First experience of enzyme replacement therapy with idursulfase in Spanish patients with Hunter syndrome under 5 years of age: case observations from the Hunter Outcome Survey (HOS).

Hunter syndrome (mucopolysaccharidosis type II [MPS II], OMIM309900) is a rare X-linked lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulphatase, resulting in accumulation of glycosaminoglycans (GAGs), multisystem organ failure and early death. Enzyme replacement therapy (ERT) with idursulfase is commercially available since 2007. Early access programs were established since 2005. However, limited information on the effects of ERT in young children is available to date. The aim of this analysis was therefore to determine the effects of ERT on patients younger than 5 years of age. We report data from six Spanish patients with confirmed Hunter syndrome who were younger than 5 years at the start of ERT, and had been treated with weekly intravenous infusions of idursulfase between 6 and 14 months. Baseline and treatment data were obtained from the Hunter Outcome Survey (HOS). HOS is an international database of MPS II patients on ERT or candidates to be treated, that collects data in a registry manner. HOS is supported by Shire Human Genetic Therapies, Inc. (Cambridge, MA, USA). At baseline, all patients showed neurological abnormalities, including ventriculomegaly, hydrocephaly, cerebral atrophy, perivascular changes and white matter lesions. Other signs and symptoms included thoracic deformity, otitis media, joint stiffness and hepatosplenomegaly, demonstrating that children under 5 years old can also be severely affected. ERT reduced urinary GAG levels, and reduced spleen (n = 2) and liver size (n = 1) after only 8 months. Height growth was maintained within the normal range during ERT. Joint mobility either stabilized or improved during ERT. In conclusion, this case series confirms the early onset of signs and symptoms of Hunter syndrome and provides the first evidence of ERT beneficial effects in patients less than 5 years of age. Similar efficacy and safety profiles to those seen in older children can be suggested, although further studies including a direct comparison with older patients would still be required.

Consideraciones sobre la Ley 41/2002. Peculiaridades en pediatría / Considerations concerning Law 41/2002: particularities in pediatrics

Varias son las normas y leyes que tratan de establecer un reglamento básico que regule la relación entre el médico y el paciente y los derechos y deberes que ambos tienen durante dicho proceso. Por ello, muchos son los organismos que han realizado declaraciones o normas jurídicas relativas a este tema (UNESCO, OMS, Unión Europea, etc.). Todos estos preceptos se hallan resumidos en la Ley 41/2002, promulgada por las Cortes españolas. De la misma forma, dentro de nuestro país, varias comunidades autónomas han regulado mediante una ley estos aspectos, haciendo especial hincapié en la información clínica y el consentimiento informado (Cataluña, Galicia, Navarra, Castilla y León, etc.).Mención especial requiere la relación médico-paciente en los casos pediátricos, ya que ésta es diferente y, además, generalmente suelen intervenir en ella más individuos (padres o tutores en la mayoría de los casos). La Ley 41/2002 establece ciertas características especiales en la relación médico-paciente pediátrico y marca los límites legales en la relación entre el sanitario, el niño y sus familiares o tutores. Pero el debate actualmente va más allá, ya que entra en juego el concepto de «menor maduro», según el cual el límite para establecer la mayoría de edad en cuanto a decisiones sobre su propia persona queda más difuminado. De esta forma, se regula la posibilidad de que las decisiones sobre la salud del niño pueda tomarlas él mismo, o al menos sugerir lo que él considera mejor para sí mismo, en el momento en que el profesional sanitario lo considere «maduro» (AU)

There are several standards and laws that attempt to establish basic regulations to control the relationship between the doctor and the patient and the rights and obligations of each during the process. Therefore, many organizations (such as the United Nations Educational, Scientific and Cultural Organization [UNESCO], the World Health Organization [WHO], the European Union. etc) have issued statements or legal standards regarding this issue. All these precepts have been summarized in law 41/2002, promulgated by the Spanish Parliament. Likewise, a number of autonomous regions in our country (Catalonia, Galicia, Navarre, Castile-León, etc.) now regulate these aspects by law, with special emphasis on clinical information and informed consent. The doctor-patient relationship in pediatric cases is different, and other individuals are involved in it (mainly parents or legal tutors).Law 41/2002 establishes special characteristics for this doctor pediatric patient relationship and specifies the legal limits relative to the relationship among the health worker, the child and his or her family or tutors. However the debate nowadays goes beyond this. The new concept of the “mature minor” comes into play. In this concept, the limit for establishing the age of majority regarding decisions concerning his or her own self becomes blurrier. Thus, the decisions to be made over the health of the child are standardized: when the physician considers the patient “mature” enough, the child himself will be allowed to make decisions, or atleast suggest what he considers better for himself/herself (AU)

