Clinical and Genetic Characterization and Biochemical Correlation at Presentation in 48 Patients Diagnosed with Urea Cycle Disorders at the Hospital Juan P Garrahan, Argentina

Abstract The clinical and biochemical findings in a cohort of 51 patients with urea cycle disorders followed at the Hospital Garrahan, Buenos Aires, Argentina were analyzed at the time of diagnosis (3 female patients were excluded). Of this cohort, 13/48 patients had early-onset (EO), 23/48 had late-onset (LO), and 12/48 had a different presentation because they had a family risk background (FRB) and had been diagnosed since they were born. The most frequent deficiency disorder was OTCD (65%). The initial ammonium value was evaluated, being higher in the EO group, with a statistically significant difference when compared with LO and FRB. 15/48 patients fell into a coma at the time of diagnosis, mean ammonia was 829.54 μmol / L, and 33/48 did not fell into a coma, the mean ammonium was of 159.3 μmol / L (p = 0.001). 15 patients died: 62% EO, 22% LO (p=0.0216), 17% FRB. A molecular study was performed on 35 patients. Patients with EO presentation suffer the most severe forms and still have high morbimortality. On the other hand, LO forms are forms of less severity that are finally diagnosed as a result of one or more acute episodes.

Hiperamonemia secundaria a infección urinaria en un paciente con malformación del tracto urinario en pediatría: a propósito de un caso / Hyperammonemia secondary to urinary tract infection in patients with pediatric urinary tract malformation: a case report

Ammonium is an important source of nitrogen for amino acid synthesis and is necessary for normal acid base balance. When ammonium concentrations are high it becomes a toxic compound. Hyperammonemia is a metabolic emergency. When underdiagnosed and not treated appropriately, it produces severe neurological sequelae and/or death. The clinical presentation of hyperammonemic encephalopathy varies, and includes from personality disorders, psychiatric disorders, confusion, irritability, lethargy, seizures to coma. Hyperammonemia occurs with an increase in ammonium production, as in intestinal hemorrhage, or with a decrease in the elimination of ammonium, such as in congenital metabolic errors, hepatic insufficiency or drug intoxication. As we can see, it may have multiple origins, but congenital errors of metabolism are always suspected as one of the causes. However, there are less frequent causes, such as urinary tract infection, especially in predisposing conditions. We describe the case of a 2-year-old boy with a history of horseshoe kidney and right ureterohydronephrosis, surgical correction of imperforate anus and rectal bladder fistula. This patient presented hyperammonemia with encephalopathy (Glasgow 7/15) while undergoing a urinary infection with Corynebacterium riegelii. Hyperammonemia is the result of the production in the dilated urinary tract of large amounts of ammonium due to bacterial urease and its subsequent reabsorption in the systemic circulation. The patient improved clinically (Glasgow 15/15) after parenteral antibiotic therapy and urinary tract clearance

El amonio es una fuente importante de nitrógeno para la síntesis de aminoácidos y necesario para el balance ácido base; si se encuentra elevado, se convierte en un compuesto tóxico. La hiperamoniemia es una urgencia metabólica; cuando no es diagnosticada y tratada de manera oportuna, produce graves secuelas de tipo neurológico o la muerte. La presentación clínica de la encefalopatía hiperamoniémica es variable, pudiéndose observar trastornos en la personalidad, trastornos psiquiátricos, confusión e irritabilidad, letargia, convulsión y coma. La hiperamoniemia se presenta por aumento en la producción de amonio, como en la hemorragia intestinal, o por disminución de la eliminación del mismo, como ocurre en los errores congénitos del metabolismo, en la insuficiencia hepática o en la intoxicación por fármacos. Puede tener múltiples orígenes, pero los errores congénitos del metabolismo son una de las causas que siempre se sospechan. Sin embargo, existen causas menos frecuentes, como la infección del tracto urinario (sobre todo en condiciones que predispongan a las mismas). Describimos aquí el caso de un niño de 2 años, con antecedentes de riñón en herradura y ureterohidronefrosis derecha, corrección quirúrgica de ano imperforado y fistula recto vesical. Este paciente presentó hiperamoniemia con encefalopatía (Glasgow 7/15) mientras cursaba una infección urinaria por Corynebacterium riegelii. La hiperamoniemia es el resultado de la producción en el tracto urinario dilatado de grandes cantidades de amonio, debido a la ureasa bacteriana y su posterior reabsorción en la circulación sistémica. El paciente mejoró clínicamente (Glasgow 15/15) después de la terapia antibiótica parenteral y desobstrucción de tracto urinario

