Abnormal Phenylalanine Loading Tests in Mothers of Children with Cleft Defects

Abstract

The genetic endowment, the nutritional status, and the reaction to stress in the mother have all been proposed as separate etiological factors in producing clefts. The interaction of these factors on the developing fetus is itself probably the relevant factor. However, no biochemical differences to support this thesis have been previously demonstrated in women who produce affected children. The purpose of this study was to investigate the absorption of phenyl-alanine by women who had borne children with cleft defects. The amino acid phenylalanine was chosen because of the consistency of excretion of phenolic acids, metabolic end products of this amino acid, in the urine of the women in question, especially p-hydroxyphenylacetic acid. These findings were reported earlier (7). Figure 1 shows the metabolic pathway from the phenylalanine t0 the phenolic acids. Methods Water solutions of L-phenylalanine and L—tyrosine, in the concentra— tion of 0.1 g/kg, were given on different days to the subjects after they were on overnight fast. Samples of blood and urine were taken at 0, 1, 2, and 4 hours. The blood levels of phenylalanine and tyrosine were determined fiuorometri-cally by the methods of McCaman and Robins (4) and Waalkes and Udenfriend (8), respectively. Women with no defective children were used as controls. They were chosen to match as closely as possible the age of the mothers of cleft defect children (hereafter abbreviated as MCD).