Detection of Fabry's disease heterozygotes by hair root analysis

Abstract

The alpha-galactosidase/beta-hexosaminidase ratio was measured for individual hair roots as a method for heterozygote detection in Fabry's disease. Hair root analysis in control individuals revealed no striking sex difference in alpha-galactosidase/beta-hexosaminidase ratio when five males and five females were compared. The values for the ratio X 100, calculating both enzyme activities in nmol of product per min per microliter of hair extract, ranged from 0.8 to 9 for controls and from less than 0.1 to 0.4 for two hemizygous males. Hair root analysis in four heterozygotes with clinical evidence of disease gave values for each individual in the control range, in the range for hemizygotes and in an intermediate range. The experience using hair root analysis for heterozygote detection in the X-linked Lesch-Nyhan syndrome suggests that this approch will be a sensitive heterozygote detection method which takes advantage of the occurrence of hairs with a deficient phenotype on the basis of Lyonization. We observed an affected male who was born to a female without clinical or biochemical evidence (examination included extensive hair root analysis) of Fabry's disease, thus documenting a likely instance of new mutation.