Clinical Vignette Abstracts

Poster Session I Thursday, November 12, 2009

Cellular/Molecular Biology cv 1 EXTREME PHENOTYPIC DIVERSITY OF TYPE 1 GAUCHER DISEASE IN AFFECTED SIBLING‐PAIR: POSSIBLE ROLE OF SUBSTRATE FLUX Philip B. Stein1, Eduardo Zambrano3, Robert Brown2, Mei Yang1, Diana Beardsley2, Pramod K. Mistry1 1Pediatric GI/, Yale New Haven Hospital, New Haven, CT; 2Pediatric Hematology/Oncology, Yale New Haven Hospital, New Haven, CT; 3Pathology, Yale New Haven Hospital, New Haven, CT Type 1 Gaucher disease(GD1) is due to an inherited deficiency of lysosomal glucocerebrosidase (GBA1) leading to systemic build up of its substrate. This results in a heterogenous phenotype. GD1 exhibits remarkable phenotypic diversity and progression patterns among patients harboring the same GBA1 genotypes as well as among affected sib‐pairs. We report a pair of Hispanic siblings with Neurofibromatosis and GD1. One with symptomatic GD1 in the setting of concurrent T cell lymphoma and another who remains asymptomatic from her GD1. Case Report: A 6 year‐old girl presented with lymphadenopathy, bone pain, and hepatosplenomegaly. A T cell acute lymphoblastic lymphoma diagnosis was established; she received chemotherapy with excellent initial response. In evaluation for the extent of her lymphoma, a bone marrow biopsy revealed large numbers of abnormal histiocytes consistent with Gaucher or pseudo‐Gaucher cells. GD1 was confirmed with low glucosidase activity. Baseline investigations revealed hepatosplenomegaly on MRI and dramatic elevation of GD1 serum biomarkers. The patient was treated with replacement therapy. There was an impressive reversal of disease manifestations and biomarkers. Concomitantly, a reducation of bone marrow infiltration was seen. The proband's sister was screened and GD1 was confirmed. Both children were found to have the same novel mutation. Evaluation of the sister revealed no hepatosplenomegaly by CT scan or cytopenia on labs. Her biochemical markers have been elevated but stable. Our case report shows the phenotypic diversity of GD1 even among affected siblings with same mutation. This case suggests that flux of substrate glycolipid may be an important determinant of phenotypic diversity in GD1. Our case report emphasizes the need for careful study of GBA1 activity and mutation in patients believed to have pseudo‐Gaucher cells in a variety of diseases.

Intestine/Colon/IBD cv 2 PEDIATRIC COLLAGENOUS ‐ANOTHER CAUSE OF WATERY IN TODDLERS Laurel Prestridge1, Rosemary Young1, Diane Kocovsky1, Jon Vanderhoof2 1Pediatric , Boys Town National Research Hospital, Boys Town, NE; 2Pediatric Gastroenterology, Children's Hospital of Boston, Boston, MA (CC), a cause of chronic diarrhea in adults is often associated with autoimmune disease. It is rarely reported at less than five years of age. The symptoms of CC in adults include chronic watery diarrhea, abdominal discomfort, weight loss, and fecal incontinence and it is often misdiagnosed as . The visual appearance of the colonic mucosa is normal and diagnosis requires endoscopic biopsy at multiple levels in the colon due to the patchy nature of the changes. We report 2 cases of CC in otherwise healthy toddlers presenting with watery diarrhea. A 2 ½ year old female developed diarrhea. She had a prior history of cow’s milk intolerance with symptom resolution utilizing a hypoallergenic amino acid formula. The child transitioned to a normal toddler diet at 13 months of age and did well until the age of 30 months at which time she began having frequent loose stools. Toddler diarrhea was suspect but she had no response to carbohydrate restriction. Based on her prior history a trial of dairy restriction resulted in worsening diarrhea. The second child was a male who presented at 15 months of age with watery diarrhea that initally responded to a high fat, low carbohydrate diet however the symptoms returned at age 4. Stool cultures and viral assays on multiple occasions in both children were normal. Neither patient’s family had a history of autoimmune disorders. Upper and lower endoscopies were performed. The intestinal mucosa was visually