many of them with overlapping phenotype, in which clinical diagnosis is often difficult. Definitive diagnosis is based on enzyme assays, a large number of such assays usually being necessary during the investigation of each patient. In addition, there will frequently be a need for tissue culture in order to provide enough material for analysis. Taking into account these difficulties, we designed a flowchart for the detection of LSD that is based on 2 sets of tests requiring only random urine and heparinized blood. Here we describe this routine and report the results of its application to 105 Brazilian patients in whom a LSD was suspected. We think that the application of this rationale represents a saving of work and costs, and should be of special interest to genetic centers in developing countries.