Genetics and the nephron.

There have been phenomenal advances in our understanding of renal biology over the last 20 years through our ability to define the genetic mutations causing kidney disease in children. This review will take you through a trip down the nephron and highlight how these conditions may present to the paediatrician and the molecular basis for their biological effects.

Transcatheter and endovascular stent graft management of coarctation-related pseudoaneurysms.

OBJECTIVE: Surgical correction of congenital aortic coarctation can lead to a number of important problems including late pseudoaneurysm formation. Redo surgery has a significant risk. Endovascular stent graft repair is increasingly used but there are limited data regarding this indication. We describe the experience of two UK congenital referral centres. DESIGN: Retrospective analysis of patients treated with endovascular aortic stent grafting for late pseudoaneurysms. SETTING: Two UK congenital heart centres, Bristol Heart Institute and Leeds General Infirmary. PATIENTS: 17 patients were treated 2006-2012. This represents all patients treated with this technique. MAIN OUTCOME MEASURES: Procedural and postprocedure success and complications. RESULTS: The average time from index repair to endovascular repair of pseudoaneurysm was 24.6 years. The majority (70.6%) had patch aortoplasty as the original surgical procedure and 41.2% were not under follow-up or discharged. Stent grafting procedural success rate was 100%. Median hospital stay postprocedure was 3 days. There was no procedural mortality or immediate complication. There were four minor early and three minor late complications. Imaging follow-up was available for an average of 31.6 months (range 6-65 months). All patients have demonstrated positive remodelling of the pseudoaneurysm with no incidence of continued expansion or stent graft failure up to 5 years following implant. CONCLUSIONS: Endovascular stent graft treatment of pseudoaneurysms show promising results in a population who have a high risk of surgical re-intervention. Complication rates appear to be low and recovery is quick. Longer-term data remain essential to scrutinise stent graft performance in this situation.

Leprosy epidemics during history increased protective allele frequency of PARK2/PACRG genes in the population of the Mljet Island, Croatia.

INTRODUCTION: Two regulatory polymorphisms (rs1040079 and rs9356058) shared by PARK2 and PACRG genes were identified as major risk variants for leprosy susceptibility. The aim of this study was to investigate if allele frequencies of these polymorphisms in the isolated population of the island of Mljet, which served as a quarantine for leprosy patients during past centuries, were different to allele frequencies in two control populations with no history of leprosy. SUBJECTS AND METHODS: This study included 88 unrelated Caucasian individuals from the island of Mljet while two control groups included 93 individuals from the island of Rab and 160 individuals from the region of Split. Genotyping for rs1040079 and rs9356058 was performed by "real-time" PCR analysis. We also compared the allele frequency of the rs9356058 polymorphism from the population of Mljet with allele frequencies derived from the existing genome wide association scans in two additional island populations, Vis (924 subjects) and Korcula (909 subjects). RESULTS: We found a significant increase in the frequency of rs9356058 allele C in the population of Mljet when compared to both control groups. We also observed a significant increase in the frequency of rs1040079 allele A in the population of Mljet when compared with the population of Rab, however this increase was not significant when compared with the population of Split. Allele frequencies of both examined polymorphisms did not differ between the two control populations. Protective haplotype rs9356058-rs1040079 CA was also more frequent in the population of Mljet compared with the Rab and Split populations. In addition, an increase of frequency of rs9356058 allele C was also observed in the population of Mljet when compared with the frequency in the Korcula population. CONCLUSION: The results of our study show the association of polymorphisms rs9356058 and rs1040079 in gene PARK2/PACRG with leprosy. The results of our study indicate that exposure to leprosy and mortality in the population caused by leprosy on Mljet resulted in the selection of rs9356058 "protective" C allele in the PARK2 gene, while this was not observed in the two control groups. This is the first study to assess the genetic susceptibility to leprosy in a European population.

Blood tests and histological correlates in children with eosinophilic oesophagitis.

AIM: To determine the relationship between blood tests and oesophageal histology in Eosinophilic oesophagitis (EoE). METHODS: All children diagnosed with EoE at one hospital from 2000 to 2009 were considered for inclusion in this study. Three blood test results were analysed, blood eosinophil count, serum total immunoglobulin E (IgE) and radioallergosorbent tests (RAST) to common food allergens. Oesophageal histology was prospectively re-reviewed, and mean eosinophil counts were enumerated. Blood test results were correlated with oesophageal eosinophil counts using Spearman's rank test. RESULTS: Forty children (70% boys) were included in this study, median age at diagnosis 6.5 years (range 0-15). At the time of diagnosis, 78% of children had a raised blood eosinophil count, 90% had a raised serum total IgE and 83% had one or more positive RAST tests. The mean oesophageal eosinophil count was significantly correlated with both blood eosinophil count (p=0.008) and serum total IgE level (p=0.008). CONCLUSION: This study shows that blood tests are often abnormal in children with EoE at the time of diagnosis. Our data demonstrate an association between histological abnormalities and blood test results in children with EoE.