normal but multiple biopsies demonstrated CC with subepithelial collagen bands in both children. Treatment was initiated with oral budesonide (3mg/day). The female showed a rapid response with resolution of diarrhea within one week. An attempt to wean her from the medication after 6 months resulted in an immediate relapse. Collagenous colitis should be considered in the differential diagnosis of toddlers with watery diarrhea unresponsive to usual dietary management. cv 3 PRESENTATION AND OUTCOMES OF HISTOPLASMOSIS IN PEDIATRIC IBD PATIENTS TREATED WITH ANTI‐TUMOR FACTOR ALPHA THERAPY Jennifer Dotson1, Hayat Mousa1, Dennis Cunningham2, Jonathan Honegger2, Jaggi Preeti2, Wallace Crandall1. 1Gastroenterology, Nationwide Children's Hospital, Columbus, OH; 2Infectious Disease, Nationwide Children's Hospital, Columbus, OH Objectives: Tumor necrosis factor alpha (TNFα) antagonists are commonly used to treat inflammatory bowel disease (IBD). Unfortunately, these agents may predispose patients to serious infections, including endemic fungal infections such as histoplasmosis. Limited data exist on the presentation, appropriate treatment, and outcomes of histoplasmosis in patients receiving anti‐TNFα therapy. We sought to describe cases of histoplasmosis in the setting of pediatric patients with IBD who received anti‐TNFα therapy, and to review the available literature on presentation, treatment, outcomes, and continuation of TNFα antagonists. Methods: We surveyed local pediatric gastroenterology and infectious diseases physicians to identify IBD patients who developed histoplasmosis while on anti‐TNFα therapy in the past 5 years. Chart reviews were conducted and cases were reviewed with their primary gastroenterologist and infectious diseases specialists. The existing medical literature was reviewed. Results: Three patients were identified. They presented with symptoms of fever, sweats, malaise, weight loss, headaches, cough, dyspnea, and chest pain within 2‐12 months of initiating therapy. In each case, immunosuppressive medications were held, and antifungal therapy was given. Anti‐TNFα therapy was resumed in 1 patient together with prolonged antifungal prophylaxis. All patients recovered from the infection and none had recurrence of active disease. On literature review, few pediatric cases were identified and none discussed restarting anti‐TNFα therapy. Discussion: We described 3 cases of patients treated with anti‐TNFα therapy who developed histoplasmosis, including 1 patient who resumed treatment with anti‐TNFα therapy in addition to antifungal prophylaxis. If anti‐TNFα therapy is resumed, close monitoring for symptoms of recurrence and screening (urine histoplasma antigen levels) for activation of disease are strongly recommended. cv 4 DISSEMINATED HISTOPLASMA CAPSULATUM AND PNEUMOCYSTIS CARINII PNEUMONIA IN A CHILD WITH CROHN’S DISEASE RECEIVING INFLIXIMAB Sonia Michail, Ryan Simon, Wright State Boonshoft School of Medicine, Dayton, OH Tumor necrosis factor alpha (TNF‐alpha) plays a crucial role in the cellular inflammatory response and regulates the body’s ability to effectively contain a number of opportunistic infections. Anti‐ TNF‐alpha therapy has been increasingly used in children with inflammatory bowel disease. Several reports of adult patents with tuberculosis, histoplasma, and pneumocystis have been associated with infliximab therapy. Many of these infections can become disseminated and carry a high risk of mortality. We report an eight year‐old child with disseminated histoplasma capsulatum and pneumocystis carinii pneumonia who had received infliximab as monotherapy for managing his Crohn’s disease. This child was diagnosed at age 2. He developed an idiosyncratic response with severe bloody diarrhea requring hospitalization with 5‐ASA preparations. The use of 6‐mercaptopurine was associated with drug‐induced . He received infliximab for 15 months before he developed intermittent fevers, cough, and hepatosplenomegaly. CT scan of his lungs showed large hilar adenopathy and a reticulo‐nodular pattern of the lung parenchyma. Biopsies of the hilar lymph nodes showed pneumocystis