Diversity of phenylalanine tolerance in pregnant phenylketonuria patients homozygous for the p.R408W mutation: the need for improved understanding of phenylalanine homeostasis

Abstract

Dietetic treatment of phenylketonuria (PKU) includes a low-phenylalanine (phe) diet that provides sufficient phe for maintenance and growth plus special phe-free formulas with amino acids to meet requirements for protein, energy and micronutrients.Dietetic treatment of phenylketonuria (PKU) includes a low-phenylalanine (phe) diet that providessufficient phe for maintenance and growth plus special phe-free formulas with amino acids to meetrequirements for protein, energy and micronutrients. Rules for predicting phenylalanine tolerancechanges during the course of pregnancy are not clear. The purpose of this report is to describe phetolerance in pregnant PKU patients with the PAH genotype p.R408W/p.R408W. Low-phe diet wasstarted before the pregnancies. The reviewed cases included three PKU women with two pregnanciesand four PKU women with one pregnancy. Phe restriction in a patient’s diet was determined upon theamount of this amino acid intake, which allows for stable blood phe concentrations within the targetrange of 120–360μmol/L. Daily phe tolerance increased from 344±85mg in the pre-conceptional periodup to 1348±466mg at the end of the third trimester. Before delivery, the lowest and highest phe toleranceexpressed per kg of the pregnant women’s body weight were 6.8 mg and 26.9 mg respectively. Phetolerance varies greatly even between pregnancies of patients with the same PKU genotype. Furtherresearch on pregnant PKU patients is essential to identify biological regulators of phe tolerance duringpregnancy and provide evidence-based guidelines to optimise the dietetic care.