RESUMEN

Microvillus inclusion disease (MVID) is associated with specific variants in the MYO5B gene causing disrupt epithelial cell polarity. MVID may present at birth with intestinal symptoms or with extraintestinal symptoms later in childhood. We present 3 patients, of whom 2 are siblings, with MYO5B variants and different clinical manifestations, ranging from isolated intestinal disease to intestinal disease combined with cholestatic liver disease, predominant cholestatic liver disease clinically similar to low-gamma-glutamyl transferase PFIC, seizures, and fractures. We identified 1 previously unreported MYO5B variant and 2 known pathogenic variants and discuss genotype-phenotype correlations of these variants. We conclude that MVID may present phenotypically different and mimic other severe diseases. We suggest that genetic testing is included early during diagnostic investigations of children with gastrointestinal and cholestatic presentation.

RESUMEN

OBJECTIVES: Paediatric acute liver failure (P-ALF) is a rare condition and is associated with a high mortality rate. Management of P-ALF aims to stabilise vital organ functions and to remove circulating toxins and provide vital plasma factors that are lacking. High-volume plasmapheresis (HVP) removes protein-bound substances and improves survival in adult ALF. It is unknown if this effect can be extrapolated to P-ALF. The aim of this study is to report the safety and feasibility of HVP in P-ALF. METHODS: Children with P-ALF were offered HVP if bilirubin was higher than 200 µmol/L or if the aetiology was toxic hepatitis. HVP was performed with fresh frozen plasma corresponding to 10% of the body weight on a minimum of 3 consecutive days. Diagnostics, biochemical and clinical data during HVP as well as outcome data after 3 months were collected from 2012 to 2019 and retrospectively analysed. RESULTS: Sixteen children were treated by HVP and completed at least one series of three treatment sessions with HVP. The only complication seen was an increase in pH > 7.55 in three children within the first 12 hours and was corrected with hydrochloric acid. No bleeding or septic episodes were noted during HVP. Eight children survived without liver transplantation, two survived after successful grafting and a total of six children died. The liver injury unit score between survivors with their own liver and the rest, the two groups was significantly different (P = 0.005). CONCLUSION: HVP with fresh frozen plasma is feasible and well tolerated in children with P-ALF. No serious adverse events and no procedure-related mortality were observed.

Asunto(s)

Enfermedad Hepática Inducida por Sustancias y Drogas , Fallo Hepático Agudo , Trasplante de Hígado , Adulto , Niño , Humanos , Fallo Hepático Agudo/etiología , Fallo Hepático Agudo/terapia , Plasmaféresis , Estudios Retrospectivos

RESUMEN

BACKGROUND: We performed a 12-month cohort study of the stability and resilience of the intestinal microbiota of healthy children in daycare in Denmark in relation to diarrheal events and exposure to known risk factors for gastrointestinal health such as travelling and antibiotic use. In addition, we analyzed how gut microbiota recover from such exposures. RESULTS: We monitored 32 children in daycare aged 1-6 years. Fecal samples were submitted every second month during a one-year observational period. Information regarding exposures and diarrheal episodes was obtained through questionnaires. Bacterial communities were identified using 16S rRNA gene sequencing. The core microbiota (mean abundance > 95%) dominated the intestinal microbiota, and none of the tested exposures (diarrheal events, travel, antibiotic use) were associated with decreases in the relative abundance of the core microbiota. Samples exhibited lower intra-individual variation than inter-individual variation. Half of all the variation between samples was explained by which child a sample originated from. Age explained 7.6-9.6% of the variation, while traveling, diarrheal events, and antibiotic use explained minor parts of the beta diversity. We found an age-dependent increase of alpha diversity in children aged 1-3 years, and while diarrheal events caused a decrease in alpha diversity, a recovery time of 40-45 days was observed. Among children having had a diarrheal event, we observed a 10x higher relative abundance of Prevotella. After travelling, a higher abundance of two Bacteroides species and 40% less Lachnospiraceae were seen. Antibiotic use did not correlate with changes in the abundance of any bacteria. CONCLUSION: We present data showing that Danish children in daycare have stable intestinal microbiota, resilient to the exposures investigated. An early age-dependent increase in the diversity was demonstrated. Diarrheal episodes decreased alpha diversity with an estimated recovery time of 40-45 days.

