RESUMEN

BACKGROUND: Acute cerebellitis (AC) in children and adolescents is an inflammatory disease of the cerebellum due to viral or bacterial infections but also autoimmune-mediated processes. OBJECTIVE: To investigate the frequency of autoantibodies in serum and CSF as well as the neuroradiological features in children with AC. MATERIAL AND METHODS: Children presenting with symptoms suggestive of AC defined as acute/subacute onset of cerebellar symptoms and MRI evidence of cerebellar inflammation or additional CSF pleocytosis, positive oligoclonal bands (OCBs), and/or presence of autoantibodies in case of negative cerebellar MRI. Children fulfilling the above-mentioned criteria and a complete data set including clinical presentation, CSF studies, testing for neuronal/cerebellar and MOG antibodies as well as MRI scans performed at disease onset were eligible for this retrospective multicenter study. RESULTS: 36 patients fulfilled the inclusion criteria for AC (f:m = 14:22, median age 5.5 years). Ataxia was the most common cerebellar symptom present in 30/36 (83 %) in addition to dysmetria (15/36) or dysarthria (13/36). A substantial number of children (21/36) also had signs of encephalitis such as somnolence or seizures. In 10/36 (28 %) children the following autoantibodies (abs) were found: MOG-abs (n = 5) in serum, GFAPα-abs (n = 1) in CSF, GlyR-abs (n = 1) in CSF, mGluR1-abs (n = 1) in CSF and serum. In two further children, antibodies were detected only in serum (GlyR-abs, n = 1; GFAPα-abs, n = 1). MRI signal alterations in cerebellum were found in 30/36 children (83 %). Additional supra- and/or infratentorial lesions were present in 12/36 children, including all five children with MOG-abs. Outcome after a median follow-up of 3 months (range: 1 a 75) was favorable with an mRS ≤2 in 24/36 (67 %) after therapy. Antibody (ab)-positive children were significantly more likely to have a better outcome than ab-negative children (p = .022). CONCLUSION: In nearly 30 % of children in our study with AC, a range of abs was found, underscoring that autoantibody testing in serum and CSF should be included in the work-up of a child with suspected AC. The detection of MOG-abs in AC does expand the MOGAD spectrum.

Asunto(s)

Autoanticuerpos , Encefalitis , Adolescente , Niño , Preescolar , Humanos , Ataxia , Cerebelo/diagnóstico por imagen , Encefalitis/diagnóstico por imagen , Inflamación , Estudios Retrospectivos

RESUMEN

BACKGROUND: Only sparse data exist about children with septic shock in Europe. The present study aimed to evaluate demographics, treatment, outcome and risk factors for mortality in Western Germany. PATIENTS: Children with septic shock aged 2 months to 17 years. METHODS: In a multi-center retrospective study of 20 children's hospitals data were obtained and analyzed by chart review. Risk factors for mortality were identified and assessed by multivariate regression analysis. RESULTS: Overall mortality in 83 cases with septic shock was 25% (21 patients). Significant risk factors were high PRISM III score, low pH, low arterial systolic blood pressure, presence of disseminated intravascular coagulation and extent of multi-organ failure, but not lactate (p=0.05) and base excess (p=0.065). Mortality in hospitals which treated 10 or more patients (category 1) was 17% and increased to 22% in hospitals which treated 3-6 patients (category 2). In hospitals with only 1 or 2 patients (category 3) mortality rate was 61% (p<0.01 when compared to category 1 or 2). A stepwise increase was also seen in the severely sick patients according to PRISM III (>19): category 1: 23%, category 2: 40%, category 3: 62.5% (p<0.05 for comparison of category 1 and 3). Multivariate analysis of significant risk factors revealed low number of treated patients as the only individual risk factor for mortality. CONCLUSION: Mortality from pediatric septic shock in an urban area in Western Germany is high. Disease severity and treatment in a department with few cases were associated with increased mortality.