Fenilcetonuria de diagnóstico tardío / Late-diagnosed phenylketonuria

Introducción: La fenilcetonuria es el error congénito del metabolismo más frecuente y es la primera enfermedad del metabolismo con un tratamiento exitoso que evita la discapacidad intelectual. Tanto en el mundo como en la Argentina la fenilcetonuria inauguró la lista de enfermedades del tamizaje neonatal. La prueba de pesquisa neonatal tiene una relación entre el costo y la eficacia altamente favorable cuando la prueba de pesquisa da un resultado correcto; en caso contrario, esta prueba dejaría de ser eficaz. La fenilcetonuria clásica está causada por la deficiencia de la enzima fenilalanina hidroxilasa, responsable de la conversión de fenilalanina a tirosina. Objetivo: El objetivo del presente trabajo fue identificar pacientes con fenilcetonuria que no han sido diagnosticados por medio de la pesquisa neonatal; también, describir la presentación clínica de la enfermedad y analizar las causas de la falta de diagnóstico y de las potenciales repercusiones para los programas de pesquisa en la Argentina. Antecedentes históricos y de normativas: Se describen brevemente los antecedentes históricos de la fenilcetonuria y de la prueba de tamizaje neonatal. A partir de 1986, por medio de la Ley 23413, se establece la obligatoriedad de realizar la pesquisa neonatal de fenilcetonuria en la República Argentina. Materiales y métodos: Analizamos los pacientes con diagnóstico de fenilcetonuria que se encuentran en seguimiento en el Hospital de Pediatría S.A.M.I.C. Prof. Dr. Juan P. Garrahan desde 2000 hasta 2015. Hallamos una serie de casos con diagnóstico de fenilcetonuria que no han sido diagnosticados por la prueba de pesquisa neonatal, y los comparamos. Estudiamos las políticas de Salud Pública que reglamentan las pruebas de pesquisa en la Argentina. Resultado y conclusiones: Se identificaron tres pacientes con fenilcetonuria clásica de diagnóstico tardío con discapacidad intelectual. Los tres casos son sujetos oriundos de Neuquén, Argentina, con la prueba de pesquisa informada como "negativa"; en los tres, la muestra fue tomada tempranamente. Para que los programas de pesquisa sean efectivos, en primer lugar deben existir políticas sanitarias unificadas para todas las provincias argentinas, con un sistema de coordinación, formación, educación, evaluación y estadística eficiente. Es fundamental conocer el impacto que causa no detectar a estos pacientes ya que esta revisión demuestra que, ante el fracaso de la prueba de pesquisa neonatal, es posible evitar el resultado de tres personas con discapacidad intelectual, dos de ellas totalmente dependientes de sus familias y del sistema sanitario.

Introduction: Phenylketonuria (PKU) is the most prevalent disorder caused by an inborn error in aminoacid metabolism and it is the first disease that has a successful treatment that prevents intellectual disabilities. It is the first disorder included in neonatal screening programmes in the world, as it also happens in our country. Furthermore, newborn screening is a highly favorable cost-effective test when the screening test is well done, otherwise the cost effectiveness would be unfavorable. Classical PKU is caused by phenylalanine hydroxylase that catalyses the conversion of the essential amino acid L-phenylalanine to L-tyrosine. Objective: To identify patients with PKU who have not been diagnosed by means of newborn screening tests. Description of the clinical presentation of the disease. Analysis of the causes and potential implications for newborn screening programs. Historical antecedents and regulations: The historical background of PKU and of the disease neonatal screening tests are briefly described Since 1986 the National Law #23413 establishes the obligation of performing the Neonatal Screening of phenylketonuria in Argentina. Materials and methods: We analized patients with PKU admitted and followed up in the Hospital de Pediatría S.A.M.I.C. Prof. Dr. Juan P. Garrahan from 2000 to 2015 We found a case series of patients with phenylketonuria that have not been diagnosed by means of the newborn screening test and we compared them. Analysis of Public Health Care policies and the laws that regulate the screening tests in Argentina. Results and conclusion: Three patients were identified and diagnosed with classic PKU of late diagnosis and presented mental disability. The three cases were from Neuquén province, Argentina. The neonatal screening tests had reported as "negative" and the three samples had been taken early. If the screening programs are to be effective what is needed, in the first place, it is to have uniform health care policies with national coverage with an efficient system of coordination, training, education, evaluation and statistics. It is essential to know the impact that implies not to identify these patients. In this review, we have noticed that the failure of the newborn screening tests resulted in three patients with intellectual disabilities, two of them totally dependent on their families and the health care system.