Clinical predictors of admission in infants with acute bronchiolitis.

BACKGROUND: Bronchiolitis is a significant cause of acute morbidity in the first 12 months of life and some infants with bronchiolitis are admitted to hospital. No studies have yet devised a scoring system to predict admission for routine use in the emergency department. AIM: To identify clinical predictors of hospital admission in infants with acute bronchiolitis and to devise a simple clinical risk scoring system which could be used to aid decision making in the emergency department. METHODS: All infants presenting with acute bronchiolitis to a dedicated paediatric emergency department from April 2009 to March 2010 were included in the study. Clinical predictors of admission were determined through case note review and logistic regression analysis. The strongest predictors of admission were assimilated into a simple clinical risk scoring system using widely accepted statistical methods. RESULTS: 449 infants presented with acute bronchiolitis during the study period (298 (66%) male, mean age 23±14.5 weeks). 163 (36%) infants were admitted to hospital. The five best predictors of admission (age, respiratory rate, heart rate, oxygen saturations and duration of symptoms) were incorporated into the bronchiolitis risk of admission scoring system. The area under the receiver operator characteristic curve was 0.81 (95% CI 0.77 to 0.85) at the optimal cut-off, demonstrating good diagnostic accuracy. CONCLUSIONS: The authors have identified important clinical predictors of admission in acute bronchiolitis. This information has been used to develop a simple clinical risk scoring system to aid decision making in the emergency department.

UK incidence of achalasia: an 11-year national epidemiological study.

AIM: To determine the incidence and examine the epidemiology of achalasia before the age of 16 years in the UK from 1998 to 2008. METHODS: 25 regional paediatric surgery referral centres were asked to provide demographic and epidemiological data on cases of childhood achalasia from 1998 to 2008. Incidence rates were calculated from national population estimates. The data collection method was validated in one centre. RESULTS: 228 patients from 24 centres were diagnosed with achalasia before 16 years in the UK from 1998 to 2008. The mean incidence from 1998 to 2008 was 0.18/10(5) children/year. Where additional data was provided (69-81% of cases) 56% of children were male and the mean age of diagnosis was 10.9 years. Logistic regression analysis showed a rising incidence, with an OR of 1.12 (95% CI 1.06 to 1.16) for having achalasia in each successive year. The validation of this methodology showed that 95% of true cases and no false cases were identified. CONCLUSIONS: The mean incidence of childhood achalasia in the UK from 1998 to 2008 is at least 0.18/10(5) children/year; this has risen over the last 11 years and compared to the only other study published in 1988.

Development and validation of a disease-specific quality-of-life measure for children with achalasia.

BACKGROUND: Achalasia is an uncommon oesophageal motility disorder occasionally affecting children. Children with achalasia can experience significant morbidity, and quality-of- life (QoL) has never been studied in this population. AIM: The aim was to develop a disease-specific quality-of-life (DS-QoL) measure for children with achalasia. METHODS: Item response theory methods were used to develop the DS-QoL measure. The construct validity of this measure was assessed by comparing items and domains with the generic PedsQL questionnaire. Reliability was assessed using Cronbach's alpha coefficient for internal consistency. RESULTS: 17 children completed the final DS-QoL measure, which consisted of 20 items in three domains. The completion rate for items was 99%. "Floor and ceiling effects" ranged from 0-19%. Construct validity was good with significant correlation between 2 domains and 2 items on the PedsQL. Reliability was excellent, with Cronbach's alpha coefficient ranging from 0.78-0.93. CONCLUSIONS: This DS-QoL measure is appropriate for use in children with achalasia and has shown good results in this validation study. Further work in higher numbers is necessary to determine discriminant validity and test-retest reliability.

Reduced quality of life in children with gastro-oesophageal reflux disease.

AIM: To assess self-reported Quality of life (QoL) in children with Gastro-oesophageal reflux disease (GORD) aged 5-18 and compare this with both disease and healthy control children in a prospective consecutive sample. METHODS: All children attending a tertiary paediatric gastroenterology clinic from February 2009 to May 2009 with GORD, chronic constipation and inflammatory bowel disease (IBD) were asked to complete the validated PedsQL generic QoL assessment (self-report) at their clinic appointment. The PedsQL considers physical, emotional, social and school domains and is scored from 0 to 100. Healthy children were also recruited from the same site. Groups were compared using the independent samples Student's t-test. RESULTS: A total of 184 children completed the assessment [103 (56%) male, mean age 10.7 years +/- 3.3] including 40 children with GORD, 44 with chronic constipation, 59 with IBD and 41 healthy children. QoL was significantly lower in the GORD group compared with both children with IBD (74 vs. 82) and healthy children (74 vs. 84), and was comparable to that of children with chronic constipation (74 vs. 74). CONCLUSIONS: Self-reported QoL in children with GORD attending a tertiary paediatric gastroenterology clinic is significantly reduced compared with both healthy children and children with IBD.