Effects of oral contraceptives and obesity on carrier tests for phenylketonuria

Abstract

Carriers of phenylketonuria have previously been detected by tests based on fasting levels of plasma phenylalanine and tyrosine or on the height and shape of the tolerance curve after a phenylalanine load. Compared with controls, carriers have higher plasma phenylalanine levels and lower tyrosine levels. Plasma tyrosine levels in women vary with hormonal changes so that plasma tyrosine levels and plasma phenylalanine-tyrosine ratios are not very reliable as tests for female heterozygotes of phenylketonuria. Plasma phenylalanine levels after an oral phenylalanine load were the same in controls and in women taking oral contraceptives. This indicates that there is no significant change in phenylalanine metabolism, and the decrease in plasma tyrosine could therefore be due to increased metabolism of the tyrosine. When the amount of the phenylalanine load is based on weight (100 mg/kg), there is a positive correlation between the plasma phenylalanine levels and degree of obesity as measured by Rohrer's ponderal index Wt(g) × 100/Ht(cm) 3. In most studies carriers have been older and heavier than controls, suggesting that many of the tests may have distinguished between carriers and controls largely on the basis of degree of obesity. The validity of some of the tests for carriers of phenylketonuria is therefore in doubt.