Asunto(s)

Bacterias/aislamiento & purificación , Guarderías Infantiles/estadística & datos numéricos , Microbioma Gastrointestinal , Intestinos/microbiología , Factores de Edad , Bacterias/clasificación , Bacterias/genética , Niño , Preescolar , Estudios de Cohortes , Dinamarca , Diarrea/microbiología , Heces/microbiología , Femenino , Humanos , Lactante , Masculino , Filogenia

RESUMEN

Background: Kidney disease has been reported in adults with inflammatory bowel disease (IBD) and is regarded an extraintestinal manifestation or more rarely a side effect of the medical treatment. Methods: In this cross-sectional study we describe the extent of kidney pathology in a cohort of 56 children with IBD. Blood and urine samples were analyzed for markers of kidney disease and ultrasonography was performed to evaluate pole-to-pole kidney length. Results: We found that 25% of the patients had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease. The median kidney size compared with normal children was significantly reduced. In a multivariate linear mixed model, small kidneys significantly correlated with the use of infliximab, whereas the use of enteral nutritional therapy was associated with larger kidneys. Conclusion: Children with IBD are at risk of chronic kidney disease, and the risk seems to be increased with the severity of the disease.

Asunto(s)

Enfermedades Inflamatorias del Intestino/complicaciones , Riñón/patología , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Adolescente , Índice de Masa Corporal , Niño , Preescolar , Estudios de Cohortes , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab , Complejo de Antígeno L1 de Leucocito/orina , Modelos Lineales , Lipocalina 2/orina , Masculino , Análisis Multivariante , Prednisolona , Insuficiencia Renal Crónica/etiología , Ultrasonografía

RESUMEN

Dientamoeba fragilis is an intestinal protozoan of debated clinical significance. Here, we present cross-sectional and longitudinal observations on D. fragilis in children aged 0 to 6 years from a 1-year multi-day-care-center cohort study set in Copenhagen, Denmark. The inclusion period for the cohort was 2009 through 2012. Stool samples collected from the children were accompanied by questionnaires completed by the parents or guardians of the children. Using real-time PCR, D. fragilis was detected in the first stool sample from 97 of 142 (68.3%) children. We evaluated the associations between seven plausible risk factors (age, sex, having siblings, having domestic animals at home, having had infant colic, recent history of intake of antibiotics, and recent history of travel abroad) as well as six reported symptoms (lack of appetite, nausea, vomiting, abdominal pain, weight loss, and diarrhea) and testing positive for D. fragilis The final multivariable model identified being >3 years old and having a history of recent travel abroad as risk factors for testing positive for D. fragilis Moreover, univariable analyses indicated that having siblings was a risk factor. There was no statistical association between a recent history of gastrointestinal symptoms and testing positive for D. fragilis Among the 108 children who were represented by ≥2 samples and thus included in the longitudinal analysis, 32 tested negative on the first sample and positive later, and the last sample from each of the 108 children was positive. The results are in support of D. fragilis being a common enteric commensal in this population.

Asunto(s)

Guarderías Infantiles , Dientamoeba/aislamiento & purificación , Dientamebiasis/epidemiología , Niño , Preescolar , Estudios Transversales , Dinamarca/epidemiología , Heces/parasitología , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Encuestas y Cuestionarios

RESUMEN

We describe two children with oedematous malnutrition; one admitted to a nutrition unit in Uganda and another to a paediatric department in Denmark. Both children received nutritional therapy and recovered. Although oedematous malnutrition is rarely seen in industrialized countries, the condition has been associated with chronic diseases. It is a life-threatening condition, and the pathogenesis remains unknown. Specialized nutrition products have been developed for low-resource clinics in developing countries, however, no specific protocols or products are available for physicians in Denmark.

Asunto(s)

Edema , Desnutrición , Preescolar , Dinamarca , Edema/patología , Edema/terapia , Humanos , Lactante , Masculino , Desnutrición/patología , Desnutrición/terapia , Terapia Nutricional , Uganda