Asunto(s)

Infecciones Bacterianas/epidemiología , Choque Séptico/epidemiología , Población Urbana/estadística & datos numéricos , Virosis/epidemiología , Adolescente , Infecciones Bacterianas/mortalidad , Infecciones Bacterianas/terapia , Niño , Preescolar , Terapia Combinada , Estudios Transversales , Femenino , Alemania , Mortalidad Hospitalaria , Hospitales Pediátricos/estadística & datos numéricos , Hospitales Universitarios/estadística & datos numéricos , Humanos , Lactante , Puntaje de Gravedad del Traumatismo , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Masculino , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/mortalidad , Infecciones Oportunistas/terapia , Estudios Prospectivos , Factores de Riesgo , Choque Séptico/mortalidad , Choque Séptico/terapia , Resultado del Tratamiento , Virosis/mortalidad , Virosis/terapia

RESUMEN

Adenoviruses (AdV) are opportunistic pathogens that can lead to severe infections and respiratory failure (acute respiratory distress syndrome, ARDS) with high mortality in immunosuppressed patients. Cidofovir (CDV) has been used in adenoviral disease in bone marrow transplant recipients. Two pediatric liver transplant recipients with disseminated adenoviral disease and ARDS were treated with reduction of immunosuppression, CDV, and inhaled nitric oxide (iNO). CDV 1 mg/kg was given three times per week intravenously with intravenous hydration and oral probenecid. Viral suppression and clinical improvement was achieved. AdV hepatitis did not occur, and graft function was preserved, although acute rejection occurred in both patients. Adverse effects were mild and transient not requiring dose modification. Severe hypoxemia was reversed with iNO 10-20 p.p.m. CDV treatment of AdV infections in organ transplant recipients and other immunocompromised patients should be further investigated in prospective studies.

Asunto(s)

Infecciones por Adenovirus Humanos/tratamiento farmacológico , Antivirales/administración & dosificación , Citosina/análogos & derivados , Depuradores de Radicales Libres/administración & dosificación , Trasplante de Hígado , Óxido Nítrico/administración & dosificación , Organofosfonatos/administración & dosificación , Insuficiencia Respiratoria/tratamiento farmacológico , Infecciones por Adenovirus Humanos/etiología , Administración por Inhalación , Atresia Biliar/cirugía , Cidofovir , Citosina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Terapia de Inmunosupresión/efectos adversos , Lactante , Fallo Hepático Agudo/cirugía , Complicaciones Posoperatorias , Insuficiencia Respiratoria/etiología

RESUMEN

This paper describes the second patient found to be affected with a deficiency of transaldolase (TALDO1; EC 2.2.1.2). Clinically, this patient presented in the neonatal period with several signs of severe liver failure: severe coagulopathy, low serum protein, elevated blood ammonia, and hypoglycaemia. She had generalized oedema, moderate muscular hypotonia, and dysmorphic signs. Liver size was decreased, and the spleen was moderately enlarged. There was severe cardiomegaly. The clinical course was characterized by intractable liver failure and progressive myocardial hypertrophy. The child died at the age of 18 days from respiratory failure. In urine, elevations of erythritol, arabitol and ribitol were found, suggesting a deficiency of transaldolase. Enzyme studies in cultured fibroblasts showed undetectable transaldolase activity. DNA sequence analysis of the TALDO1 gene showed a homozygous missense mutation (575G>A), resulting in an amino acid alteration at position 192 (arginine to histidine, R192H). This amino acid is part of the catalytic site of the transaldolase protein. Discovery of this second patient affected with transaldolase deficiency and liver failure suggests that this disorder has a heterogeneous clinical presentation with highly variable severity.

Asunto(s)

Cardiomiopatías/etiología , Fallo Hepático Agudo/etiología , Errores Innatos del Metabolismo/complicaciones , Índice de Severidad de la Enfermedad , Transaldolasa/genética , Cardiomiopatías/diagnóstico , Cardiomiopatías/metabolismo , Resultado Fatal , Femenino , Humanos , Recién Nacido , Enfermedades del Recién Nacido/diagnóstico , Enfermedades del Recién Nacido/etiología , Enfermedades del Recién Nacido/genética , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/metabolismo , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/genética , Monosacáridos/orina , Mutación Missense , Polímeros/metabolismo , Transaldolasa/deficiencia

RESUMEN

Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. Due to virtual absence of acid alpha-glucosidase, patients with classical infantile Pompe disease develop progressive cardiomyopathy, skeletal muscle weakness and respiratory insufficiency leading to death in early infancy. We report on the results of a phase II clinical trial including two patients with classical infantile Pompe disease receiving enzyme replacement therapy over a period of 48 weeks by weekly infusions. Recombinant acid alpha-glucosidase was derived from the milk of transgenic rabbits. Safety was evaluated by recording adverse events while clinical efficacy was evaluated by ventilator-free survival, left ventricular mass index, motor development as well as histologic and biochemical analysis of muscle biopsies. This therapy was in general well-tolerated. There was an overall improvement in left ventricular mass, cardiac function, skeletal muscle function and histological appearance of skeletal muscle.

