Żółkowska Joanna, Hozyasz Kamil K, Nowacka Maria
Klinika Pediatrii, Instytut Matki i Dziecka, Warszawa, Polska, Przykliniczna Poradnia Fenyloketonurii, Instytut Matki i Dziecka, Warszawa, Polska.
Klinika Pediatrii, Instytut Matki i Dziecka, Warszawa, Polska.
Dev Period Med. 2017;21(4):344-360. doi: 10.34763/devperiodmed.20172104.344360.
Phenylketonuria (PKU) is the autosomal recessive deficiency of phenylalanine hydroxylase resulting in the accumulation of phenylalanine (Phe) in blood and in the brain. Phe restriction in a patient's diet is determined depending on the amount of Phe intake which allows for stable blood Phe levels within the therapeutic range of 120-360µmol/L. In clinical practice the empirical determination of Phe tolerance relies on frequent assessment of blood Phe concentrations in relation to Phe intake from food records. Untreated maternal PKU may lead to maternal PKU syndrome in offspring. The objective of the study was to compare Phe tolerance during the course of singleton and multiple pregnancies of PKU patients. Case subjects and methods: The cases reviewed included three sets of classical PKU-affected Polish women on a low-phenylalanine diet during the course of singleton and twin pregnancies and their PKU-unaffected newborns. All the patients were under regular supervision of a metabolic dietitian to stabilize blood Phe levels and determine Phe tolerance. Data on pregnancy weight gain, the gestational age when the diet initiated, the percent of Phe assessments < 120 µmol/L and > 360 µmol/L, as well as offspring birth measurements were analyzed.
The total increase in Phe tolerance and its pattern during the course of singleton and twin pregnancies differed remarkably in each patient. Three PKU women (Q383X/R408W, EX3DEL/EX3DEL, R281L/R408W) increased their Phe tolerance in singleton and twin pregnancies by 579%/468%, 674%/261%, and 427%/236%, respectively. During the last 10 weeks of singleton and twin pregnancy Phe tolerance showed an increase by 62%/149%, 33%/64%, and 37%/40%, respectively. The analysis of predictors for Phe tolerance showed that an individual's weight gain and the fetal weight gain as estimated from liveborn birth-weight data had no predictive capacity.
Individual Phe tolerance in singleton pregnancies of PKU patients does not predict tolerance in twin pregnancy. Further research on the growing population of multiple pregnancy PKU patients is necessary to provide evidence-based guidelines to optimize the treatment of PKU in females of childbearing age.
苯丙酮尿症（PKU）是一种常染色体隐性疾病，因苯丙氨酸羟化酶缺乏，导致血液和大脑中苯丙氨酸（Phe）蓄积。根据苯丙氨酸摄入量来确定患者饮食中苯丙氨酸的限制量，以使血液中苯丙氨酸水平稳定在120 - 360µmol/L的治疗范围内。在临床实践中，苯丙氨酸耐受性的经验性确定依赖于根据食物记录中苯丙氨酸摄入量，频繁评估血液中苯丙氨酸浓度。未经治疗的母体苯丙酮尿症可能导致后代出现母体苯丙酮尿症综合征。本研究的目的是比较苯丙酮尿症患者单胎和多胎妊娠期间的苯丙氨酸耐受性。病例对象与方法：回顾的病例包括三组患典型苯丙酮尿症的波兰女性，她们在单胎和双胎妊娠期间接受低苯丙氨酸饮食，并生育了未患苯丙酮尿症的新生儿。所有患者均在代谢营养师的定期监督下，以稳定血液中苯丙氨酸水平并确定苯丙氨酸耐受性。分析了妊娠体重增加、开始饮食时的孕周、苯丙氨酸评估值<120µmol/L和>360µmol/L的百分比以及后代出生测量数据。
每位患者单胎和双胎妊娠期间苯丙氨酸耐受性的总体增加及其模式差异显著。三名苯丙酮尿症女性（Q383X/R408W、EX3DEL/EX3DEL、R281L/R408W）在单胎和双胎妊娠期间的苯丙氨酸耐受性分别增加了579%/468%、674%/261%和427%/236%。在单胎和双胎妊娠的最后10周，苯丙氨酸耐受性分别增加了62%/149%、33%/64%和37%/40%。苯丙氨酸耐受性预测因素分析表明，根据活产出生体重数据估算的个体体重增加和胎儿体重增加没有预测能力。
苯丙酮尿症患者单胎妊娠期间的个体苯丙氨酸耐受性不能预测双胎妊娠期间的耐受性。有必要对越来越多的多胎妊娠苯丙酮尿症患者进行进一步研究，以提供基于证据的指南，优化育龄期女性苯丙酮尿症的治疗。
