Detection of heterozygous carriers for phenylketonuria by a l-[2H5]phenylalanine stable isotope loading test

Significant phenylalanine hydroxylation in vivo in patients with classical phenylketonuria.

“…Results were compared with those in six normal adults (mean age 36 yr, range 25-49, five males, one female) who have been described previously (22). All had fasting plasma phenylalanine/tyrosine concentration ratios of less than 1, making carrier status for PKU unlikely (13). Dietary intake of phenylalanine was assessed at the time of study by recall dietary history or, where history was uncertain, by 3-d diet diary.…”

“…Measurement of phenylalanine hydroxylase activity in liver has allowed discrimination of some phenotypes (3)(4)(5), but the invasiveness of liver biopsy precludes the technique from routine use. Consequently, a number of in vivo methods have been investigated (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). These techniques have, in general, attempted to assess the ability to clear phenylalanine from plasma or to hydroxylate it to tyrosine.…”

“…A number of studies have examined the response in plasma phenylalanine and/or tyrosine following an oral or intravenous load of phenylalanine (8,11,12,(16)(17)(18), but these tests fail to discriminate between normal and heterozygote subjects in a substantial number of cases. Better discrimination has more recently been obtained by various deuterated phenylalanine loading techniques (7,13,19). Estimates of in vivo enzyme activity using these methods suggest that PKU carriers have -50% of normal in vivo phenylalanine hydroxylase activity, subjects with hyperphenylalaninemia (HPA, a mild PKU variant) have -10% ofnormal activity, and subjects with classical PKU have between 0.3 and 3% of normal activity.…”

Aspartame loading test in PKU heterozygous individuals bearing severe and moderate mutations

“…Mental retardation is the main symptom observed in non‐treated PKU patients [3]. Several methods have been developed for the detection of PKU heterozygous individuals, based on measurements of plasma phenylalanine (Phe) and tyrosine (Tyr) levels or analysis of the Phe/Tyr and Phe 2 /Tyr ratios [4,5]. However, results obtained in most of these studies showed an important overlap among heterozygous and normal individuals.…”

Phenylalanine and Tyrosine Metabolism Analysis in Heterozygotes for Phenylketonuria and in Healthy Individuals

“…The majority of the employed methods to distinguish PKU heterozygotes from healthy individuals are based on evaluation of blood levels of Phe and Tyr after an oral, 9-11 intravenous 12 Phe overload or deuterium-labeled administration. 13 In this concern notwithstanding the analyses of a single parameter (Phe) may not correctly distinguish both the groups.…”