Caracterización de errores innatos del metabolismo intermediario en pacientes mexicanos / Characterization of inborn errors of intermediary metabolism in mexican patients

Introducción: Los errores innatos del metabolismo intermediario (EIMi) son enfermedades genéticas heterogéneas que causan importante morbimortalidad y representan un reto diagnóstico. El objetivo de este trabajo es describir el número, el tipo y las características clínicas de los pacientes con EIMi en un hospital pediátrico de alta especialidad. Material y métodos: Estudio retrospectivo de 204 expedientes de pacientes diagnosticados con EIMi por sospecha clínica, de enero del 2000 a diciembre del 2012, analizados antes y después de la implementación de la espectrometría de masas en tándem (MS/MS) como herramienta de tamiz selectivo. Resultados: En los 204 casos analizados, se encontraron 25 diferentes tipos de EIMi: 102 con acidurias orgánicas y 100 con aminoacidopatías y 2 con defectos de la beta oxidación. La introducción de la MS/MS incrementó el número de casos detectados en 50%. Los pacientes fueron enviados por 13 diferentes servicios médicos, siendo los pediatras los que remitieron más casos. El intervalo promedio entre el inicio de los síntomas y el diagnóstico fue de 18 meses. Conclusión: En los niños enfermos mexicanos estudiados se encontró una gran variedad de EIMi, destacando los defectos del propionato y la enfermedad de orina de jarabe de arce. En esta población analizada, el diagnóstico de la enfermedad metabólica se realizó en forma muy tardía. Estos resultados pueden servir como evidencia para incorporar los EIMi al tamiz neonatal ampliado, o en su defecto para que se realice el diagnóstico selectivo en todos los niños hospitalizados con datos clínicos indicativos (AU)

Introduction: Inborn errors of intermediary metabolism (IEiM) are a group of heterogeneous genetic diseases that are diagnostically challenging and cause significant morbidity and mortality. The aim of this study is to perform a descriptive analysis of the number, type, and clinical features, in a series of cases with IEiM identified through selective diagnosis in a highly specialized pediatric hospital. Materials and methods: A retrospective study was performed from January of 2000 to December of 2012 by analyzing the files of 204 patients with an IEiM, by selective screening, before and after the implementation of tandem mass spectrometry (MS/MS).Results: A total of 25 different types of IEiM were found in the 204 files; 102 organic acidurias, 100 aminoacidopathies, and 2 fatty acid oxidation disorders. The introduction of MS/MS increased the number of cases detected by 50%. Patients were referred from 13 different specialists, with pediatricians being the most active. The average interval between onset of symptoms and diagnosis was 18 months. Conclusion: Among the sick Mexican children studied, a wide variety of IEiM was found, propionate defects and maple syrup urine disease being noteworthy. The diagnosis of metabolic disease was delayed in the population studied. These results present evidence to perhaps incorporate IEiM into an expanded newborn screening, or else to perform selective diagnosis in all hospitalized children with suggestive clinical data (AU)

[Characterization of inborn errors of intermediary metabolism in mexican patients]. / Caracterización de errores innatos del metabolismo intermediario en pacientes mexicanos.

INTRODUCTION: Inborn errors of intermediary metabolism (IEiM) are a group of heterogeneous genetic diseases that are diagnostically challenging and cause significant morbidity and mortality. The aim of this study is to perform a descriptive analysis of the number, type, and clinical features, in a series of cases with IEiM identified through selective diagnosis in a highly specialized pediatric hospital. MATERIALS AND METHODS: A retrospective study was performed from January of 2000 to December of 2012 by analyzing the files of 204 patients with an IEiM, by selective screening, before and after the implementation of tandem mass spectrometry (MS/MS). RESULTS: A total of 25 different types of IEiM were found in the 204 files; 102 organic acidurias, 100 aminoacidopathies, and 2 fatty acid oxidation disorders. The introduction of MS/MS increased the number of cases detected by 50%. Patients were referred from 13 different specialists, with pediatricians being the most active. The average interval between onset of symptoms and diagnosis was 18 months. CONCLUSION: Among the sick Mexican children studied, a wide variety of IEiM was found, propionate defects and maple syrup urine disease being noteworthy. The diagnosis of metabolic disease was delayed in the population studied. These results present evidence to perhaps incorporate IEiM into an expanded newborn screening, or else to perform selective diagnosis in all hospitalized children with suggestive clinical data.

Causes of delay in referral of patients with phenylketonuria to a specialized reference centre in Mexico.