Asunto(s)

Enfermedad del Almacenamiento de Glucógeno Tipo II/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , alfa-Glucosidasas/uso terapéutico , Esquema de Medicación , Evaluación de Medicamentos , Electrocardiografía/métodos , Femenino , Glucógeno/metabolismo , Humanos , Lactante , Masculino , Actividad Motora/efectos de los fármacos , Músculos/metabolismo , Músculos/patología , Miocardio/metabolismo , Miocardio/patología , Proteínas Recombinantes/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , alfa-Glucosidasas/efectos adversos , alfa-Glucosidasas/metabolismo

RESUMEN

UNLABELLED: Congenital alveolar proteinosis and misalignment of lung vessels are rare disorders. We report on five infants of consanguineous kindred. All infants were delivered at term after uneventful pregnancies. Shortly after birth they developed respiratory failure and severe persistent pulmonary hypertension. All died despite intensive care. Lung tissue of two infants was studied. Histological examination revealed combination of alveolar proteinosis and misalignment of lung vessels in one patient, alveolar proteinosis in the other. Immunostaining demonstrated surfactant protein B (SP-B) deficiency in both patients' lungs. In a further sibling, analysis of broncho-alveolar lavage fluid showed decreased surfactant protein. PCR and direct sequence analysis of the SP-B gene revealed three novel mutations. One of them, a single base deletion, shifts the reading frame at amino acid 122 and creates a premature termination of translation in exon 6. No mature SP-B protein is produced. CONCLUSION: Surfactant protein B deficiency caused by mutations of the respective gene and misalignment of lung vessels can concur. Both diseases may have a pathogenetic factor in common.

Asunto(s)

Pulmón/irrigación sanguínea , Mutación , Proteolípidos/genética , Alveolos Pulmonares , Surfactantes Pulmonares/genética , Vasos Sanguíneos/anomalías , Consanguinidad , Resultado Fatal , Femenino , Humanos , Recién Nacido , Pulmón/anomalías , Pulmón/patología , Masculino , Linaje , Reacción en Cadena de la Polimerasa , Proteolípidos/metabolismo , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/patología , Surfactantes Pulmonares/metabolismo

RESUMEN

Hypophosphatasia is a rare inherited disorder characterized by defective bone mineralization and deficiency of serum and tissue liver/ bone/kidney tissue alkaline phosphatase (L/B/K ALP) activity. We report the characterization of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 9 families affected by severe hypophosphatasia. Fourteen distinct mutations were found, 3 of which were previously reported in the North American or Japanese populations. Seven of the 11 new mutations were missense mutations (M45L, R119H, G145V, C184Y and H154Y, D289V, E459K), the four others were 2 single nucleotide deletions (544delG and 1172delC), a mutation affecting donor splice site (862 + 5A) and a nonsense mutation (R411X).

Asunto(s)

Fosfatasa Alcalina/deficiencia , Fosfatasa Alcalina/genética , Hipofosfatasia/enzimología , Hipofosfatasia/genética , Mutación/genética , Sustitución de Aminoácidos/genética , Humanos , Mutación Missense/genética

RESUMEN

We performed a prospective study to see whether axillary temperature accurately reflects rectal temperature in premature and sick mature newborns nursed in incubators and whether axillary temperature measurement is better tolerated than rectal measurement. 561 pairs of rectal and axillary temperatures were obtained in 20 infants. Mean axillary temperatures were 0.16 degree C (SD 0.33 degree C) lower than rectal temperatures. In infants < 1000 g axillary temperatures were only 0.06 degree C (SD 0.30 degree C) lower than rectal temperatures whereas in infants > 2500 g axillary temperatures were 0.37 degree C (SD 0.38 degree C) lower than rectal temperatures. Our results show that axillary and rectal temperatures are interchangeable in extremely premature infants. In newborn infants however 0.4 degree C should be added to axillary temperatures to make them comparable to rectal temperatures. Assessment of infant behaviour during temperature measurement by the nursing staff showed that infants tolerated rectal better than axillary temperature measurements. The decision which kind of measurement will be performed can be taken individually for every infant.

