RESUMEN
PURPOSE: Maternal phenylketonuria (MPKU) requires strict control of phenylalanine (Phe) and supplemental tyrosine (Tyr). Monitoring during pregnancy using dried blood spot (DBS) cards by tandem mass spectrometry (MS/MS) is now standard practice, however there are no Phe and Tyr reference ranges for DBS MS/MS method in healthy pregnant women. METHODS: DBS cards (63-1364 days in storage) from healthy women with singleton pregnancies were analyzed by MS/MS. Three hundred ninety DBS cards from 170 pregnancies (5/1-39/6 weeks' gestation), were tested. RESULTS: Both Phe and Tyr levels declined from the first trimester (Phe: 36.2 +/- 10.6; Tyr 25.7 +/- 9.7 µmol/L) to the second trimester (Phe 33.4+/-9.3; Tyr 21.7+/- 6.7 µmol/L) and remained stable in the third trimester (Phe 32.3 +/- 8.7; Tyr 21.0 +/- 6.6 µmol/L). Phe and Tyr levels declined over time since collection (Phe: 0.004 µmol/L per day; Tyr 0.002 µmol/L). Nomograms by gestational age were created using raw data and data adjusted for time from sample collection. Reference ranges by trimester are provided. CONCLUSIONS: Both Phe and Tyr decline quickly during the first trimester and remain relatively constant over the second and third trimesters. These nomograms will provide a valuable resource for care of MPKU.
Asunto(s)
Fenilalanina/sangre , Fenilcetonuria Materna/sangre , Complicaciones del Embarazo/sangre , Tirosina/sangre , Pruebas con Sangre Seca , Femenino , Humanos , Fenilcetonuria Materna/patología , Embarazo , Complicaciones del Embarazo/patología , Valores de Referencia , Espectrometría de Masas en Tándem , Adulto JovenRESUMEN
Women with hyperphenylalaninemia are at risk of having offspring affected with the maternal phenylketonuria syndrome. Here we analyze the effect of the intervention of a nutritionist on plasma phenylalanine control in Maternal Hyperphenylalaninemia. We analyzed a retrospective cohort of 35 completed pregnancies in 20 women with Maternal Hyperphenylalaninemia who visited the metabolic nutritionist during the pregnancy to achieve metabolic control. Women who promptly achieved metabolic control had lower plasma phenylalanine concentrations for the remainder of the pregnancy when compared to women who did not achieve prompt control, and this difference reached statistical significance. The achievement of plasma phenylalanine concentrations within the desired target range by the time of the second visit to the nutritionist is a strong predictor of the ability to maintain the desired target range of plasma phenylalanine for the remainder of the pregnancy. Furthermore, we demonstrate that phenylalanine tolerance increases significantly by trimester in women with classical and variant hyperphenylalaninemia.
Asunto(s)
Fenilalanina/metabolismo , Fenilcetonuria Materna/metabolismo , Fenilcetonurias/metabolismo , Complicaciones del Embarazo/genética , Adulto , Femenino , Humanos , Fenilcetonuria Materna/patología , Fenilcetonuria Materna/terapia , Fenilcetonurias/patología , Fenilcetonurias/terapia , Embarazo , Complicaciones del Embarazo/patología , Complicaciones del Embarazo/terapia , Estudios RetrospectivosRESUMEN
Prevention of embryopathy due to maternal phenylketonuria is possible thanks to a maternal-specific low-phenylalanine diet, which has to be started before conception and followed during the whole gestation. The setup of this diet implies knowing the recommended dietary allowances for normal pregnant women as well as for women with nutritional deficiencies. Women with phenylketonuria must be considered at risk for nutritional imbalance for two main reasons. First, most adult women with phenylketonuria have been on a vegetarian diet for many years without protein substitutes or medical control. Secondly, the strict diet for pregnant women with phenylketonuria may induce anorexia or nutritional deficits if it is not well tolerated or understood. Protein, iron, calcium, selenium, vitamin B 12 and caloric intakes are the most sensitive parameters. Close cooperation with an experienced medical and dietician team is required.
Asunto(s)
Dieta , Fenilalanina , Fenilcetonuria Materna/terapia , Adulto , Femenino , Humanos , Política Nutricional , Estado Nutricional , Fenilcetonuria Materna/patología , Embarazo , Factores de RiesgoRESUMEN
OBJECTIVE: This work attempts to study the cerebral alterations in rat offspring of hyperphenylalaninemic mothers, as well as the possibility of preventing them by means of administration of dietetic supplements of valine, leucine and isoleucine during the pregnancy. PATIENTS AND METHODS: An experimental study in two consecutive pregnancies of 18 Wistar rats was carried out. The first pregnancy serves as the control group. In the second pregnancy, an experimental hyperphenylalaninemia was provoked by means of injection of phenylalanine and chlorophenylalanine (phenylalanine-hydroxylase inhibitor). In half of the mothers during the second pregnancy the diet was supplemented with branched-chain amino acids. In the offspring rats, a histological cerebral study was performed (conventional electron microscopy and study of synaptosomes). A behavioral study (T-water maze) was also performed at birth and on the 35th and 65th days of life. RESULTS: The offspring of the group submitted to hyperphenylalaninemia were microcephalic (p = 0.0003) and had fewer synaptosomes that had a larger surface area (p = 0.0081 in newborn rats, p = 0.0028 on the 35th day of life) and of a more immature aspect (less vesicular content). In addition, alteration in the myelinization were detected. In the behavior test (65th day of life), the offspring of the mothers with hyperphenylalaninemia make significantly more mistakes (p = 0.0167) and they needed more time for their resolution (p = 0.059). None of these alterations could be prevented by the administration of supplements of branched-chain amino acids to the mother. These supplements resulted in a higher fertility rate, but this action results in affected young rats, so their administration seems to be counter-productive.