Shwachman-Diamond Syndrome: Are we Missing Many.

Shwachman-Diamond Syndrome (SDS) is a rare inherited disorder characterized by pancreatic insufficiency, bone marrow dysfunction and skeletal abnormalities. It is the most common cause of pancreatic insufficiency in children after cystic fibrosis. We report a child with classical SDS who presented to us predominantly with chronic diarrhea along with delayed growth and neutropenia.

Factor V Leiden and prothrombin gene G20210A mutations are uncommon in portal vein thrombosis in India.

BACKGROUND: Extra-hepatic portal vein obstruction due to portal vein thrombosis (PVT) is an important cause of portal hypertension in several regions including India. The cause of thrombosis in these patients remains unclear. We studied the frequency of mutations in genes for coagulation factors V and II (prothrombin) in 61 Indian patients with PVT and 49 healthy control subjects. METHODS: The presence of factor V Leiden mutation and of G20210A prothrombin gene mutation was determined using polymerase chain reaction followed by restriction fragment length polymorphism. Chi-squared test was used to compare patients and controls. RESULTS: Of the 61 patients (median age 11 years; 47 male) studied, 49 were children. One of 61 (1.6%) patients with PVT was heterozygous for factor V Leiden mutation and none had the G20210 prothrombin gene mutation. The frequencies of these mutations were not different from those in control subjects (2/49 and 0/46, respectively). CONCLUSION: Factor V Leiden and G20210 prothrombin gene mutations are infrequent in Indian patients with PVT. Thus, these mutations are unlikely to be responsible for PVT in the Indian population.

Management of portal hypertension.

Portal hypertension (PHT) is common in children and a majority of cases in India are constituted by extrahepatic portal venous obstruction or cirrhosis of liver. Morbidity and mortality in this condition is related to variceal bleeding, most commonly from esophageal varices. Acute variceal bleeding is best controlled by endoscopic therapy. Somatostatin and octreotide are useful in acute variceal bleeding as a supplementary therapy. Acute variceal bleeding uncontrolled by medical therapy merits preferably a shunt surgery or devascularization depending upon etiology of PHT and expertise of the surgeon. Acute variceal bleeding originating from gastric varices can be effectively controlled by endoscopic injection of tissue adhesive agent (n-butyl 2 cyanoacrylate). Eradication of esophageal varices by endoscopic measures (sclerotherapy or band ligation) is successful in prevention of recurrence of bleeding. Surgical portosystemic shunts especially in non-cirrhotic PHT are successful in achieving portal decompression and significant reduction in recurrence of variceal bleeding. Role of beta-blockers in primary prophylaxis of variceal bleeding in children still remains to be substantiated.

Coeliac disease in Indian children: assessment of clinical, nutritional and pathologic characteristics.

Coeliac disease is an important cause of chronic diarrhoea, failure to thrive, and anaemia in children. Little information on the disease is available in India. This study was undertaken to determine the prevalence, clinical, anthropometric and histological profiles of coeliac disease in patients attending a tertiary referral centre in India. Coeliac disease was diagnosed in 42 (16.6%) of 246 children with chronic diarrhoea, failure to thrive, and anaemia. The mean ages at onset of symptoms and at diagnosis were 2.4 (range 0.5-10) years and 8.3 (range 3-14) years respectively, and a mean period of delay in diagnosis was 5.9 (range 1-13.5) years. Of the 42 cases, history of failure to thrive was observed in 38 (90%), chronic diarrhoea in 37 (88%), and anaemia in 6 cases. Short stature, under-nutrition, anaemia, oedema of feet, rickets, clubbing of fingers, features of vitamin A deficiency, and B-vitamin deficiency were found in 42, 26, 38, 9, 8, 6, 3, and 2 cases respectively. Onset of symptoms, such as, chronic diarrhoea and failure to thrive, was earlier in children with subtotal villous atrophy than in those with partial villous atrophy (mean +/- SD; 2.00 +/- 1.46 years vs 3.30 +/- 2.72 years; p < 0.05). Results of the study suggest that coeliac disease is not uncommon in Indian children. Coeliac disease should be considered in the differential diagnosis, particularly in children without any symptoms of diarrhoea.