Asunto(s)

Temperatura Corporal/fisiología , Recien Nacido Prematuro/fisiología , Termómetros , Axila , Femenino , Humanos , Conducta del Lactante , Recién Nacido , Masculino , Recto , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por Computador/instrumentación

RESUMEN

Mutations and polymorphisms within the human SP-B locus have been linked to fatal congenital alveolar proteinosis (CAP) and associated with respiratory distress syndrome (RDS), respectively. In the present study we used PCR and direct sequence analysis of the SP-B gene of three individuals from a family with CAP to search for additional SP-B mutations resulting in CAP and/or polymorphisms that could be used as markers in association studies of RDS and/or CAP. We found three novel mutations/polymorphisms in this family. One is a C/A substitution at nt 1013 at the splice junction of intron 2-exon 3. A second one is a single base T deletion at nt 1553 in exon 4. The single base (T) deletion at nucleotide 1553 (1553delT) shifts the reading frame at amino acid 122(122delT) and creates a premature termination codon at amino acid 214 in exon 6. The mutated gene produces no mature SP-B protein. Genotype analysis from the nuclear family carrying this mutation showed that both parents and three of the four living children are heterozygous for the mutation. One of the four living children is homozygous for the normal allele and a child that died in the perinatal period from CAP is homozygous for the mutation. A third change is a C/T substitution at nt 1580 in exon 4 that changes amino acid 131 from threonine to isoleucine (Thr131Ile). The location of a previously reported mutation, 121ins2 (1), is only 4 nt upstream of 122delT, and the missense mutation Thr131Ile (exon 4) is only 27 nt downstream of 122delT. These changes are within or in close proximity to a CCTG sequence and a poly(C) tract, both of which are shown in other systems to be mutation hotspots. The 122delT occurs within the CCTG and the poly(C) tract sequences, the Thr131Ile occurs 26 nt downstream from the CCTG sequence, and the 121ins2 occurs 2 nt upstream from CCTG sequence and within the poly(C) tract. The present observations suggest that the short SP-B sequence containing the CCTG motif and the poly(C) tract is a mutation hotspot.

Asunto(s)

Exones/genética , Mutación del Sistema de Lectura , Proteolípidos/genética , Proteinosis Alveolar Pulmonar/genética , Surfactantes Pulmonares/genética , Secuencia de Bases , Codón de Terminación , Femenino , Heterocigoto , Homocigoto , Humanos , Recién Nacido , Masculino , Datos de Secuencia Molecular , Linaje , Fenotipo , Mutación Puntual , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Proteinosis Alveolar Pulmonar/congénito , Proteinosis Alveolar Pulmonar/mortalidad , Análisis de Secuencia de ADN , Eliminación de Secuencia

RESUMEN

Acute cerebellar swelling is an emergency because of brainstem compression as well as upward or downward cerebellar herniation. Few childhood cases are on record, with fatal outcome in three out of six. We report a girl with probable Epstein-Barr virus-associated cerebellar swelling who recovered completely with steroid treatment after a stormy course. Review of the literature showed that all three patients, including our own, who recovered fully, received high-dose steroids in contrast to none of the four patients who died or survived with sequelae. Neuroimaging and evoked potential studies are useful for early diagnosis and disease monitoring. We conclude that for the time being high-dose steroid treatment is advocated in patients with acute infectious or parainfectious cerebellar swelling.

Asunto(s)

Corticoesteroides/uso terapéutico , Edema Encefálico , Enfermedades Cerebelosas/patología , Enfermedades Cerebelosas/virología , Herpesvirus Humano 4/patogenicidad , Enfermedad Aguda , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/etiología , Edema Encefálico/patología , Niño , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Femenino , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inmunoglobulina M/inmunología , Imagen por Resonancia Magnética , Resultado del Tratamiento

