[Fragility of the X chromosome and inhibition of dihydrofolate reductase. Comparison of the effects of 2 antibiotics: trimethoprim and pyrimethamine]

Abstract

The increase in frequency of the Xq27 gap is investigated after addition to the culture medium of two inhibitors of dihydrofolate reductase : trimethoprim (TMP) and pyrimethamine (PMT). Neither antibiotic induced the gap in ten normal subjects. In five Xqfra, mentally retarded, untreated boys, TMP (26,7 mg/l) and PMT (1,25 mg/l) increased equally the gap frequency. In two out of four women carrying the Xqfra and in three out of four Xfra mentally retarded boys, treated for a few months, with oral folic acid (one milligram/kg/day), TMP increased the frequency of the gap, while PMT was practically inactive. PMT is a much more powerful inhibitor of dihydrofolate reductase than TMP : it was concluded therefore that TMP could also act on some other steps of the monocarbons' metabolism. The only patient who reacted strongly to both TMP and PMT had previously suffered a severe neurologic regression during an antibiotherapy with TMP. It is stressed that dihydrofolate reductase inhibitors should be avoided when treating Xqfra patients.