and lymph node tissue cultures grew histoplasma capsulatum. He had elevated serum titers for histoplasma and positive urine histoplasma antigens. He was placed on trimethoprim‐sulfamethoxazole and itraconazole therapy with good response and resolution of radiographic changes in the lungs and mediastinum within 4 weeks of therapy. This report highlights the importance of monitoring pediatric patients for potential infectious complications related to therapy with anti‐ TNF‐alpha. It is important to consider rare causes of opportunistic infections as more children are placed on biologic therapies. Histoplasma infections are especially important in endemic areas such as the Midwest where this patient resides. cv 5 ACUTE IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE(IBD):IDIOPATHIC OR MEDICATION‐INDUCED? Aakash Goyal, Shailender Madani, Namir Al‐Ansari, Suhasini Macha, Mohammad El‐Baba Pediatric Gastroenterology, Children's Hospital of Michigan, Detroit, MI BACKGROUND: Patients with IBD are at increased risk for (AP). The association of AP and IBD is described in adults and causes are biliary lithiasis, medications, duodenal Crohn’s disease (CD) or idiopathic. AP in children with IBD is not well studied. AIM: We sought to define incidence, causes and clinical outcomes of AP in pediatric IBD. METHODS: We reviewed charts of patients age 0‐17 years of IBD with AP at Children’s Hospital of Michigan from January 1998 to May 2009. AP was diagnosed on elevated serum and/or lipase >3 times upper limit of normal, and/or radiographic findings. RESULTS: We found 723 patients who were diagnosed with IBD: 519 of CD and 204 of (UC). There were 20 patients (11 males and 9 females) with AP and IBD: 16 CD and 4 UC. 5 had AP > 2weeks before IBD diagnosis and 8 had AP within 2 weeks of IBD diagnosis. 7 had AP after IBD diagnosis. 13 patients were not on medications and 7 were on medications for IBD. 18 patients had abdominal ultrasound (USG), 8 had CT and 3 had MRI. 8 patients had radiologic evidence of AP, with abnormal USG in 5, abnormal CT in 1, and abnormal MRI in 2. Symptoms were mild to moderate in 19 patients and one was asymptomatic. 19 patients had one episode of AP and one developed . In 4 , AP was attributed to medications (azathioprine 2, mesalamine 1 and metronidazole 1). AP resolved after medication was discontinued. AP recurred on rechallenge in 2 on azathioprine. In 16 cause was not identified. In 8 cases who had AP within 2 weeks of IBD diagnosis, AP resolved after treatment for IBD was started. CONCLUSIONS: AP was seen in 2.8% of patients with IBD. Out of total 423 cases of AP, IBD related AP contributed to 4.7%. AP can precede or can be initial manifestation of IBD. Symptoms are mild with benign course in majority. Imaging studies are normal in more than half. AP is related to IBD activity in majority and to less extent due to medications and resolves after IBD activity is controlled or offending drug is removed. cv 6 IS ACUTE PANCREATITIS ANOTHER EXTRA INTESTINAL MANIFESTATION OF INFLAMMATORY BOWEL DISEASE? Melawati Yuwono1, Thomas Rossi2, Daniel Lustig1 1Pediatric GI, Mary Bridge Children's Hospital, Tacoma, WA; 2Pediatric GI, Strong Memorial Hospital, Rochester, NY Introduction: Episodes of acute pancreatitis in inflammatory bowel disease (IBD) have been attributed to cholelithiasis or medications. We report four cases of acute pancreatitis in pediatric ulcerative colitis (UC) patients in the absence of anatomic abnormality of the or link to medications, namely 6‐mercaptopurine (6‐MP). Methods and results: The four patients with UC included in the study were identified to have acute pancreatitis. They were between 5 and 14 years of age (median age 10 years; two female and two male). Three presented with abdominal pain and intermittent bloody stool, while one patient presented with back pain 1.5 months after his total colectomy. The residual rectal stump exhibited active colitis and persistent pseudopolyps. None of the patients received steroids prior to the onset of symptoms and had never received 6‐MP. Abdominal ultrasound exams were normal in all patients. Two patients