Arylsulfatase A pseudodeficiency: a common polymorphism which is associated with a unique haplotype.

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.