Heterozygous missense variant in EIF6 gene: A novel form of Shwachman-Diamond syndrome?

Shwachman-Diamond syndrome (SDS) is a rare multisystem ribosomal biogenesis disorder characterized by exocrine pancreatic insufficiency, hematologic abnormalities and bony abnormalities. About 90% of patients have biallelic mutations in SBDS gene. Three additional genes-EFL1, DNAJC21 and SRP54 have been reported in association with a SDS phenotype. However, the cause remains unknown for ~10% of patients. Herein, we report a 6-year-old Chinese boy, who presented in the neonatal period with pancytopenia, liver transaminitis with hepatosplenomegaly and developmental delay, and subsequently developed pancreatic insufficiency complicated by malabsorption and poor growth. Exome sequencing identified a novel de novo heterozygous variant in EIF6 (c.182G>T, p.Arg61Leu). EIF6 protein inhibits ribosomal maturation and is removed in the late steps of ribosomal maturation by SBDS and EFL1 protein. Given the interaction of EIF6 with SBDS and EFL1, we postulate heterozygous variants in EIF6 as a novel cause of Shwachman-Diamond-like phenotype. We compared the phenotype of our patient with those in patients with mutation in SBDS, EFL1, DNAJC21, and SRP54 genes to support this association. Identification of more cases of this novel phenotype would strengthen the association with the genetic etiology.

Seventeen years of Kasai portoenterostomy for biliary atresia in a single Southeast Asian paediatric centre.

AIM: Biliary atresia (BA) has preponderance in Asian populations with Kasai portoenterostomy (KP) regarded as the first-line standard of care. Yet reports from Southeast Asia remain scant. This study reviews the demographics, short- and medium-term outcomes for our cohort, and evaluates prognostic factors for outcome. METHODS: All patients diagnosed with BA between January 1997 and December 2013 were included. Clinical data were obtained from medical records. Jaundice clearance was defined as total bilirubin < 20 µmol/L within 6 months after KP. Two-year and 5-year native liver survival (NLS) were determined. Prognostic factors examined included gender, ethnicity, associated anomalies, age at KP, post-KP cholangitis and clearance of jaundice within 6 months. RESULTS: Of 58 patients studied, 31(53.4%) were male. Median age at time of KP was 53 days (range: 28-127). Ethnic distribution showed 32 (55.2%) Chinese, 16 (27.6%) Malays and 10 (17.2%) others. Twenty-one (36.2%) patients achieved jaundice clearance by 6 months. Two-year NLS rate was 36 out of 50 (72%), while 5-year NLS rate was 16 out of 35 (45.7%). Only clearance of jaundice within 6 months had a significant association with NLS (P = 0.006). All other factors showed no significant impact on outcome. CONCLUSIONS: Our short- and medium-term outcomes after KP for BA are comparable with those reported by most international centres. However, prognostic factors such as age at KP, cholangitis episodes and associated anomalies did not show significant correlation; only clearance of jaundice within 6 months was significantly predictive of NLS.

Clinical profile, referral trends, and real-world application of vibration-controlled transient elastography in children with non-alcoholic fatty liver disease in Singapore.

Background and Aim: Pediatric non-alcoholic fatty liver disease (NAFLD) is a progressive disorder that is increasing in incidence globally. The study aims to describe the clinical profile and longitudinal outcome, including the utility of vibration-controlled transient elastography (VCTE), in children with NAFLD at a single tertiary liver unit in Singapore. Methods: Retrospective review of patients aged 0-18 years referred for NAFLD from 2003 to 2020 was conducted. Diagnosis was based on persistent elevation of alanine transaminase ≥2× the upper limit of normal in at-risk patients, and/or radiologic detection of hepatic steatosis, with the exclusion of other etiologies. VCTE-derived liver stiffness measurements (LSMs) ≤7.0 , 7.1-9.0, and ≥9.1 kPa were used to differentiate normal (F0-F1), significant fibrosis (F2), and advanced fibrosis (F3-F4), respectively. Results: The study included 210 patients (72.4% male, mean age 11.6 years). New cases increased from 1.7/1000 referrals in 2003-2008 to 12.7 and 24.5/1000 referrals in 2009-2014 and 2015-2020, respectively. Significant proportion had dyslipidemia (41.4%), impaired glucose tolerance/diabetes (IGT/DM, 26.7%), and hypertension (17.1%). Only 6.2% had resolution of NAFLD after a mean follow-up of 3.7 years. Based on VCTE (n = 65), 41.5% had normal LSM, while 26.2% and 32.3% had increased likelihood of significant and advanced fibrosis, respectively. Age ≥16 years (odds ratio [OR] 8.9), IGT/DM (OR 6.5), and aspartate transaminase >70 U/L (OR 11.0) were independent risk factors associated with increased likelihood of advanced fibrosis. Conclusion: Incidence of pediatric NAFLD has increased dramatically in Singapore. Based on LSM estimation, pediatric NAFLD may be associated with an increased risk of developing advanced fibrosis by late adolescence.

Incidence of intussusception in Singaporean children aged less than 2 years: a hospital-based prospective study.

BACKGROUND: Continuous surveillance for intussusception (IS) is important for monitoring the safety of second-generation rotavirus vaccines. The present study aimed to assess the incidence of IS in Singaporean children aged < 2 years. METHODS: This was a prospective, hospital-based, multi-center surveillance conducted in seven hospitals - two public hospitals and five private medical centers between May 2002 and June 2010 in Singapore. Diagnosis of IS (definite, probable, possible, suspected) was based on the case definition developed by the Brighton Collaboration. Children < 2 years of age who were diagnosed with IS were enrolled in this study. Incidence of IS was calculated per 100,000 child-year with its 95% confidence interval. RESULTS: Of the 178 children enrolled, 167 children with definite IS cases were considered for final analyses; 11 were excluded (six diagnosed as probable IS and four diagnosed as suspected IS; one child's parents withdrew consent). Mean age of children with definite IS was 11.6 ± 6 months; 67.7% were males. The overall incidence of IS was 28.9 (95% CI: 23.0-34.8) and 26.1 (95% CI: 22.2-30.0) per 100,000 child-year in children < 1 year and < 2 years of age, respectively. The majority of IS cases (20 [12.0%]) were reported in children aged 6 months. Most children (98.2% [164/167]) recovered, two (1.2%) children recovered with sequelae and one (0.6%) child died of septic shock. CONCLUSIONS: The incidence of IS remained low and stable in Singaporean children aged < 2 years during the study period (May 2002 to June 2010). TRIAL REGISTRATION: NCT01177839.

Demographics, aetiology and outcome of paediatric acute liver failure in Singapore.

Introduction: The aetiology of paediatric acute liver failure (PALF) varies widely according to age, and geographic and socioeconomic factors. This study aimed to examine the epidemiology, aetiology and outcome of PALF in Singapore at a single centre. Methods: A retrospective review was performed of patients aged 0-18 years who were diagnosed with PALF from 2007 to 2019. PALF was defined by: absence of chronic liver disease; biochemical evidence of acute liver injury; and coagulopathy, non-correctible by vitamin K, defined as prothrombin time (PT) ≥20 seconds or international normalised ratio (INR) ≥2.0 regardless of hepatic encephalopathy (HE) or PT ≥15 seconds or INR ≥1.5 in the presence of HE. Results: 34 patients were included. Median age at diagnosis was 10 months (range 7 days to 156 months). The top three causes of PALF were indeterminate (41.2%), metabolic (26.5%) and infectious (26.5%) aetiologies. A metabolic disorder was the most frequent aetiology in infants <12 months (38.9%), whereas an indeterminate cause was the most common in children >12 months (50%). No cases of viral hepatitis A or B presenting with PALF were detected. Overall spontaneous recovery rate (survival without liver transplantation [LT]) was 38.2%, and overall mortality rate was 47.1%. Six patients underwent living-donor LT, and the post-transplant survival at one year was 83.3%. Conclusion: The aetiologic spectrum of PALF in Singapore is similar to that in developed Western countries, with indeterminate aetiology accounting for the majority. PALF is associated with poor overall survival; hence, timely LT for suitable candidates is critical to improve survival outcomes.

Safety and reactogenicity of DTPa-HBV-IPV/Hib and DTPa-IPV/I-Hib vaccines in a post-marketing surveillance setting.

Combination vaccines have been shown to improve the timeliness of vaccination and vaccine coverage. Safety and reactogenicity of combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib, Infanrix IPV+Hib, GlaxoSmithKline Biologicals) was assessed in two clinical studies. In Study A, 2,590 subjects received DTPa-IPV/Hib at 3, 4 and 5 months of age with a booster at 18 months. In Study B, 702 subjects received the same schedule but with DTPa-hepatitis B-IPV/Hib (DTPa-HBV-IPV/Hib, Infanrix hexa, GlaxoSmithKline Biologicals) vaccine administered at 5 months of age. Reactogenicity was assessed for four days after each dose using diary cards. Serious adverse events (SAEs) were assessed until 24 months of age. The vaccines were well tolerated. After primary vaccination, irritability was the most frequently reported grade 3 general symptom (0.8% of doses in both studies). Fever (axillary) > 39 degrees C was infrequent (0.3% of doses in Study A; 0.5% of doses in Study B). After the booster dose, the most frequently reported grade 3 symptom was redness (5%) in Study A and pain (0.5%) in Study B. An axillary temperature > 39 degrees C was reported in 1.1% of subjects. Throughout the study period, 646 SAEs were reported, of which 6 SAEs were considered to be vaccination-related. The reactogenicity and safety profile of the combined DTPa-IPV/Hib vaccine was good when used for primary and booster vaccinations in over 3,000 Singaporean infants. Substitution of DTPa-IPV/Hib with DTPa-HBV-IPV/Hib at Month 5 reduced the number of injections required at this age by one.

Hepatocellular Carcinoma in the Absence of Cirrhosis in a Child With Inactive Chronic Hepatitis B Infection.

Chronic hepatitis B infection has been identified as an important risk factor for developing hepatocellular carcinoma (HCC) especially in the presence of hepatitis and liver cirrhosis. However, here we describe an unusual case of a child with chronic hepatitis B infection who developed HCC in the absence of active hepatitis or cirrhosis. This case serves to highlight the importance of regular HCC surveillance for all children with chronic hepatitis B, regardless of presence or absence of hepatitis or cirrhosis.

Analysis of Cholangitis Rates with Extended Perioperative Antibiotics and Adjuvant Corticosteroids in Biliary Atresia.

PURPOSE: There is no consensus regarding adjuvant therapies following Kasai portoenterostomy (KP) for biliary atresia (BA). This study aimed to analyze the effect of extended perioperative intravenous antibiotics (PI-Abx) and adjuvant corticosteroid on cholangitis and jaundice clearance rates in the 3 years post-KP in children with BA. METHODS: Data of patients who underwent KP between 1999-2018 at a single center were retrospectively analyzed. Group A (1999-2010) received PI-Abx for 5 days, Group B (2010-2012) received PI-Abx for 5 days plus low-dose prednisolone (2 mg/kg), and Group C (2012-2017) received PI-Abx for 14 days plus high-dose prednisolone (5 mg/kg). RESULTS: Fifty-four patients were included with groups A, B, and C comprising 25, 9, and 20 patients, respectively. The number of episodes of cholangitis was 1.0, 1.6, and 1.3 per patient (p=NS) within the first year and 1.8, 2.3, and 1.7 (p=NS) over 3 years in Groups A, B, and C, respectively. The jaundice clearance rate at 6 months was 52%, 78%, and 50% (p=NS), and the 3-year native liver survival (NLS) rate was 76%, 100%, and 80% (p=NS) in Groups A, B, and C, respectively. A near-significant association was observed between the incidence of cholangitis within the first year and decompensated liver cirrhosis/death at 3 years post KP (p=0.09). Persistence of jaundice at 6 months was significantly associated with decompensated cirrhosis/death at 3 years (p<0.001). CONCLUSION: The extended duration of PI-Abx and adjuvant corticosteroids was not associated with improved rates of cholangitis, jaundice clearance, or NLS in patients with BA.

Somatic genetic rescue of a germline ribosome assembly defect.

Indirect somatic genetic rescue (SGR) of a germline mutation is thought to be rare in inherited Mendelian disorders. Here, we establish that acquired mutations in the EIF6 gene are a frequent mechanism of SGR in Shwachman-Diamond syndrome (SDS), a leukemia predisposition disorder caused by a germline defect in ribosome assembly. Biallelic mutations in the SBDS or EFL1 genes in SDS impair release of the anti-association factor eIF6 from the 60S ribosomal subunit, a key step in the translational activation of ribosomes. Here, we identify diverse mosaic somatic genetic events (point mutations, interstitial deletion, reciprocal chromosomal translocation) in SDS hematopoietic cells that reduce eIF6 expression or disrupt its interaction with the 60S subunit, thereby conferring a selective advantage over non-modified cells. SDS-related somatic EIF6 missense mutations that reduce eIF6 dosage or eIF6 binding to the 60S subunit suppress the defects in ribosome assembly and protein synthesis across multiple SBDS-deficient species including yeast, Dictyostelium and Drosophila. Our data suggest that SGR is a universal phenomenon that may influence the clinical evolution of diverse Mendelian disorders and support eIF6 suppressor mimics as a therapeutic strategy in SDS.

Immunogenicity, reactogenicity and safety of a diphtheria-tetanus-acellular pertussis-inactivated polio and Haemophilus influenzae type b vaccine in a placebo-controlled rotavirus vaccine study.

INTRODUCTION: In recent years, acellular pertussis combination vaccines have facilitated compliance with and coverage of the national immunisation programme in Singapore. This phase-II study (Rota-007) evaluated the immunogenicity, reactogenicity and safety of a DTPa-IPV/Hib combined vaccine when co-administered with a rotavirus vaccine. MATERIALS AND METHODS: A total of 2464 children aged 3 months were vaccinated with DTPa-IPV/Hib together with a randomised 1:3 ratio of either placebo (n=653) or 1 of 3 different formulations of a rotavirus vaccine. Blood samples were collected for immunogenicity analysis 1 month after the third DTPa-IPV/Hib vaccine dose in a subset of subjects (n = 640). Local and general reactogenicity and unsolicited adverse events were recorded during the follow-up after each vaccination. RESULTS: Serological analysis showed >95% response for all antigens in the co-administered DTPa-IPV/Hib vaccine, with no difference between the rotavirus vaccine and placebo groups. No differences in adverse events and reactogenicity were reported in the rotavirus vaccine and placebo groups. Only 0.2% of the subjects reported Grade 3 adverse events. Three subjects (from the vaccine groups) died during the study, which were assessed by the investigators as unrelated to vaccination. No deaths were reported in the placebo group. CONCLUSION: The combined DTPa- IPV/Hib vaccine is safe, well tolerated and highly immunogenic when given alone or coadministered with the rotavirus vaccine for infants in Singapore.

Conjugated hyperbilirubinemia presenting in first fourteen days in term neonates.

AIM: To describe the etiology and characteristics of early-onset conjugated hyperbilirubinemia (ECHB) presenting within 14 d of life in term neonates. METHODS: Retrospective review was performed of term infants up to 28-d-old who presented with conjugated hyperbilirubinemia (CHB) at a tertiary center over a 5-year period from January 2010 to December 2014. CHB is defined as conjugated bilirubin (CB) fraction greater than 15% of total bilirubin and CB greater or equal to 25 µmol/L. ECHB is defined as CHB detected within 14 d of life. "Late-onset" CHB (LCHB) is detected at 15-28 d of life and served as the comparison group. RESULTS: Total of 117 patients were recruited: 65 had ECHB, 52 had LCHB. Neonates with ECHB were more likely to be clinically unwell (80.0% vs 42.3%, P < 0.001) and associated with non-hepatic causes (73.8% vs 44.2%, P = 0.001) compared to LCHB. Multifactorial liver injury (75.0%) and sepsis (17.3%) were the most common causes of ECHB in clinically unwell infants, majority (87.5%) had resolution of CHB with no progression to chronic liver disease. Inborn errors of metabolism were rare (5.8%) but associated with high mortality (100%) in our series. In the subgroup of clinically well infants (n = 13) with ECHB, biliary atresia (BA) was the most common diagnosis (61.5%), all presented initially with normal stools and decline in total bilirubin but with persistent CHB. CONCLUSION: Secondary hepatic injury is the most common reason for ECHB. BA presents with ECHB in well infants without classical symptoms of pale stools and deep jaundice.

Serologic Responses After Hepatitis B Vaccination in Preterm Infants Born to Hepatitis B Surface Antigen-Positive Mothers: Singapore Experience.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends a 4-dose vaccination schedule for preterm low birth weight infants (<2 kg) and a 3-dose vaccination schedule for preterm infants (≥2 kg) born to hepatitis B surface antigen (HBsAg)-positive mothers. However, data remain limited for these high-risk infants, and the optimal dosing schedule in Asia is not well established. AIM: The aim of this study was to evaluate the serologic vaccine responses in preterm infants born to HBsAg-positive mothers using current vaccination guidelines. METHODS: Preterm babies of gestation less than 37 completed weeks born to HBsAg-positive mothers were prospectively recruited during 6 years (June 2009 to December 2015) and retrospectively recruited via convenience sampling in 2 years (June 2013 to April 2015) in 2 tertiary pediatric centers. The preterm infants were given 4 or 3 vaccine doses as per ACIP 2005 guidelines. Vaccine response was defined as achieving hepatitis B surface antibody values of >10 IU/L [Abbott Architect (Abbott Laboratories, Chicago, IL)] at 9 months of chronologic age. RESULTS: A total of 24 preterm infants were recruited. Four had a birth weight <2 kg. Of 23 surviving infants, all were negative for HBsAg. One baby (4.5%) did not achieve adequate vaccine response. All 4 infants with birth weight <2 kg achieved seroprotective values. CONCLUSION: The current ACIP-recommended vaccination schedule results in adequate antibody responses in preterm infants of HBsAg-positive mothers.

The epidemiology of paediatric intussusception in Singapore: 1997 to 2004.

INTRODUCTION: The world's first rotavirus vaccine, Rotashield or RRV-TV, was registered in the US in 1998, but withdrawn within a year because of an observed association with intussusception (IS). Surveillance for IS has consequently become important in safety monitoring of new-generation rotavirus vaccines during development. Post-marketing surveillance is also important, and requires the availability of local baseline epidemiology data on IS. MATERIALS AND METHODS: An eight-year study of IS in children under 2 years of age in Singapore was performed by retrospective review of admissions to KK Women's and Children's Hospital, the main paediatric hospital, from 1997 to 2001, followed by prospective surveillance of all hospitals from 2001 to 2004, using the case definition of the Brighton Collaboration Intussusception Working Group. RESULTS: The average IS incidence was 60 per 100,000 in under-ones, and 32 per 100,000 in under-twos, with a downward trend between 1999 and 2004. Ninety-two per cent of subjects were aged below one year, with 51% aged 6 months to 11 months. The mean age at which IS occurred increased from 6.4 months to 12.5 months over the study period. The male-to-female ratio was 1.3:1. No trend in IS numbers was observed over different months of the year. CONCLUSION: IS in Singapore shows no seasonality, but has demonstrated a trend of decreasing incidence in recent years. While highest in the first year of life, the risk of IS is increasing in the second year of life. Males have a slightly higher risk.

Efficacy, Immunogenicity and Safety of a Human Rotavirus Vaccine RIX4414 in Singaporean Infants.

INTRODUCTION: This was the first study conducted to evaluate the efficacy of 2 oral doses of the human rotavirus vaccine, RIX4414 in Singaporean infants during the first 3 years of life. MATERIALS AND METHODS: Healthy infants, 11 to 17 weeks of age were enrolled in this randomised (1:1), double-blinded, placebo-controlled study to receive 2 oral doses of RIX4414 vaccine/placebo following a 0-, 1-month schedule. Vaccine efficacy against severe rotavirus (RV) gastroenteritis (Vesikari score ≥11) caused by wild-type RV strains from a period starting from 2 weeks post-Dose 2 until 2 and 3 years of age was calculated with 95% confidence interval (CI). Immunogenicity and safety of the vaccine were also assessed. RESULTS: Of 6542 infants enrolled, 6466 were included in the efficacy analysis and a subset of 100 infants was included in the immunogenicity analysis. Fewer severe RV gastroenteritis episodes were reported in the RIX4414 group when compared to placebo at both 2 and 3 year follow-up periods. Vaccine efficacy against severe RV gastroenteritis at the respective time points were 93.8% (95% CI, 59.9 to 99.9) and 95.2% (95% CI, 70.5 to 99.9). One to 2 months post-Dose 2 of RIX4414, 97.5% (95% CI, 86.8 to 99.9) of infants seroconverted for anti-RV IgA antibodies. The number of serious adverse events recorded from Dose 1 until 3 years of age was similar in both groups. CONCLUSION: Two oral doses of RIX4414 vaccine was immunogenic and provided high level of protection against severe RV gastroenteritis in Singaporean children, during the first 3 years of life when the disease burden is highest.

Incidence of rotavirus gastroenteritis by age in African, Asian and European children: Relevance for timing of rotavirus vaccination.

Variability in rotavirus gastroenteritis (RVGE) epidemiology can influence the optimal vaccination schedule. We evaluated regional trends in the age of RVGE episodes in low- to middle- versus high-income countries in three continents. We undertook a post-hoc analysis based on efficacy trials of a human rotavirus vaccine (HRV; Rotarix™, GSK Vaccines), in which 1348, 1641, and 5250 healthy infants received a placebo in Europe (NCT00140686), Africa (NCT00241644), and Asia (NCT00197210, NCT00329745). Incidence of any/severe RVGE by age at onset was evaluated by active surveillance over the first two years of life. Severity of RVGE episodes was assessed using the Vesikari-scale. The incidence of any RVGE in Africa was higher than in Europe during the first year of life (≤2.78% vs. ≤2.03% per month), but much lower during the second one (≤0.86% versus ≤2.00% per month). The incidence of severe RVGE in Africa was slightly lower than in Europe during the first year of life. Nevertheless, temporal profiles for the incidence of severe RVGE in Africa and Europe during the first (≤1.00% and ≤1.23% per month) and second (≤0.53% and ≤1.13% per month) years of life were similar to those of any RVGE. Any/severe RVGE incidences peaked at younger ages in Africa vs. Europe. In high-income Asian regions, severe RVGE incidence (≤0.31% per month) remained low during the study. The burden of any RVGE was higher earlier in life in children from low- to middle- compared with high-income countries. Differing rotavirus vaccine schedules are likely warranted to maximize protection in different settings.

Prolonged hepatitis and jaundice: a rare complication of paediatric Epstein-Barr virus infection.

We herein report the case of a 14-year-old girl with Epstein-Barr virus (EBV) infectious mononucleosis who developed prolonged hepatitis and jaundice. At presentation, she had tender hepatomegaly with a markedly deranged liver function test. Abdominal ultrasonography showed hepatomegaly and a thickened gallbladder wall. During the subsequent 11 weeks, her transaminases showed two further peaks, which corresponded with clinical deterioration. Her highest alanine transaminase level was 1,795 µ/L and total bilirubin level was 154 µmol/L. She recovered fully with conservative management. EBV-related liver involvement is typically mild and self-limiting. We believe that tender hepatomegaly and gallbladder thickening may be important predictors of significant liver involvement. Although multiple transaminase peaks may occur, we do not consider this an indication for antiviral or immunosuppressive therapy. In the absence of strong evidence supporting the use of any specific therapy, we recommend a conservative approach for an immunocompetent patient.

A rotavirus vaccine for prophylaxis of infants against rotavirus gastroenteritis.

The need for safe and effective vaccines to reduce morbidity and mortality caused by rotavirus gastroenteritis in children is well-known. A live attenuated monovalent rotavirus vaccine (Rotarix) containing human rotavirus strain RIX4414 of G1P1A P[8] specificity is being developed to meet the global need. An overview of RIX4414 trials in developed and developing settings is presented for 3 selected trials conducted in Finland (pilot study), Latin America (Brazil, Mexico and Venezuela) and Singapore involving 5024 infants. The vaccine was well-tolerated, with no increase in any solicited symptoms as compared with the placebo. After 2 doses, 61-91% of vaccinated infants developed rotavirus-specific IgA antibodies. There was no interference with immunogenicity of coadministered routine pediatric vaccines. Rotarix significantly reduced rotavirus gastroenteritis episodes and rotavirus-related hospitalizations in vaccinated infants compared with placebo recipients (P < 0.05). Vaccine efficacy was observed against severe rotavirus gastroenteritis caused by G1 and non-G1 types including the emerging G9 type (P < 0.05) in Latin America. These results show prospects for widespread use of Rotarix to reduce rotavirus disease burden and warrant continued worldwide evaluation.

Paediatric inflammatory bowel disease in a multiracial Asian country.

INTRODUCTION: This study examined the characteristics and trends in the incidence of inflammatory bowel disease (IBD) among children in Singapore. METHODS: We retrospectively reviewed all patients under 18 years diagnosed with IBD over a 14-year period. Information on demographics, disease presentation, laboratory findings, radiological investigations, and endoscopic and histological findings were obtained from the patients' medical records. RESULTS: 32 patients were diagnosed with IBD, 30 of whom had Crohn's disease and 2 had ulcerative colitis. The incidence of IBD rose from an initial rate of 2.2 per 100,000 patients in the year 2000 to a peak of 11.4 patients per 100,000 patients by 2008. Median age of onset of symptoms was 10.5 years. There were more boys (63%) than girls in the group and a higher representation of Indians (34.4%). The most common presenting symptoms were abdominal pain (87.5%), diarrhoea (75.0%) and weight loss (71.9%). Extraintestinal manifestations such as fever and arthralgia were found in over 50% of patients. The most common physical findings were perianal abnormalities (56.3%), mouth ulcers (37.5%) and growth failure (15.6%). Abnormal laboratory findings such as low albumin, raised erythrocyte sedimentation rate, anaemia, thrombocytosis and high C-reactive protein were found in nearly half of the patients. Endoscopic and histological findings showed that a majority of patients (90.6%) also had evidence of inflammation in the upper gastrointestinal tract. CONCLUSION: Paediatric IBD is on the rise. The higher occurrence in Indians, earlier onset and more florid presentation may suggest different genetic and environmental influences specific to Asian children.