underwent endoscopy retrograde cholangio pancreatography (ERCP), which showed no anatomic abnormalities. The remaining two patients did have magnetic resonance cholangio pancreatography (MRCP) performed and were normal in both cases. Amylase and lipase values remained elevated for one week to two months. Pancreatitis resolved in all patients with supportive care and none developed any sequelae or relapses for up to three years of follow up. All patients continued to receive their mesalamines drugs except one patient who had previous colectomy. Conclusions: 1)Acute pancreatitis in UC is not always related to 6‐MP as previously described. 2)Acute pancreatitis should be considered as an extra‐intestinal manifestation of UC in the absence of other causes. 3)In patients with UC, the use of mesalamines was not associated with increased risk of acute pancreatitis. cv 7 POORLY DIFFERENTIATED INFILTRATING CARCINOMA OF THE COLON IN A 14‐YEAR‐OLD FEMALE Wednesday Marie A. Sevilla1, Amir Kagalwalla1,2, Armeet Ded2. 1Pediatrics, University of IL at Chicago College of Medicine, Chicago, IL; 2John H. Stroger Jr. Hospital of Cook County, Chicago, IL Background: Chronic abdominal pain is a common complaint in children and adolescents with myriad causes. We present a very unusual case of a 14 year old female with chronic abdominal pain who had colon cancer. Case Report: 14‐year‐old Polish American female presented with a 10‐week history of intermittent crampy right lower quadrant and epigastic abdominal pain associated with and non‐ bloody vomiting. Pain was provoked by heavy meals and spicy foods. She also had anorexia, 3.8 kg weight loss, fatigue, malaise and weakness. There was no history of diarrhea or . Family history was unremarkable for any chronic gastrointestinal disorders including malignancies. Physical examination was remarkable for mild tenderness of the right lower quadrant. She failed to improve with adequate trial of acid suppression therapy with a proton pump inhibitor. Preliminary investigations including CBC with differential, electrolytes and ESR were within normal limits. An upper GI with small bowel follow through demonstrated diffuse narrowing of terminal , with cobble stoning, mucosal thickening of the cecum consistent with ileo‐colonic crohn’s disease. Colonoscopy findings included a 5 mm sessile in the and a 2cm pedunculated polyp in the sigmoid colon which were removed by snare technique. In addition ulcerating lesion was seen in the cecum extending to the terminal ileum was biopsied and was consistent with diffuse poorly differentiated infiltrating carcinoma in the cecum confirmed with AE1/AE3 keratin immunostaining. The polyps did not demonstrate dysplastic changes. Patient subsequently underwent extended right hemicolectomy with lymph node resection followed by chemotherapy. Conclusion: is an extremely uncommon diagnosis in children and adolescents. This malignancy carries a poor prognosis and delay in diagnosis can further dim the prognosis for this condition. Increased awareness of colon cancer leading to early diagnosis is essential if the outcome is to improve. cv 8 CEREBRORETINAL MICROANGIOPATHY WITH CALCIFICATIONS AND , A RARE CAUSE OF SEVERE GASTROINTESTINAL BLEEDING IN A 14 YEAR OLD Anna K. Hunter3, Josh Friedman3, Pierre Russo1, Robert Schnepp3, Netan Chhudhry2, Matthew Ryan3 1Pathology, Children's Hospital of Philadelphia, Philadelphia, PA; 2Ophthalmology, Children's Hospital of Philadelphia, Philadelphia, PA; 3Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA The causes of gastrointestinal bleeding in children and adolescents are varied and the incidence of bleeding is not well established. Common pediatric causes of upper GI bleeding include peptic ulcers, , Mallory‐Weiss tears, foreign bodies, , Dieulafoy's lesions and IBD. Less common manifestations include vascular anomalies, duplication cysts, hemobilia and tumors. We report a case of a 14 year old male who came to us for a second opinion regarding a prior diagnosis of Crohn’s disease with chronic anemia requiring multiple transfusions. His initial presentation included bloody stools and