RESUMEN

Enteroaggregative Escherichia coli (EAEC) has been associated with persistent diarrhea, reduced growth acceleration, and failure to thrive in children living in developing countries and with childhood diarrhea in general in industrialized countries. The clinical implications of an EAEC carrier-status in children in industrialized countries warrants clarification. To investigate the pathological significance of an EAEC carrier-state in the industrialized countries, we designed a 1-year dynamic cohort study and performed follow-up every second month, where the study participants submitted a stool sample and answered a questionnaire regarding gastrointestinal symptoms and exposures. Exposures included foreign travel, consumption of antibiotics, and contact with a diseased animal. In the capital area of Denmark, a total of 179 children aged 0-6 years were followed in a cohort study, in the period between 2009 and 2013. This is the first investigation of the incidence and pathological significance of EAEC in Danish children attending daycare facilities. Conventional microbiological detection of enteric pathogens was performed at Statens Serum Institute, Copenhagen, Denmark, and at Hvidovre Hospital, Copenhagen, Denmark. Parents completed questionnaires regarding gastrointestinal symptoms. The EAEC strains were further characterized by serotyping, phylogenetic analysis, and susceptibility testing. EAEC was detected in 25 (14%) of the children during the observational period of 1 year. One or more gastrointestinal symptoms were reported from 56% of the EAEC-positive children. Diarrhea was reported in six (24%) of the EAEC positive children, but no cases of weight loss, and general failure to thrive were observed. The EAEC strains detected comprised a large number of different serotypes, confirming the genetic heterogeneity of this pathotype. EAEC was highly prevalent (n = 25, 14%) in Danish children in daycare centers and was accompanied by gastrointestinal symptoms in 56% of the infected children. No serotype or phylogenetic group was specifically linked to children with disease.

Asunto(s)

Guarderías Infantiles/estadística & datos numéricos , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Escherichia coli/aislamiento & purificación , Animales , Antibacterianos , Niño , Preescolar , Estudios de Cohortes , Coinfección/microbiología , ADN Bacteriano/genética , Dinamarca/epidemiología , Diarrea/epidemiología , Diarrea/microbiología , Escherichia coli/genética , Infecciones por Escherichia coli/transmisión , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/microbiología , Humanos , Lactante , Recién Nacido , Prevalencia , Factores de Riesgo

RESUMEN

AIM: Diarrhoea is very common in children attending day care centres. The aim of this study was to examine certain predisposing risk factors for an association with diarrhoea, including foreign travel, treatment with antibiotics, having household pets, infant colic, bottle feeding, using a pacifier and low birthweight. METHODS: A dynamic one-year follow-up cohort study comprising 179 children from 36 day care centres was conducted from September 2009 to July 2013 in Copenhagen, Denmark. Questionnaires were sent to the children's parents or legal guardians every two months for a year, requesting information on gastrointestinal symptoms and exposure. A logistic regression was performed to identify the odds ratios of different risk factors for diarrhoea. RESULTS: The odds ratios for diarrhoea were 1.97 (0.93-4.20) for children with a history of infant colic, 1.91 (0.90-4.04) for low birthweight children and 1.45 (0.74-2.82) for children who had used antibiotics. Having a pet in the household had a possible protective effect towards diarrhoeal events, with an odds ratio of 0.47 (0.20-1.09). CONCLUSION: A history of infant colic, low birthweight, and to a lesser extent antibiotic use, possibly increased the risk of diarrhoea in Danish children in day care centres.

Asunto(s)

Antibacterianos/efectos adversos , Guarderías Infantiles , Cólico/complicaciones , Diarrea/etiología , Recién Nacido de Bajo Peso , Preescolar , Dinamarca , Diarrea Infantil/etiología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Oportunidad Relativa , Factores de Riesgo , Encuestas y Cuestionarios

RESUMEN

OBJECTIVES: Infection during the induction phase of childhood acute lymphoblastic leukemia (ALL) is a major cause of morbidity and mortality. Several studies have indicated that genetically determined low serum levels of mannose-binding lectin (MBL), a component of innate immunity, are associated with increased risk for infections in patients receiving chemotherapy. Thus, these patients have been proposed to be candidates for MBL replacement therapy. METHODS: In a population-based cohort of 137 children with ALL treated at a single pediatric hematology-oncology center with an almost identical chemotherapy regimen, we studied the relationship between polymorphisms in the MBL gene (MBL2) and the MBL2 promoter and the risk of infections during the first 50 d of induction therapy. RESULTS: No increased frequency of infection was seen for the children with genotypes encoding serum low levels of MBL. A higher incidence of fever (P < 0.004), infectious events (P = 0.025), days with neutropenia (P < 0.001) and a higher frequency of antimicrobial therapy (P = 0.0007) were seen in the young age group (<2.5 yr) compared with the older age group (> or =2.5 yr), independent of the MBL genotype. CONCLUSIONS: MBL deficiency did not influence the frequency of infections in children receiving induction chemotherapy for ALL, not even in the youngest children (<2.5 yr) whom we found to have the highest risk for infections.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Infecciones/epidemiología , Lectina de Unión a Manosa/deficiencia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Factores de Edad , Alopurinol/administración & dosificación , Antiinfecciosos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bacteriemia/epidemiología , Bacteriemia/etiología , Candidiasis/epidemiología , Candidiasis/etiología , Niño , Preescolar , Estudios de Cohortes , Susceptibilidad a Enfermedades , Doxorrubicina/administración & dosificación , Femenino , Fiebre/epidemiología , Fungemia/epidemiología , Fungemia/etiología , Genotipo , Humanos , Inmunidad Innata , Huésped Inmunocomprometido , Incidencia , Lactante , Infecciones/tratamiento farmacológico , Infecciones/etiología , Masculino , Lectina de Unión a Manosa/genética , Neutropenia/inducido químicamente , Neutropenia/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Prednisolona/administración & dosificación , Regiones Promotoras Genéticas , Inducción de Remisión , Vincristina/administración & dosificación

