Importance of Studying Older Siblings of Patients Identified by Newborn Screening: a Single-Center Experience in Mexico

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.

Elevada mortalidad y discapacidad en niños mexicanos con enfermedad de orina con olor a jarabe de arce (EOJA) / Increased mortality and disability in a cohort of Mexican children with maple syrup urine disease

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.

Empirical antimicrobial therapy in pediatric patients with neutropenia and fever. Risk factor 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 wtih empirical antimicrobiial 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 percent and 56.3 percent for Cb/ak and Cz/ak, respectively. Fifty-seven episodes (33.3 percent) were microbiologically documented, gram-positive isolated in 38 percent and gram-negative in 49 percent. Risk factors associated significantly with treatment failure were acute mywlocytic leukemia (AML) (RR 2.59, CI 95 percent 1.42-4.7, p=0.003); bacteriological identification (RR= 4.41, CI 95 percent 2.21 - 8.8, p<0.001), and the presence of two or more sites of infection (RR= 2.89, CI 95 percent 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