hypoalbuminemia. Endoscopic and video capsule evaluation revealed multiple hemorrhagic lesions in the antrum that extended into the mid . Biopsies revealed dilated capillaries within the lamina propria, but no inflammation. Ophthalmologic examination revealed retinal proliferative telengiectasias. Further testing showed extensive calcifications and teleangiectasias with formation in the brain as well as arterio‐venous malformations and teleangiectasias in the chest, liver and abdominal vasculature. These findings along with a recent cognitive decline, led to a rare diagnosis of cerebrotretinal microangiopathy with calcifications and cysts, disorder described in 28 cases worldwide. This is the first case to be evaluated by video capsule endoscopy. The extensive lesions precluded surgical resection. Therefore, patient was treated with argon plasma coagulation of the stomach lesions and prednisone therapy, resulting in a reduction in the transfusion dependence. Extensive vascular malformations of the are a difficult therapeutic challenge. When possible, primary resection and coagulative therapy remain methods of choice in acute bleeding. Pharmacotherapy for recurrent bleeding is limited by lack of evidence‐based literature. cv 9 DUODENAL HEMATOMA AFTER ENDOSCOPY WITH BIOPSY IN A CHILD WITH NOONAN SYNDROME Jonathan R. Ramprasad1, Mutaz Sultan1, Carla Laos2, Kyle Jensen1. 1Medical College of Wisconsin, Milwaukee, WI; 2Baylor College of Medicine, Houston, TX Background: Duodenal hematoma is a known, but rare complication after upper endoscopy (EGD) with biopsy. In children the complication is associated with growth failure, coagulopathy or anticoagulant therapy. Noonan syndrome (NS) is an autosomal dominant condition with a specific phenotype including: failure to thrive (FTT), short stature, hypertelorism, webbed neck, pulmonic valve stenosis, and mild mental retardation. Coagulation defects have been reported in patients with NS. Duodenal hematoma (DH) in an adult with NS has been reported once, but no similar reports exist in the pediatric literature. Case Report: RC, a 15 month old male with NS, was followed by GI for FTT. He had normal imaging and labs prior to EGD (CBC, chemistry profile, thyroid, LFT’s, giardia screen) and no history of easy bruising or bleeding. EGD with pancreatic stimulation, performed as part of his FTT evaluation, showed a hiatal with no excessive bleeding from biopsy sites. Histology and pancreatic stimulation were normal. 24 hours later, RC developed bilious emesis and tachycardia. Labs revealed a hemoglobin of 8.5 g/dL (from 10.5), PT 17.5, INR 1.77, fibrinogen 102, D‐Dimer 2.64 and lipase 7400. Abdominal x‐ray showed a non‐obstructive bowel gas pattern but a nasogastric tube was placed due to concern for obstruction. Abdominal CT revealed a 47 x 36 x 52 mm mass lesion near the porta hepatis, following the course of the and consistent with DH. Hemoglobin fell to 6.5 g/dL; he responded to cryoprecipitate and packed red blood cell transfusions. RC was managed conservatively with NG decompression and TPN. His pancreatitis resolved and the DH required no intervention. He required no additional transfusions and resumed enteral feedings on the tenth day post‐endoscopy. Conclusion: This is the first reported pediatric case of NS and DH. NS is associated with coagulopathy and presents an increased risk of complications. Prior knowledge of this association alerts the endoscopist, pediatrician and hematologist to the risk of bleeding during procedures. cv 10 ACUTE BILATERAL HYDRONEPHROSIS WITH RENAL FAILURE AND POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES) FOLLOWING INFLIXIMAB INFUSION IN CROHN'S DISEASE (CD) Narmer Galeano1, Teresa Rivera‐Penera1, Michael Delisi6, Jose R. Salcedo4, Orestes Sanchez2, Edward Milman2, Robin Frank‐Gerzberg2, Poorvi Patel5, Barbara Cocovinis3. 