Effect of Storage on Phenylalanine and Tyrosine Measurements in Whole-Blood Samples

Abstract

With an incidence of 1 in 6600 newborns, phenylketonuria (PKU) is among the most common inborn errors of metabolism. PKU is caused by a deficiency of hepatic phenylalanine hydroxylase (1). The increase in the blood Phe concentration leads to permanent structural damage of the central nervous system as a result of disturbed myelination and neurotransmitter deficiency (2). If plasma Phe concentrations are normalized by a low-protein diet with supplementation of essential amino acids before 3 weeks of age, irreversible mental retardation is prevented (2). Still, strict metabolic control is mandatory throughout childhood (2) and perhaps into adult life (3). This is achieved by regular measurement of blood Phe and Tyr concentrations. Tyr is monitored because Phe hydroxylase deficiency renders it an essential amino acid in PKU. Recommendations for the duration and intensity of dietary control are not uniform (2); likewise, there is some variation in the local practices of PKU monitoring. The current guidelines of the German “Arbeitsgemeinschaft fur Padiatrische Stoffwechselerkrankungen” (The German Working Group for Metabolic Diseases) set a target range for Phe concentrations of 40–250 μmol/L, at least until age 10 (≤900 μmol/L is acceptable during adolescence) (4). These recommendations were based on data from samples that were analyzed immediately after sampling (Udo Wendel, University Children’s Hospital, Dusseldorf, Germany, personal communication). Pregnant women with even mild hyperphenylalaninemia also require strict dietary control of Phe concentrations to prevent PKU-induced fetopathy (1). To ensure optimal metabolic control, patients are monitored in specialized clinics where dietary …