ABSTRACT
Abstract Introduction: Any abnormal newborn screening (NBS) test should be subjected to appropriate diagnostic tests and should be followed. Once the newborn has been diagnosed and treated, the family should receive comprehensive genetic services. Aim: To present the experience of studying older siblings of patients with inborn errors of metabolism (IEM) identified by NBS in a single-national follow-up reference center. Methods: A retrospective analysis of medical files of the IEM patients detected by NBS was conducted. All those older siblings who tested positive for the same IEM of the patient detected by newborn screening were included. Results: A total of 26 positive siblings from 18 families with seven different IEM were found (phenylketonuria, argininemia, glucose-6-phosphate dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase deficiency, dihydropteridine reductase deficiency, tyrosinemia type 3, and medium chain acyl-CoA dehydrogenase deficiency). The age range of the affected siblings was 2 to 19 years old, with a mean age of 8.5 years. Ten older siblings (38.5%) had clinical consequences for the disease, including severe intellectual disability. Conclusions: It is necessary to study older siblings, and family history and genetic counseling of all NBS-detected families should be recommended, especially in countries where expanded NBS programs are beginning.
ABSTRACT
Abstract: Objective: Inborn errors of metabolism (IEM) are genetic conditions that are sometimes associated with intellectual developmental disorders (IDD). The aim of this study is to contribute to the metabolic characterization of IDD of unknown etiology in Mexico. Materials and methods: Metabolic screening using tandem mass spectrometry and fluorometry will be performed to rule out IEM. In addition, target metabolomic analysis will be done to characterize the metabolomic profile of patients with IDD. Conclusion: Identification of new metabolomic profiles associated with IDD of unknown etiology and comorbidities will contribute to the development of novel diagnostic and therapeutic schemes for the prevention and treatment of IDD in Mexico.
Resumen: Objetivo: Los errores innatos del metabolismo (EIM) son condiciones genéticas que pueden asociarse con trastornos del desarrollo intelectual (TDI). El objetivo de este estudio es contribuir a la caracterización metabólica de los pacientes con TDI de etiología desconocida. Material y métodos: Se realizará un tamiz metabólico mediante espectrometría de masas-tándem y fluorometría para descartar EIM; además, se analizará el perfil metabolómico de los pacientes con TDI. Conclusión: La identificación de perfiles metabolómicos asociados con los TDI de etiología desconocida contribuirá al desarrollo de nuevos esquemas diagnósticos y terapéuticos para la prevención y tratamiento de los TDI en México.
Subject(s)
Humans , Male , Female , Child , Adolescent , Young Adult , Metabolomics/methods , Intellectual Disability/etiology , Intellectual Disability/epidemiology , Metabolism, Inborn Errors/diagnosis , Mass Screening , Health Surveys , Tandem Mass Spectrometry , Fragile X Syndrome/diagnosis , Fragile X Syndrome/epidemiology , Mexico/epidemiologyABSTRACT
Introducción: La enfermedad de jarabe de arce es una enfermedad genética que produce crisis de cetoacidosis y deterioro neurológico progresivo que llevan a un coma fatal. El inicio del tratamiento temprano es determinante en el pronóstico. Objetivo: Describir las características de una cohorte de pacientes mexicanos con enfermedad de orina con olor a jarabe de arce (EOJA). Material y métodos: Se hizo un análisis retrospectivo de casos de EOJA de 1991 a 2006. Resultados: Encontramos 36 pacientes (16 niñas y 20 niños). Tres fueron inicialmente detectados mediante tamiz neonatal, uno de ellos realizado en México y los otros dos en el extranjero. Estos últimos recibieron tratamiento oportuno y exhiben desarrollo psicomotor normal. El caso detectado en México no recibió tratamiento adecuado y falleció. Los otros 33 pacientes se diagnosticaron entre los 2 y los 73 meses de edad mediante tamiz metabólico (postsintomático) ante la sospecha clínica. Todos los pacientes sintomáticos presentaron resultado positivo a la prueba de dinitrofenilhidrazina y aminoácidos ramificados elevados. La hipotonía, rechazo al alimento, y las crisis convulsivas fueron los síntomas más frecuentes. En esta cohorte, la mortalidad fue del 50 % (18/36) y el 81.2 % de los sobrevivientes (13/18) muestran actualmente retraso psicomotor. Discusión: Es necesario establecer en México un modelo de atención integral para la EOJA que incluya la detección presintomática preventiva, el tratamiento temprano, el seguimiento y asesoramiento genético.
INTRODUCTION: Maple syrup urine disease (MSUD) is a genetic disorder that produces ketoacidosis crises and neurological complications often leading to death. The age of diagnosis and treatment determine a child's adequate and healthy outcome. OBJECTIVE: Describe the characteristics of a pediatric Mexican cohort with MSUD. MATERIAL AND METHODS: Retrospective analysis of MSUD cases seen at our Metabolic Unit between 1991- 2006. RESULTS: We studied 36 patients; three were initially detected through neonatal screening, one of them done in Mexico and two in the United States. The latter were given timely treatment and developed normally, both intellectually and physically. The patient detected in Mexico was not given adequate treatment and died at 3 months of age. The remaining 33 patients were diagnosed between 2-24 months using standard biochemical tests performed after symptoms became noticeable. All symptomatic patients had high levels of branched-chain amino acids. Hypotonia, refusal to eat and seizures were the most frequent symptoms. The cohort's mortality was 50% (18/36), while 81.2% (13/18) of survivors displayed cognitive impairment. DISCUSSION: Mexico needs a comprehensive treatment protocol for the care of MSUD patients including newborn screening, early treatment, follow-up and genetic counseling.