1Pediatric Gastroenterology and Nutrition, St. Joseph's Children's Hospital, Paterson, NJ; 2Division of Radiology, St. Joseph's Hospital and Medical Center, Paterson, NJ; 3Pediatric Intensive Care Unit, St. Joseph's Children's Hospital, Paterson, NJ; 4Pediatric Nephrology, St. Joseph's Children's Hospital, Paterson, NJ; 5Pediatric Neurology, St. Joseph's Children's Hospital, Paterson, NJ; 6Family Health Center, St. Joseph's Hospital and Medical Center, Paterson, NJ Hydronephrosis is a urological complication of CD most commonly occurring unilaterally. Neurological complications of CD are relatively uncommon and PRES has been reported only once in a child after Infliximab injection (JPGN 2008;48:102‐105). We report a case of an 8 year old girl with Crohn's disease. She presented with fever of unknown source followed by diarrhea, vomiting, abdominal discomfort and weight loss. She was anemic and hypoalbuminemic, without edema, and had mild rash in distal lower extremities. Endoscopy showed esophageal erosions and severe segmental colonic ulcerations with microgranulomas. Initial abdominal CT showed segmental thickening of distal ileum, ascending colon, hepatic flexure and proximal descending colon with no evidence of hydronephrosis. She received Infliximab 5 mg/kg along with IV steroids. Three days later, she became progressively oliguric (with a creatinine level up to 4 gm/dl) hypertensive, lethargic and had seizures. A head MRI showed increased T2 signaling along occipital , parietal and frontal lobes compatible with PRES. Abdominal US revealed bilateral hydronephrosis and MRI showed bilateral distal ureteral obstruction and thickening of the bladder wall. She underwent bilateral nephrostomies after which she had rapid improvement of the renal function and neurological status. Repeat head MRI showed significant improvement and nephrostomy tubes were removed after 10 days. She continued to receive steroid and was started on sulfasalazine and 6 mercaptopurine with favorable results. cv 11 RAYNAUD’S PHENOMENON HERALDS DIAGNOSIS OF CELIAC DISEASE Lisa Daigle1, Scott Oberhoff2, Jane El‐Dahr2, Ilana Fortgang1. 1Division of GI, Pediatrics, Tulane University, New Orleans, LA; 2Division of Allergy and Immunology, Pediatrics, Tulane University, New Orleans, LA Celiac disease (CD) is the arising from gluten intolerance. It promotes an inflammatory response resulting in small bowel mucosal damage with intestinal , weight loss and growth failure. The pathogenesis of CD evolves from the mechanisms by which gluten peptides cross the epithelium into the lamina propria where they are deamidated by tissue transglutaminase (tTG) and presented to CD4+ cells, hence activating a robust Th1 response. The end result is upregulation of a slew of proinflammatory cytokines that function also to increase systemic vasoactivity. Extraintestinal manifestations of CD include the unique rash, dermatitis herpetiformis, which can occur in the absence of gastrointestinal symptoms, and sequellae of untreated disease including neurologic deficits, infertility, and dental enamel defects. CD is estimated to afflict 1 in 300 to 1 in 80 children in the US. Patients with certain autoimmune diseases, among them type 1 , arthritis and common variable immunodeficiency, are at higher risk for CD. There is a recognized genetic component to these affiliations. Association of CD with other syndromes is more tenuous. Herein we present the case of an 8‐ year‐old girl whose first symptom of CD was Raynaud’s phenomenon. Because this vasospastic disorder is associated with a variety of autoimmune diseases, initial workup led to revelation of multiple markers of inflammation: ANA of 1:10,240, elevated CRP of 2.6 mg/dL and ESR of 60, as well as HCT of 30, and AST of 71 and ALT 73. The last prompted evaluation of celiac serologies which revealed an elevated α‐tTG of 267. Endoscopic findings and histology were classic for CD: dull and friable duodenal mucosa; intraepithelial lymphocytes and blunted villi. A gluten‐free diet was implemented, and the child has experienced ongoing resolution of her symptoms. This case highlights an unusual presentation of CD and promotes consideration of the pathophysiology and downstream effects of this systemic inflammatory disorder. cv 12 USE OF SIROLIMUS TO TREAT REFRACTORY INFLAMMATORY BOWEL DISEASE Babu Vadamalayan1,2, Keith Lindley2,1.1Paediatric Gastroenterology, King's College