Functional protein C and anti-cardiolipin antibody in children with portal vein thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) is a common cause of portal hypertension in children from developing countries. Deficiencies of proteins C and S and elevated anticardiolipin antibody (aCL) levels have been shown to predispose to venous thrombosis. We studied these factors in children with idiopathic PVT. METHODS: 19 children with PVT (mean [SD] age 5.7 [2.1] y; 15 boys) were studied; all had had variceal bleeding, and had PVT on ultrasonography. Functional protein C activity was measured using a clotting assay; if it was normal, a clotting assay for functional protein S activity was performed. IgG aCL levels were measured in all sera using an in-house standardized solid-phase ELISA. RESULTS: Protein C functional activity ranged from 4% to 109%. Eight children had activity below 70%, the lower cut-off of the normal range. Protein S assay, done in 10 of the 11 children with normal protein C activity levels, was normal (above the cut-off level of 65% of the normal range). IgG aCL levels were abnormally elevated (>mean + 2SD of 16 healthy control children) in nine children; of these, three had associated protein C deficiency. Thus, of the 19 children with idiopathic PVT, 14 had abnormality in one or more tests. CONCLUSION: A majority of children with PVT of unknown etiology have functional protein C deficiency or abnormally elevated levels of aCL antibodies.

Neonatal cholestasis syndrome: Indian scene.

Neonatal cholestasis syndrome (NCS) in India has largely remained ignored. Three questions need to be addressed: (a) What is known about NCS in India (b) Where do we stand and (c) What needs to be done? Current data on etiology of NCS indicates that biliary atresia contributes to about 40% of all NCS cases. There is considerable delay in the referral of patients to appropriate centres for management. A delay of 120.8 +/- 60.5 days in biliary atresia and 65.9 +/- 39.2 days in neonatal hepatitis were documented. Biliary atresia cases need to be diagnosed and operated by eight weeks of age so as to have the best results. Delayed referral after 3 months of age, not only bring down the success rate considerably but also adversely affect the management with regard to surgical procedures, nutritional support, control of ascites and finally the cost. Cirrhosis rapidly develops in children with biliary atresia. At this stage the only option left is liver transplantation. An important obstacle in the care of infants with NCS is the misconception of jaundice in newborns. This needs to be handled at a professional level in the training of undergraduates and postgraduates and the lay public. Public awareness campaigns like "Yellow Alert" may be useful in this direction.

Need for liver transplantation in Indian children.

BACKGROUND: Liver transplantation (LT) is the most successful and accepted mode of therapy for failing liver in children. Pediatric LT has neither been widely attempted nor its need objectively assessed in our country. OBJECTIVE: To assess requirement of LT in children at a tertiary care hospital. METHODS: Data of children admitted to pediatric GE services (January 1992 to June 1997) were retrospectively analyzed. Subgroups of children with acute liver disease (ALD), chronic liver disease (CLD), neonatal cholestasis syndrome (NCS) and other etiology were evaluated for need for LT according to established criteria. RESULTS: Of the total 301 inpatients with liver diseases assessed at our center, ALD constituted 26% (n=79), CLD 35% (n=106), NCS 27% (n=82) and miscellaneous 11% (n=34). Among ALD, 19% (n=15) had FHF and 67% (n=10) qualified for LT (INR>4.0). Of CLD, LT was warranted in 13% (2/15) cases of Wilson's disease (Wilson's score > 6) and 60% of cirrhotics (n=40/66) with decompensation. NCS comprised extrahepatic biliary atresia (EHBA) in 43, choledochal cyst in 2, paucity of intralobular bile duct (PILBD) in 2, neonatal hepatitis in 23, and was of indeterminate etiology in 12 cases. Of NCS groups, LT was the only therapeutic option in 45% (n=36) of cases (EHBA 34, choledochal cyst 2). Of 34 cases of EHBA requiring LT, 32 presented after 4 months of age and other 2 children had decompensation before four months of age. Both children with choledochal cysts had decompensated liver disease. One patient of Crigler Najjar syndrome type I had kernicterus and qualified for LT. CONCLUSION: Our data shows need for LT in 30% of children with liver diseases constituted by cirrhosis (45%), biliary atresia (38%) and FHF (11%).

