Detection of Fabry's disease heterozygotes by hair root analysis

Abstract

The α‐galactosidase/β‐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 α‐galactosidase/β‐hexosaminidase ratio when five males and five females were compared. The values for the ratio × 100, calculating both enzyme activities in nmol of product per min per ×l of hair extract, ranged from 0.8 to 9 for controls and from <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 approach 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.

Sporadic occurrence of Duchenne Muscular Dystrophy: evidence for new mutation

“…The study of cells of clonal origin in the suspected female carrier improves detection made difficult by random inactivation of the X-chromosome (Lyon 1961). These techniques have been applied to other X-linked recessive disorders such as testicular feminization (Meyer et al 1975) and Fabry's disease (Beaudet & Caskey 1978). The serum CPK is presently the best available method for DMD carrier detection.…”

“…New mutations in humans are known to account for occurrence of sporadic cases of achondroplasia, Marfan's disease (Vogel 1977), Fabry's disease (Beaudet & Caskey 1978), Lesch-Nyhan syndrome (Franke el ah 1976), and hemophilia A (Ratnoff & Jones 1977). In the case of achondroplasia and Marfan's disease, the fathers of sporadic cases were older on the average by several years (Vogel 1977), suggesting the sperm rather than the ovum was a more likely source of the new mutation.…”

Pseudodeficiency of α‐galactosidase A

“…Testing for heterozygosity in Xlinked inherited diseases always poses problems because of Lyonization. The assay of enzyme levels in hair roots has been shown to be useful in carrier detection of these diseases such as Fabry disease (Beaudet & Caskey 1978) used successfully when testing the two daughters for heterozygosity for this mutation. Figure 1 clearly demonstrates the presence of two hair follicle populations in both daughters, one with approximately normal values and one that is deficient in a-galactosidase activity.…”

Heterozygote detection in glucose‐6‐phosphate dehydrogenase deficiency: limitation of hair follicle analysis

“…Methods using hair roots have been described for the detection of females heterozygous for X-linked inherited enzyme defects, such as deficiency of hypoxanthineguanine phosphoribosyl transferase (Gartler et al 1971, Francke et al 1973, de Bruyn et al 1974), a-galactosidase (Grimm et al 1976, Beaudet & Caskey 1978, Vermorken et al 1978) and glucose-6-phosphate dehydrogenase (Romeo et al 1976, Vermorken et al 1979). These methods seem to give reliable results.…”