Hospital, London, United Kingdom; 2Gastroenterology, Great Ormond Street Hospital, London, United Kingdom Aim: Sirlomius and Mycophenolate mofetil(MMF) have been used extensively as immunosuppressants after organ transplantation but this has not been used in children with Inflammatory Bowel Disease. We report a child with resistant inflammatory bowel disease (IBD) who responded well to this combination treatment. An 8 year old boy was diagnosed to have indeterminate colitis at the age of four following extensive investigations after having chronic diarrhoea for 2 years. He was initially treated with mesalazine, sulfasalazine, azathioprine and predinsolone. He was then started on infliximab infusions in view of recurrent symptoms (ESR 80mm/hr, Platelets 683 x109/L, Hb 11.4g/dl and biopsy showed severe chronic active pan colitis with mild gastritis but without granuloma). His symptoms initially improved but diarrhoea worsened again needing further treatment. A year later, in view of recurrent symptoms he was started (weight 22kg) on adalimumab at 20mg (subcutaneous injection) every 2 weeks and also started on sirolimus 2 mg (orally) once a day and MMF 250mg (orally) twice a day at the same time. Sirolimus level was low (3.6 ng/ml) initially and the dose was increased to 3 mg subsequently (aimed to keep between 10‐12 ng/ml). His symptoms improved and he became asymptomatic on this combination treatment. Adalimumab was stopped a year later and he is currently on sirolimus, MMF and mesalazine without any symptoms. He is gaining weight and inflammatory markers were all normal (Hb 12.2 g/dl, WCC 6.9 x109/L, Plats 343 x109/L, ESR 9 mm/hr, albumin 47 g/l ). Repeat endoscopy 15 months after he was started on sirolimus showed very mild chronic inflammatory changes in colon. Conclusion: This is the first case report of Sirolimus induced remission in Paediatric Inflammatory Bowel Disease (IBD).

Nutrition/Nutrition Support cv 13 TYPE I REFRACTORY IN CHILDHOOD Babu Vadamalayan1,2, Keith Lindley2,1. 1Paediatric Gastroenterology, King's College Hospital, London, United Kingdom; 2Gastroenterology, Great Ormond Street Hospital for Children, London, United Kingdom Aim: Refractory coeliac disease (RCD) is rare. RCD is defined as persistence of small intestinal biopsy changes despite strict adherence to gluten free diet (GFD) for at least 6 months. RCD can be divided into type I (with out aberrant T cells), which responds to nutritional therapy or immunosuppressive therapy and type II (with aberrant T cells) which carries a poor prognosis, which is also difficult to treat. Methods: We report a child with type I refractory celiac disease, which was resistant to conventional treatment and needed immunosuppressive therapy to control the disease. Results: A 4 year old girl was diagnosed to have celiac disease following positive anti tissue transglutaminase antibody and crypt hyperplasic sub‐total villous atrophy and increased intraepithelial lymphocytes on intestinal biopsy. Her symptoms improved (diarrhoea, lethargy, poor weight gain, severe dry skin and irritability) and had negative tTG on gluten free diet. Approximately 3 months later she started to have diarrhoea again. She was tried on pauciantigenic diet with little effect and eventually elemental feeds with a degree of clinical response. She had normal total IgE, RAST, ESR, CRP, auto antibody screening, immunoglobulin levels and colonoscopy. Her repeat anti tTG was negative but OGD showed villous blunting, increased IEL and crypt hyperplasia. Immunohistochemisrty showed mixture of CD4, CD8 lymphocytes in lamina propria but exclusively increased infiltration of CD8 intra epithelial lymphocytes (45 lymphocytes per 100 enterocytes). Subsequently she was started on anti inflammatory and immunosuppressant medications including azathioprine with good response. Currently, She is 7 years old and well on the above therapy. Conclusion Loss of response to GFD needs to be investigated and trial of Pauciantigenic diet, elemental feeds and immunosuppressive therapy should be considered. Further studies are needed to assess the prevalence of RCD among children.

