Evolución clínica de niños con niveles plasmáticos de fenilalanina entre 2.1 y 6.0 mg/dl en el período neonatal / Clinical evolution of children with phenylalanine plasma levels between 2.1 and 6.0 mg/dl during the neonatal period

Introducción: La Academia Americana de Pediatría (AAP) ha clasificado la Fenilquetonuria (PKU) e Hiperfenilalaninemia (HFA) según la tolerancia de la ingesta de fenilalanina (FA) en: PKU clásica: 20 mg FA/kg/día, PKU moderada: 21 y 25 mg FA/kg/día y PKU leve: 25 y 50 mg FA/kg/día, e HFA benigna con dieta normal, manteniendo un nivel plasmático de FA entre 2,0 y 10,0 mg/dl. Objetivo: Evaluar la evolución clínica de 67 niños con valores de FA plasmática entre 2.1 y 6.0 mg/dL en el período neonatal. Resultados: Del total, 29 niños tenía entre 0 y 2 años, 23 entre 2 y 4 años y 15 niños eran mayores de 4 años de edad. El estado nutricional de 45 niños era normal, 14 niños estaban con sobrepeso u obesidad, y 8 casos tenían riesgo nutricional. Se determinó que 4 niños tenían una ingesta menor de 20 mg FA/kg/día, dos niños entre 21 y 25 mg FA/kg/día, 15 casos entre los 26 a 50 mg FA/kg/día y 46 niños estaban con dieta normal. Conclusión: Los recién nacidos con niveles de FA entre 2.1 y 6.0 mg/dl durante el período neonatal, tienen una evolución clínica y nutricional diferente, que puede ir desde una PKU clásica a una HFA benigna, por lo cual se recomienda mantener un control frecuente de FA sanguínea y una vigilancia nutricional, con un mínimo de 2 años de seguimiento.

Introduction: The American Academy of Pediatric (AAP) has classified Phenylketonuria (PKU) and Hyperphenylalaninaemias (HPhe) according to tolerance of phenylalanine (Phe) intake in: Classic PKU (20 mg Phe/kg/day), moderate PKU (between 21 and 25 mg Phe/kg/day) and mild PKU (between 25 and 50 mg Phe/kg/day), and benign HPhe with normal diet, maintaining blood Phe levels between 2,0 and 10,0 mg/dL. Objective: To evaluate the clinical evolution of 67 children with blood Phe values between 2,1 and 6.0 mg/dl in the neonatal period. Results: Of the total, 29 children were aged between 0 and 2 years, 23 between 2 and 4 years and 15 children were older than 4 years of age. The nutritional state of 45 children was normal, 14 children were overweight or obese, and 8 were at nutritional risk. Four children had Phe intake below 20 mg/kg/day, two children between 21 and 25 mg/kg/day; 15 cases between 26 to 50 mg/kg/day and 46 children were on normal diet. Conclusion: Newborns with blood Phe levels between 2,1 and 6,0 mg/dl in the neonatal period, had a different clinical and nutritional evolution, which could go from the classic PKU to a benign HPhe. Thus, it is recommended to keep a frequent control of plasmatic Phe levels and nutritional monitoring for a minimum of 2 years of follow up.

The time has come: a new scene for PKU treatment

Phenylketonuria (PKU) is one of the few genetic diseases in which mental retardation can be prevented. Hence, diagnosis and treatment must be established early. PKU treatment consists of a phenylalanine-restricted diet supplemented with a phenylalanine-free mixture of amino acids. However, it is difficult to adhere to this diet. In the last decade, a better comprehension of the biochemistry, genetics and molecular basis of the disease, as well as the need for easier treatment, led to the development of several new therapeutic strategies for PKU. In the present study, we evaluated these new therapeutic options in terms of theoretical basis, methodologies, efficacy, and costs.

Efficacy and safety of nateglinide in the treatment of type II diabetes mellitus.