RESUMEN

Nitric oxide (NO) is produced by various cell types in the human respiratory tract. Endogenously produced nitric oxide is detectable in the exhaled air of healthy individuals. Exhaled NO has been shown to be increased in airway inflammation, most probably due to cytokine-mediated activation of NO synthases. To assess whether NO can serve as a marker of inflammation in cystic fibrosis (CF) lung disease, we measured exhaled NO in CF patients with a chemiluminescence analyser. Single breath measurements were performed in 27 stable CF patients (age range, 6-40 years) and 30 non-smoking controls (age range, 6-37 years). Exhaled NO concentrations were 9.1 +/- 3.6 ppb in the controls and 5.9 +/- 2.6 ppb (P < 0.001) in CF patients. To account for room air NO concentrations on the measurement of exhaled NO, we also calculated the difference between exhaled NO and ambient NO concentrations. Difference values were also significantly lower in CF compared with controls (P < 0.0001). In CF patients there was a positive correlation between exhaled NO and forced vital capacity (r = 0.43, P = 0.033), suggesting that exhaled NO is lower in patients with severe lung disease than in those with mild disease. We conclude that measurements of exhaled NO in CF does not reflect activity of CF airway inflammation. The decreased concentrations of exhaled NO may be due to inhibitory effects of inflammatory cytokines on NO syntheses in the airways and alveolar epithelial cells or to increased retention in airway secretions.

Asunto(s)

Fibrosis Quística/metabolismo , Enfermedades Pulmonares/diagnóstico , Óxido Nítrico/biosíntesis , Adolescente , Adulto , Biomarcadores/análisis , Pruebas Respiratorias , Estudios de Casos y Controles , Niño , Fibrosis Quística/complicaciones , Femenino , Humanos , Mediciones Luminiscentes , Enfermedades Pulmonares/etiología , Masculino , Óxido Nítrico/análisis

Asunto(s)

Enfermedades del Prematuro/tratamiento farmacológico , Óxido Nítrico/uso terapéutico , Acidosis/complicaciones , Acidosis/tratamiento farmacológico , Enfermedades en Gemelos , Hipoxia Fetal/complicaciones , Hipoxia Fetal/tratamiento farmacológico , Humanos , Hipercapnia/complicaciones , Hipercapnia/tratamiento farmacológico , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/fisiopatología , Pulmón/anomalías , Masculino

RESUMEN

Calcium carbonate is widely used as an oral phosphorus binder to control hyperphosphatemia in children on maintenance hemodialysis. Intestinal calcium absorption may induce hypercalcemia, particularly if calcitriol is given simultaneously. In adults, calcium acetate binds phosphorus more effectively than calcium carbonate, while reducing the frequency of hypercalcemic events. We therefore compared calcium acetate with calcium carbonate in nine pediatric patients on long-term maintenance hemodialysis. Following a 1-week withdrawal of phosphorus binders, calcium carbonate was administered for 7 weeks; after a second withdrawal, calcium acetate was given for another 7 weeks. All patients received calcitriol regularly. Both agents lowered the serum phosphorus concentration significantly (calcium carbonate 5.7 +/- 1.4 vs. 7.7 +/- 2.1 mg/ dl, P < 0.005; calcium acetate 5.8 +/- 1.4 vs. 7.8 +/- 2.0 mg/dl, P < 0.005). Significantly less elementary calcium was ingested with calcium acetate than with calcium carbonate: 750 (375-1,500) vs. 1,200 (0-3,000) mg calcium/day, P < 0.0001. Wit calcium carbonate serum calcium increased significantly. The number of episodes of hyperphosphatemia or hypercalcemia did not differ between treatments. Intact plasma parathyroid hormone (PTH) decreased significantly with both phosphate binders, and serum 25-hydroxyvitamin D3 increased. There was a close relationship between serum phosphorus and PTH in prepubertal but not in pubertal patients. We conclude that hyperphosphatemia can be controlled effectively by both calcium acetate and calcium carbonate in pediatric hemodialysis patients. The oral load of elementary calcium is reduced significantly by binding phosphorus with calcium acetate instead of calcium carbonate; nevertheless, hypercalcemic episodes remain equally frequent with both phosphate binders.

Asunto(s)

Ácido Acético/metabolismo , Carbonato de Calcio/metabolismo , Fosfatos/metabolismo , Diálisis Renal , Adolescente , Adulto , Calcitriol/sangre , Niño , Femenino , Humanos , Masculino , Hormona Paratiroidea/sangre