Aportación de la resonancia magnética en el diagnóstico de la aciduria glutárica de tipo I / The contribution of magnetic resonance imaging to the diagnosis of type I glutaric aciduria

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[Diagnostic test in emergency departments for bacterial infections in infants younger than 12 months]. / Orientación diagnóstica en la unidad de urgencias en lactantes menores de 12 meses con infección bacteriana.

OBJECTIVE: To evaluate clinical and analytic numeric data that may help the emergency departments to identify bacterial infections in infants. PATIENTS AND METHODS: A retrospective study of 430 infants with bacterial growth in cultures (culture from blood, 30; urine, 207; stools, 193, and/or cerebrospinal fluid, n 25) was performed. These patients were compared with a control group (n 430), randomly selected from patients aged less than 12 months with negative cultures who were hospitalized with suspected infection. Neonates and surgical patients were excluded from both groups. Statistical analysis was performed using Student's t-test for independent samples, Levene's test for the study of equality of variances, bivariate correlation and one-factor ANOVA, and receiver-operating characteristic (ROC) curves and odds ratios were calculated when statistically significant (p < 0.05) results were obtained. These analyses were performed using the SPSS 10.0 statistical software package. RESULTS: Of the infants admitted to the pediatric unit, 11.7 % had at least one positive bacterial culture. Temperature (p 0.005), leucocyte count (p 0.003), percentage of neutrophils (p < 0.0001) and C-reactive protein (p < 0.0001) were significantly higher in infants with positive cultures. In invasive infections significant differences were found in sex (more frequent in males) (p 0.03), heart rate (p < 0.0001) and respiratory rate (p 0.003). In the ROC curves, the best diagnostic yield was obtained for C-reactive protein (0.93 for a cutoff value of 29 mg/l, 86 % specificity and 91 % sensitivity). CONCLUSION: C-reactive protein is essential for diagnosis of bacterial infection in infants in the emergency department.

Orientación diagnóstica en la unidad de urgencias en lactantes menores de 12 meses con infección bacteriana / Diagnostic test in emergency departments for bacterial infections in infants younger than 12 months

Objetivo: Analizar los datos clinicoanalíticos relacionados con el diagnóstico de infección bacteriana en la unidad de urgencias en niños con edad inferior a un año. Pacientes y métodos Estudio retrospectivo de 430 niños menores de un año con cultivos centrales positivos (hemocultivos, 30; cultivos de líquido cefalorraquídeo (LCR), 25; urocultivos, 207; coprocultivos, 193). Estos pacientes se compararon con un grupo control (n 430), seleccionados de forma aleatoria del resto de pacientes que ingresaron con edad inferior a 12 meses, sospecha de infección y cultivos centrales negativos. Se excluyeron los pacientes de la unidad de neonatología y los niños ingresados para cirugía. Se realizaron el test de la t de Student para muestras independientes, prueba de Levene para estudio de igualdad de varianzas, correlaciones bivariadas y ANOVA de un factor, así como curvas ROC (receiver-operating characteristic) y odds ratio cuando se obtuvieron resultados con significación estadística (p < 0,05). Dichos estudios se obtuvieron con el paquete estadístico SPSS 10,0. Resultados El 11,7 per cent de los niños ingresados con edad inferior a un año tenían algún cultivo central positivo. De las variables analizadas tuvieron significación estadística la temperatura (p 0,005), el recuento leucocitario (p 0,003), el porcentaje de segmentados (p < 0,0001) y proteína C reactiva (PCR) (p < 0,0001). En las infecciones invasivas existió además significación estadística para el sexo (predominio de varones) (p 0,03), frecuencia cardíaca (p < 0,0001) y frecuencia respiratoria (p 0,003). En las curvas ROC el mejor rendimiento diagnóstico se obtuvo con la PCR (con un corte óptimo de 29 mg/l se obtuvo un área bajo la curva de 0,93 con especificidad de 86 per cent y sensibilidad de 91 per cent). Conclusión La PCR es fundamental para el diagnóstico de infección bacteriana en la sala de urgencias en niños menores de un año (AU)