OBJECTIVE: To expose causes leading to the delayed arrival of phenylketonuria (PKU) patients at a governmental reference centre (RC), and to describe their clinical characteristics. Material and methods PKU files registered during the past 18 years at the National Institute of Pediatrics in Mexico City were evaluated. Patients were classified into two groups according to their age at arrival: Group I (early reference), patients arriving during the first month of life; and Group II (late reference), those who arrived after thirty days of age. Time and causes of delay were documented. RESULTS: Of 57 recorded files, 10 were classified in Group I and 47 in Group II. Causes leading to the late arrival of Group II patients were absence of routine newborn screening (NBS), PKU not included in the routine NBS, sampling after the recommended age, false negative result, results without interpretation and/or instructions to follow, delayed notification of results, poor medical criteria of attending physician, difficulties in obtaining confirmatory tests, and administrative failures. CONCLUSION: The main cause of late referral of PKU patients was the absence of PKU testing. As a developing country, Mexico still faces challenges in the proper functioning and expansion of the NBS programme. Most PKU patients arrived at the RC late, presenting with varying degrees of the clinical spectrum. Incorporating PKU testing into the already established Mexican NBS system and adding quality indicators to guarantee proper operation in all NBS phases is necessary to achieve the goal of identifying, referring, diagnosing, and treating patients promptly.

Variabilidad interinstitucional del tamiz neonatal en México / Institutional variability of neonatal screening in Mexico

Introducción. Actualmente, los avances tecnológicos han hecho factible el tamiz neonatal (TN) para un número cada vez mayor de enfermedades. En México, la normatividad vigente se ha mantenido sin cambios desde 1988, contemplando únicamente la detección del hipotiroidismo congénito; sin embargo, el TN ha evolucionado de manera diferenciada en el sector salud. Objetivo: conocer la variabilidad del número de enfermedades detectadas mediante el TN y las metodologías utilizadas para su realización en las distintas instituciones del sistema de salud mexicano. Métodos. Se realizaron entrevistas telefónicas con los coordinadores estatales del Programa de TN. Resultados. Algunas instituciones realizan el tamiz para una enfermedad, mientras que otras lo practican hasta para 60 enfermedades. Las metodologías empleadas van de 1 a 5. Conclusión. Existe gran variabilidad en el número de enfermedades que se tamizan, así como en las metodologías empleadas; dicha variabilidad depende del lugar del nacimiento y la adscripción laboral de los padres. La variabilidad conduce a inequidad en la oportunidad de que a los recién nacidos se les detecten enfermedades congénitas graves, que tienen un alto potencial generador de discapacidad, por lo que es importante que se establezcan políticas de salud equitativas, justas y modernas sobre el TN en México.

Introduction. Recently, the development of technology has reached the availability of neonatal screening (NS) for an increasing number of diseases. In Mexico, the actual official regulation makes obligatory the detection of only one disease -hypothyroidism. Despite this, the regulation has remained without changes since 1988. Panels involved in NS have evolved differently in the Mexican health sector. We undertook this study to determine the variability of the NS panels and the number of detected diseases as well as the diverse methodologies used for their determination in the different institutions of the Mexican health system. Methods. Telephone interviews were made to the directors of the NS program for each federal entity and institution. Results. We found that some institutions only screen for one disease, whereas others screen for up to 60 diseases. Methodology variation was 1 to 5. Conclusions. There is great variability in the number of diseases detected in newborns as well as in the methodologies used. Such inconsistency depends on the place of birth and the parents' employment for insurance affiliation. This difference leads to unequal opportunities for the detection of severe inherited diseases with high potential of impaired development. It is important to establish equal, fair and modern health policies in regard to NS in Mexico.

Empirical antimicrobial therapy in pediatric patients with neutropenia and fever. Risk factors for treatment failure.

BACKGROUND: The use of combinations of antibiotics has been the cornerstone of therapy for febrile patients with cancer and severe neutropenia. Each empirical regimen should be selected according to the epidemiology and susceptibility patterns in each center. We describe here the experience with empirical antimicrobial treatments in pediatric patients with cancer, fever and severe neutropenia, and identify the risk factors associated with treatment failure. METHODS: This is a prospective study including 145 patients with cancer, and 171 episodes of neutropenia and fever. Blood cultures were taken before initiating empirical treatment: a) carbenicillin (400 mg/kg/day) plus amikacin (21 mg/kg/day) (Cb/ak), and b) ceftazidime (100 mg/kg/day), plus amikacin at the same dosage (Cz/ak). RESULTS: The overall response rate was 54.9% and 56.3% for Cb/ak and Cz/ak, respectively. Fifty-seven episodes (33.3%) were microbiologically documented, gram-positive isolated in 38% and gram-negative in 49%. Risk factors associated significantly with treatment failure were acute myelocytic leukemia (AML) (RR 2.59, CI 95% 1.42-4.7, p = 0.003); bacteriological identification (RR = 4.41, CI 95% 2.21-8.8, p < 0.001), and the presence of two or more sites of infection (RR = 2.89, CI 95% 1.03-8.11, p = 0.03). CONCLUSIONS: The rates of response are similar to the combinations used in the hospital (Cb/ak, Cz/ak). The risk factors associated with treatment failure were AML diagnosis, bacteriological identification, and the presence of two or more sites of infection.