Current spectrum of hepatobiliary disorders in northern India.

OBJECTIVE: To evaluate the current spectrum of hepatobiliary disorders in children in Northern India. SETTING: Tertiary level referral hospital. METHODS: All children with hepatobiliary disorders presenting between January 1992 through July 1995 were evaluated by clinical assessment, liver function tests, viral and autoimmune markers, liver biopsy, copper studies and other relevant investigations. RESULTS: Two hundred and thirty five children with hepatobiliary disorders were seen over three and a half years period (67 cases per year). Acute hepatitis (28%), chronic liver disease (36%) and neonatal cholestasis syndrome (NCS) (26%) were the most common patterns of liver diseases. Chronic liver diseases were constituted by ICC (2%), post-hepatitic etiology (13%), Wilson's disease (21%), autoimmune (4%), non-Wilsonian metabolic diseases (16%), hepatic venous outflow obstruction (2%) and non-cirrhotic portal fibrosis (1%). Cirrhosis was documented in 71% and chronic hepatitis in 12% of cases with chronic liver disease. Fulminant hepatic failure was the presentation in 4% of children with liver diseases. CONCLUSION: Chronic liver diseases in Northern India are mainly constituted by post hepatitic, metabolic and cryptogenic etiology and ICC is rarely encountered. NCS is also one of the major subgroups of liver diseases in children.

Endoscopic, histologic and microbiologic evaluation of upper abdominal pain with special reference to Helicobacter pylori infection.

OBJECTIVE: To study children with significant upper abdominal pain of unidentifiable etiology and evaluate: (a) the relationship of pain to inflammatory esophago-gastro-duodenal lesions and Helicobacter pylori (HP) infection, and (b) the response to specific therapy. DESIGN: Prospective study. SETTING: Pediatric section of a tertiary referral gastroenterology center. SUBJECTS: Thirty three consecutive children with significant upper abdominal pain [mean age 9.9 +/- 2.7, range 4-15 years; 20 males] were subjected to upper gastrointestinal tract endoscopy and antral mucosal biopsies obtained for rapid urease test (RUT), Gram's staining of impression/crush smears and culture for HP and histologic examination. Patients with HP gastritis were treated with triple therapy, colloidal bismuth subcitrate, amoxycillin and metronidazole, for two weeks. At 8 weeks from the initiation of therapy, patients were re-evaluated for symptoms and HP eradication by repeat endoscopy and antral biopsies. Patients with esophagitis, gastritis and duodenitis without HP infection were treated with ranitidine for 6 weeks. All the patients were followed up for 6 months. RESULTS: Histology revealed antral gastritis in 28/33 (85%) patients. HP infection was present in 12/28 (43%) patients with antral gastritis. Symptomatic improvement with triple therapy was observed in 10/12 (83%) patients with HP gastritis and eradication of HP in 5/7. Improvement on ranitidine therapy was observed in 12/16 (75%) patients with HP negative gastritis. On follow-up, no patient with initial improvement with therapy had relapse of symptoms. CONCLUSION: Symptomatic children with HP related gastritis should be treated with triple therapy and HP negative gastritis with H2-receptor antagonist.

Therapeutic gastrointestinal endoscopy.

The safety, efficacy and utility of various therapeutic gastrointestinal (GI) endoscopic procedures performed on children (January 1992 to July 1995) at a tertiary referral centre in India were studied. A total of 1,030 sessions (upper GI 972 and lower GI 58) of therapeutic GI endoscopy were performed in 162 children (mean age 7.4 +/- 4 years; upper GI 115, lower GI 47). Various upper GI endoscopic procedures done were injection sclerotherapy (EIS), endoscopic variceal ligation (EVL), bougie dilatation of oesophageal strictures, balloon dilatations of oesophageal stricture/pyloric obstruction and retrieval of foreign bodies in 75%, 6%, 9%, 4% and 12% of children respectively. Therapy for bleeding from oesophageal varices constituted the major group (75%). Repeated EIS (sessions total--876, mean 8, range 5-15) performed on 86 children resulted in control of bleeding in all and eradication of oesophageal varices in 85% of cases. Minor complications (oesophageal ulcers and oesophageal strictures) due to EIS were observed in 9% of children. EVL (10 sessions in 7 children) was effective in controlling bleeding and substantial decrease of varices in all without any complication. Oesophageal dilation either by bougie (61 sessions in 10 children) or balloon (6 sessions in 3 children) were performed for benign strictures. Balloon dilatation of pyloric obstruction was successfully done in 2 children. Foreign bodies (retained or sharp) were retrieved from upper GI tract in 14 children. No complications were observed with stricture dilatation/foreign body retrieval. Therapeutic lower GI endoscopies were performed in 47 children (colonoscopic polypectomy in 92%, anal dilatation and piles banding in 4% each). One child with juvenile polyposis coli developed sigmoid colon performation following colonoscopic polypectomy which required surgical correction. We conclude that upper and lower GI endoscopic therapeutic procedures in children are highly effective and safe. The risk of major complication is very small in experienced hands and occasional minor complications, can be managed conservatively.