Nateglinide a new short-acting D-phenylalanine derivative represents a new chemical class of drugs for treating type 2 diabetes that is pharmacologically and therapeutically distinct from currently existing agents. Studies in normal patients and those with type 2 diabetes have shown that nateglinide reduces mealtime blood glucose excursions by physiologic regulation of insulin secretion. Nateglinide binds to and inhibits the K+(ATP) channel of the beta-cell, causing membrane depolarisation, with a subsequent influx of extracellular calcium that results in insulin secretion. A total of 105 patients in 5 centres with type II diabetes mellitus were taken according to the inclusion criteria and given drug treatment and were evaluated on their improvement in fasting and postprandial plasma glucose and glycosylated haemoglobin values for efficacy, besides physician's assessment of the overall safety and efficacy. Nateglinide in a dose of 60 mg before three main meals was given and increased to a maximum of 120 mg thrice daily over the first 3-4 weeks. Nateglinide had to be taken 10 minutes before meals. Duration of treatment was 12 weeks. The patients showed decrease in fasting plasma glucose from 2nd week onwards and reduction in glycosylated haemoglobin by 6th week onwards. Postprandial glucose reduction was also significant at the end of 12th week. The frequency of adverse effects was low and no serious adverse effects were encountered.

Tratamiento nutricional de un niño con fenilcetonuria de diagnóstico neonatal: estudio de caso / Nutritional treatment of phenylketonuria diagnosed during the neonatal period: study of case

La fenilcetonuria es una enfermedad metabólica, de tipo autosómica recesivo asociada con retardo mental. Se presenta el caso de un lactante de 9 meses de edad, diagnosticado en el período neonatal y atendido en el Centro de Atención Nutricional Infantil Antímano (CANIA), durante el año de 1999. El tratamiento nutricional consistió en dieta restringida en fenilalanina con aporte de tirosina utilizando una fórmula especial libre en fenilalanina y alimentos complementarios con bajo contenido en fenilalanina. Durante los nueve meses de seguimiento se realizaron 24 controles con un interválo promedio de 7 a 15 días, donde intervino un equipo multidisplinario. La intervención nutricional estuvo dirigida a mantener los niveles séricos de fenilalanina entre 2 y 6 mg/dL, lo cual requirió de ajuste continuos en las cantidades de leche materna, fórmula libre en fenilalanina y alimentos complementarios con bajo contenido fenilalanina, iniciados a partir de los 5 meses de edad, con un aporte promedio de 30 mg/Kg/día de fenilalanina. Estos ajustes se hicieron de acuerdos a las condiciones clínicas, necesidades nutricionales, ingesta calórica y a los niveles séricos de fenilalanina. Uno de los pilares fundamentales en el éxito del tratamiento es el aspecto educativo que permite que crear conciencia de la enfermedad y el entrenamiento de la madre

Life-long treatment for phenylketonuria.

Life-long low-phenylalanine diet is recommended as an additional determinant to achieve the maximal success in the treatment of phenylketonuria (PKU). In this context education of teenage patients with PKU is essential.

ATP diphosphohydrolase activity in synaptosomes from cerebral cortex of rats subjected to chemically induced phenylketonuria

ATP diphosphohydrolase (apyrase)(EC3.6.1.5) activity was measured in synaptosomes from cerebral cortex of Wistar rats of both sexes subjected to experimental phenylketonuria, i.e., chemical hyperphenylaninemia induced by subcutaneous administration of 5.2 µmol phenylalanine/g body weight (twice a day) plus 0.9 µmol p-chlorophenylalanine/g body weight (once a day). ATP diphosphohydrolase specific activity (nmol Pi min-1 mg protein-1) of synaptosomes was significantly decreased compared to controls for both ATp (from 147.6 to 129.9) and ADP (from 70.2 to 63.1) hydrolysis one hour after single administration of the drugs to 35-day old rats. Chronic treatment was performed from the 6th to the 28th postpartum day. The enzyme specific activity of synaptosomes was measured one week after the last administration of the drugs and was significantly reduced compared to controls for both ATP (from 164.1 to 150.2) and ADP (from 76.3 to 62.1) hydrolysis. The in vitro effects of the drugs on the synaptosome enzyme specific activity were also investigated. Phenylalnine alone or associated with p-chlorophenylalanine significantly reduced enzyme specific activity for both ATP (from 150.2 to 136.0) and ADP (from 70.5 to 59.3) nucleotides as substrates. Since ATP diphosphohrolase seems to play an important role in neurotransmission, these findings may be related to the neurological dysfunction characteristic of human phenylketonuria