Molecular biology of G 6 PD variants

Glucose-6-phosphate dehydrogenase (G6PD, E.C. 1.1.1.49) deficiency is probably the most common disease-producing enzyme deficiency of man. Originally described in the 1950's in Black Americans and regarded a single disorder, it soon became apparent that this enzyme defect occurred in many populations and that it was biochemically heterogeneous. By 1965 a considerable number of distinct variants had been described and a WHO Scientific Group was convened to standardize methods of characterization of variants, so as to allow meaningful interlaboratory comparisons to be made. In the succeeding quarter of a century nearly 400 variants believed to be unique have been characterized, most of them by the standard methods that had been adopted in 1967. Helpful as standardization proved to be, however, comparison of variants with one another proved to be difficult. Electrophoretic mobilities and kinetic constants vary with changes in reagents over which investigators have no control, and the lack of stability of enzymes and their kinetic characteristics makes side-by-side comparison a goal that can be achieved only rarely. It is not surprising, then, that in at least one instance variants that appeared to be quite different proved to have been obtained from two members of the same family, and were undoubtedly identical. It has thus been clear for many years that a true appreciation of the extent of G6PD mutations would require the acquisition of incontrovertible structural data.(ABSTRACT TRUNCATED AT 250 WORDS)