RESUMEN

The purpose of the current study was to test the hypothesis that an altered fat distribution in elderly healthy subjects and in patients with type-2 diabetes contributes to high circulating levels of interleukin (IL)-6 and tumor necrotic factor (TNF)-alpha, which secondly is related to lower muscle mass. Twenty young controls, (20-35 yr), 20 healthy elderly subjects (65-80 yr) and 16 elderly patients with type 2 diabetes (65-80 yr) were included in a cross sectional study. Plasma levels of TNF-alpha and IL-6 were measured after an overnight fast. Dual-energy X-ray absorptiometry and total body potassium counting measured truncal fat, appendicular skeletal muscle mass (ASM) and body cell mass (BCM), respectively. TNF-alpha, IL-6 and the relative truncal fat mass were higher in elderly compared with young controls. ASM was lower in diabetic men than in young controls and BCM was lower in elderly men compared with young men. TNF-alpha and IL-6 were correlated with the absolute as well as the relative truncal fat mass in univariate regression analyses. Similar results were found in multivariate linear regression analyses after adjusting for the effect of age and gender. TNF-alpha was related to lower ASM and BCM in elderly men both in a univariate regression analysis and a multivariate regression analysis. In conclusion, high plasma levels of TNF-alpha and IL-6 in elderly healthy people and in patients with type 2 diabetes are associated with increased truncal fat mass, suggesting that cytokines are partly derived from this adipose tissue bed. Furthermore, TNF-alpha was related to lower ASM and BCM, suggesting that TNF-alpha contributes to sarcopenia in ageing.

Asunto(s)

Tejido Adiposo/patología , Envejecimiento/inmunología , Diabetes Mellitus Tipo 2/inmunología , Interleucina-6/sangre , Músculo Esquelético/patología , Factor de Necrosis Tumoral alfa/metabolismo , Tejido Adiposo/inmunología , Adulto , Anciano , Envejecimiento/patología , Composición Corporal , Femenino , Humanos , Masculino , Músculo Esquelético/inmunología , Atrofia Muscular/inmunología , Atrofia Muscular/patología

RESUMEN

Epidemiological data indicate that acute lymphoblastic leukemia (ALL) could be induced by interactions between the immune system and early childhood infections. Mannose-binding lectin (MBL) plays a critical role in the immune response in early childhood before specific immune protection develops. We investigated whether there may be an association between childhood ALL and low-producing MBL genotypes. Serum MBL levels depend on normal (A) or defective (O) alleles, and on normal (Y) or reduced (X) promoter activities. For this study, 137 noninfants with ALL and 250 controls were classified into 3 MBL genotype groups according to their influence on the serum level of functional MBL: group I, YA/YA and YA/XA (higher levels); group II, XA/XA and YA/O (intermediate levels); and group III, MBL insufficiency with XA/O or O/O (MBL-deficient) genotypes. Compared with controls, cases more often had low-level genotypes (I/II/III: 63 [46%]/44 [32%]/30 [22%] vs 145 [58%]/65 [26%]/40 [16%]; P =.02) and MBL deficiency (8.8% vs 2.8%; P =.009). Thus, the ALL odds ratio for MBL-deficient versus nondeficient individuals was 3.3 (95% CI, 1.3-8.7), whereas the ALL odds ratio for group I versus group II/III genotypes was 0.62 (95% CI, 0.41-0.94). MBL group III patients were significantly younger at diagnosis than patients in group I/II (median, 3.9 vs 5.2 years; P =.04). The study shows that the presence of low-level MBL genotypes is associated with an increased risk of childhood ALL, particularly with early age at onset.

Asunto(s)

Lectinas de Unión a Manosa/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Alelos , Estudios de Casos y Controles , Niño , Preescolar , Frecuencia de los Genes , Variación Genética , Genotipo , Humanos , Incidencia , Lactante , Lectinas de Unión a Manosa/sangre , Lectinas de Unión a Manosa/deficiencia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología