Christina Ong

Tricho-hepato-enteric syndrome (THE-S): two cases and review of the literature

AbstractTricho-hepato-enteric syndrome (THE-S) is characterized by severe infantile diarrhea, failure to thrive, dysmorphism, woolly hair, and immune or hepatic dysfunction. We report two cases of East Asian descent with THE-S who had remained undiagnosed despite extensive investigations but were diagnosed on whole exome sequencing (WES). Both cases presented with chronic diarrhea, failure to thrive, and recurrent infections. Case 1 had posteriorly rotated low set ears, mild retrognathia, and fine curly hypopigmented hair. She was managed with prolonged total parenteral nutrition and intravenous immunoglobulin infusions. Case 2 had sparse coarse brown hair as well as multiple lentigines and café-au-lait macules. She was managed with amino acid-based formula. For both cases, routine investigations were inconclusive. WES in both cases showed biallelic truncating mutations in TTC37 (c.3507T>G;p.Y1169X and c.3601C>T;p.R1201X in case 1 and c.3507T>G;p.Y1169X and c.154G>T;p.E52X in case 2), suggesting a diagnosis of THE-S. Conclusion: We present novel mutations in the TTC37 gene in two individuals of East Asian descent with the rare THE-S, detected by WES. Future identification of patients with THE-S and establishing genotype-phenotype correlations will aid in counseling the patients and their families.What is Known:• Tricho-Hepato-Enteric syndrome (THE-S) is characterized by severe infantile diarrhea, failure to thrive, dysmorphism, woolly hair, and immune or hepatic dysfunction.• Complex patients with diagnostic dilemmas undergo extensive investigations.What is New:• This is a report of novel mutations in TTC37 in individuals of East Asian descent.• Whole exome sequencing (WES) can be useful in certain complex cases with diagnostic dilemmas.

Cap polyposis: A rare cause of rectal bleeding in children

AIM To evaluate the clinicopathological features and treatment outcomes of cap polyposis in the pediatric population. METHODS All pediatric patients with histologically proven diagnosis of cap polyposis were identified from our endoscopy and histology database over a 12 year period from 2000-2012 at our tertiary pediatric center, KK Womens and Childrens Hospital in Singapore. The case records of these patients were retrospectively reviewed. The demographics, clinical course, laboratory results, endoscopic and histopathological features, treatments, and outcomes were analyzed. The study protocol was approved by the hospital institutional review board. The histological slides were reviewed by a pediatric histopathologist to confirm the diagnosis of cap polyposis. RESULTS Eleven patients were diagnosed with cap polyposis. The median patient age was 13 years (range 5-17 years); the sample included 7 males and 4 females. All of the patients presented with bloody stools. Seven patients (63%) had constipation, while 4 patients (36%) had diarrhea. All of the patients underwent colonoscopy and polypectomies (excluding 1 patient who refused polypectomy). The macroscopic findings were of polypoid lesions covered by fibrinopurulent exudates with normal intervening mucosa. The rectum was the most common involvement site (n = 9, 82%), followed by the rectosigmoid colon (n = 3, 18%). Five (45%) patients had fewer than 5 polyps, and 6 patients (65%) had multiple polyps. Histological examination of these polyps showed surface ulcerations with a cap of fibrin inflammatory exudate. Four (80%) patients with fewer than 5 polyps had complete resolution of symptoms following the polypectomy. One patient who did not consent to the polypectomy had resolution of symptoms after being treated with sulphasalazine. All 6 patients with multiple polyps experienced recurrence of bloody stools on follow-up (mean = 28 mo). CONCLUSION Cap polyposis is a rare and under-recognised cause of rectal bleeding in children. Our study has characterized the disease phenotype and treatment outcomes in a pediatric cohort.

Risk of Major Abdominal Surgery in an Asian Population-based Crohnʼs Disease Cohort

Background:Crohns disease (CD) is increasing in incidence and prevalence in Asia, but there is a paucity of population-based studies on risk factors for surgery in Asian patients with CD. This will be useful to identify patients who may benefit from top-down treatment. This study describes the rates of abdominal surgery and identifies associated risk factors in Singaporean patients with CD. Methods:This was a retrospective observational study. The medical records of Singaporeans diagnosed with CD from 1970 to 2013 were reviewed from 8 different hospitals in Singapore. The cumulative probability of CD-related abdominal surgery was estimated using the Kaplan–Meier method. The logistic regression model was used to assess associations between independent risk factors and surgery. Results:The cohort of 430 Singaporean patients with CD included 63.5% Chinese, 11.9% Malay, and 24.7% Indians, with a male to female ratio of 1.6; median follow-up was 7.3 years (range, 2.9–13.0 yr) and median age at diagnosis 30.5 years (range, 19.5–43.7 yr). One hundred twelve patients (26.0%) required major abdominal surgery: the cumulative risk of surgery was 14.9% at 90 days, 21.2% at 5 years, 28.8% at 10 years, 38.3% at 20 years, and 50.6% at 30 years from diagnosis. Of the surgical patients, 75.0% were Chinese, 10.7% Malays, and 14.3% Indians; 21.4% underwent surgery for inflammatory disease, 40.2% for stricturing disease, and 38.4% for penetrating disease. Age at diagnosis (A2 17–40 yr, OR: 2.75, 95% confidence interval [CI], 1.14–7.76), ileal disease (L1 location, OR: 2.35, 95% CI, 1.14–5.0), stricturing (B2 OR: 6.09, 95% CI, 3.20–11.8), and penetrating behavior (B3 OR: 21.6, 95% CI, 9.0–58.8) were independent risk factors for CD-related abdominal surgery. Indian patients were less likely to require surgery (OR: 0.40, 95% CI, 0.19–0.78). Conclusions:Age at diagnosis, L1 location, B2, and B3 disease behavior are independent risk factors for abdominal surgery. Interestingly, despite a higher prevalence of CD in Indians, a smaller proportion of Indian patients required surgery. These findings suggest that both environmental and genetic factors contribute to the risk of surgery in Asian patients with CD.

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

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.

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.

Annular pancreas: a rare cause of upper gastrointestinal bleeding in a child.

A nnular pancreas (AP) is a rare congenital anomaly consisting of a ring of pancreatic tissue partially or completely encircling the second part of the duodenum (1). Most cases are diagnosed in the neonatal period with symptoms of gastric outlet obstruction. We report an unusual case of AP presenting with acute upper gastrointestinal (GI) bleeding in a child. A 12-year-old boy of Malay origin presented with a 1-day history of sudden onset of hematemesis and passing malaenic stools. Before presentation, he had a 1-year history of intermittent postprandial abdominal bloatedness with mild epigastric pain and rare episode of nonbilious vomiting. He tolerated his meals well and showed normal growth along the 75th percentile for both height and weight. Physical examination revealed a pale boy with clinical evidence of hypovolemic shock. He had epigastric tenderness and per rectal examination revealed malaenic stools. The abdomen was not distended and the rest of the physical examination was normal. He required fluid resuscitation to stabilize his vital parameters and was commenced on intravenous omeprazole infusion. Empirical triple therapy for Helicobacter pylori infection comprising amoxicillin, metronidazole, and omeprazole was also started. Initial blood tests showed hemoglobin of 12.6 g/dL (normal 9–14), which dropped to 10.4 g/dL the following day, subsequent to that hemoglobin was stable. Coagulation profile, liver function test, C-reactive protein, and amylase were normal. His GI bleeding resolved within 48 hours with conservative management. Upper GI endoscopy performed on day 3 showed severe gastric erythema at the gastric antrum with a 3-mm irregularly shaped healing ulcer. The stomach antrum and the first part of duodenum (D1) were markedly dilated with stenosis at the junction of second and third part of duodenum (D2-D3). Duodenal mucosa was slightly erythematous with no ulceration (Fig. 1). Histology of the mucosa showed chronic gastritis and mild reflux esophagitis with no evidence of H pylori. The initial clinical impression was duodenal stenosis caused by extrinsic compression or a duodenal web. Magnetic resonance imaging of the abdomen was suggestive

Evidence for Low Residue Diet in the Management of Gastrointestinal Related Conditions

The low residue diet is commonly recommended for pre-colonoscopy bowel preparation as well as in the management of some gastrointestinal conditions including inflammatory bowel disease. There is no objective measurement for residue, resulting in poor standardisation of a low residue diet. This review examines the efficacy of a low residue diet in the management of gastrointestinal conditions. A literature search was conducted in Medline and the Cochrane Library, and eight randomised controlled trials with human subjects met the inclusion criteria. Six studied the low residue diet for pre-colonoscopy bowel preparation, the other two were conducted in Crohns disease and post-gynaecological surgery, respectively. The low residue diet was comparable to the clear liquid diet for bowel preparation without increased side-effects. Post-gynaecological surgery, early feeding using low residue diet decreased nausea without increasing gastrointestinal symptoms when compared to the traditional feeding method. There was limited evidence on the advantage of a low residue diet over a normal diet in the management of acute, non-stenosing Crohns disease. More rigorous studies are required to evaluate the efficacy of the low residue diet for the management of gastrointestinal conditions. In addition, substituting a low residue diet with a low fibre diet would be a more measurable and objective method to standardise guidelines both for research and therapy.

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.

Consensus and contentious statements on the use of probiotics in clinical practice: A south east Asian gastro-neuro motility association working team report: Consensus contentious probiotic clinical use

The concept of consuming microorganisms in the treatment of a medical condition and in health maintenance has gained much attraction, giving rise to an abundance of medical claims and of health supplements. This study identified relevant clinical questions on the therapeutic use of probiotics and reviewed the literature in irritable bowel syndrome, inflammatory bowel disease, impaired intestinal immunity, liver disease, intestinal infections, and common childhood digestive disorders. Statements were developed to address these clinical questions. A panel of experienced clinicians was tasked to critically evaluate and debate the available data. Both consensus and contentious statements are presented to provide to clinicians a perspective on the potential of probiotics and importantly their limitations.