Neonatal cholestasis syndrome: an appraisal at a tertiary center.

OBJECTIVE: To know the magnitude, etiology and clinical profile, the efficacy of various investigations and the outcome in patients with neonatal cholestasis syndrome (NCS). DESIGN: Prospective evaluation of 60 consecutive infants with NCS (mean age 3.9 +/- 1.9 months; 49 males) over a period of 3.5 years. SETTING: Tertiary level referral gastroenterology center in North India. METHODS: Liver function tests, urine examination, serum antibodies against Cytomegalovirus (CMV), Rubella and Toxoplasma; abdominal ultrasonography, hepatobiliary scintigraphy and liver biopsy were done. In appropriate setting, laparotomy and surgical corrections were done for biliary tract disorders. RESULTS: NCS constituted 19% of pediatric liver diseases. Considerable delay in presentation was observed [mean delay, extrahepatic biliary atresia (EHBA) = 4 +/- 2.0 months, neonatal hepatitis (NH) = 2.2 +/- 1.3 months]. Thirty three (55%) infants had EHBA, 14 (23%) NH (4 CMV, 2 galactosemia, 1 urinary tract infection and 7 idiopathic), 2 (3%) paucity of intralobular bile ducts and 11 (18%) were of indeterminate etiology. Liver biopsy was the most accurate (96.4%) investigation in discriminating between EHBA and NH. Of the 18 operated infants with EHBA (portoenterostomy-15 and hepatico-jejunostomy-3), 10 were alive (mean follow up = 22.8 +/- 8.6 months) of which 4 were completely asymptomatic. CONCLUSIONS: (i) NCS is an important cause of liver disease in Indian children. (ii) It requires prompt referral, quick investigative approach and targeted management. (iii) Liver biopsy is highly accurate in differentiating EHBA and NH. (iv) infants with EHBA and compensated status of liver should undergo corrective surgery irrespective of age at presentation.

Healing of chronic antral gastritis: effect of sucralfate and colloidal bismuth subcitrate.

BACKGROUND: Colloidal bismuth subcitrate (CBS) causes endoscopic and histological improvement in gastritis and eradication of Helicobacter pylori in patients with non-ulcer dyspepsia (NUD). The effect of sucralfate, a cytoprotective drug, on endoscopic and histologic gastritis and H pylori clearance is not clear. We studied the effect of CBS and sucralfate on these features in patients with NUD. METHODS: Sixty three patients with NUD and H pylori infection were randomized to receive one of the following for four weeks: (i) CBS (240 mg twice daily) (Group 1); (ii) placebo I, similar in size, color and shape to CBS (Group 2); (iii) sucralfate (2.0 g twice daily) (Group 3) and (iv) placebo II, similar to sucralfate (Group 4). Symptoms, endoscopic and histological findings and H pylori status were assessed before and after treatment. RESULTS: Similar symptomatic improvement was observed with each treatment, indicating a placebo effect. Significant endoscopic and histological improvement was observed with CBS only. CBS was better than sucralfate in inducing endoscopic and histological improvement. Clearance rate of H pylori was 46.6% with CBS, 16.6% with its placebo, 33.3% with sucralfate and 13.3% with its placebo. CONCLUSION: CBS is more effective than sucralfate in inducing endoscopic and histologic healing of H pylori-related gastritis among NUD patients.