cv 14 CHYLOUS ASCITES: A RARE COMPLICATION OF LAPAROSCOPIC FUNDOPLICATION K. T. Park1, Boma Adikibi2, Karl Sylvester1, Gordon MacKinlay2, Peter Gillett2, John Kerner1 1Lucile Packard Children's Hospital, Stanford University Medical Center, Palo Alto, CA; 2Pediatric Surgery, Royal Hospital for Sick Children, Edinburgh, United Kingdom Case 1: A 6 year old male with DiGeorge Syndrome who underwent laparoscopic Nissen fundoplication developed significant ascites several weeks post‐operatively. Paracentesis with peritoneal drain placement confirmed chylous ascites with albumin and triglyceride concentrations of 2.5 g/dL and 1,295 mg/dL, respectively. Three liters of chyle drained in the initial 24 hours. Due to persistence of chylous drainage despite both a low and a non‐fat diet, NPO/TPN therapy was initiated with resultant decrease of drain output. A non‐fat diet was reintroduced 4 weeks after NPO/TPN therapy without reaccumulation of chyle. Oral intake was gradually liberalized and TPN was weaned off over the next two weeks. Case 2: A 2 year old with Cornelia de Lange syndrome who underwent a laparoscopic Nissen fundoplication with gastrostomy tube placement developed ascites on post‐operative day 1. Paracentesis with peritoneal drain placement on post‐op day 6 confirmed chylous ascites with a triglyceride concentration of 221 mg/dL. NPO/TPN therapy was started on post‐op day 7. Due to ongoing drainage output despite dietary restriction of fat, octreotide drip was started (initially at 0.5 mcg/kg/hr, gradually titrated up to 10 mcg/kg/hr) beginning on post‐op day 11. The peritoneal drain was removed by post‐op day 19 with introduction of low‐fat diet by day 21. Octreotide was weaned off by post‐op day 26. Normal diet was tolerated 6 weeks post‐operatively. Conclusion: Chylous ascites is a rare complication of abdominal surgery. Only one pediatric case of chylous ascites after laparoscopic Nissen fundoplication has been previously reported prior to our two reported cases. Choices for non‐operative management of chylous ascites include: dietary fat restriction, TPN/NPO therapy, and octreotide infusion. Our two cases show two different approaches to effective treatment of chylous ascites when restriction of dietary fat fails to decrease chylous output. cv 15 HORMONAL DYSREGULATION IN DIENCEPHALIC SYNDROME: A CASE WITH NEW DATA Daniel Mallon1,2, Dennis Christie1,2. 1Pediatrics, University of Washington School of Medicine, Seattle, WA; 2Seattle Children's Hospital, Seattle, WA Diencephalic syndrome (DS) is defined by a constellation of clinical signs, including emaciation, preserved linear growth, alert appearance, vomiting, hyperkinesis and nystagmus in association with brain tumors originating in the hypothalamus. The pathogenesis of the emaciation includes increased energy expenditure, and certain endocrinologic pathways have been posited, with special attention given to growth hormone (GH) dysregulation. One proposed mediator of growth hormone dysregulation is ghrelin, the measurement of which has not yet been reported in a case of DS. Our patient is an 18 month‐old girl who presented with plateaued weight gain and preserved linear growth despite nutritional supplementation, intermittent vomiting, nystagmus and a happy affect. She was the product of a normal pregnancy, and from birth through 6 months, her weight and height were consistently near the 50th percentile. Then, her weight plateaued such that at 18 months, despite being near the 50th percentile for height, she was well below the 3rd percentile for her age and indeed at the 50th percentile for 7 month old girls. At the time of presentation, an MRI of her brain showed a 4x3x3 cm left hypothalamic/thalamic mass, which biopsy revealed to be a pilomyxoid astrocytoma. Prior to initiating therapy, several hormone levels were measured: ‐like growth factor 157 ng/ml (49‐290), insulin‐like growth factor binding protein‐1 1.3ng/ml (20‐105), growth hormone 1.3 ng/ml (0‐5), ghrelin 874 pg/ml (520‐700). To our knowledge, this is the first report of elevated ghrelin levels in a patient with diencephalic syndrome. Ghrelin is normally elevated in the fasting state, elevation of ghrelin has been reported in the starved state of anorexia nervosa, and it is a normal secretagogue of GH. These data further the hypothesis that the disease state of DS may alter ghrelin release, and ghrelin may play a role in GH dysregulation.

cv 16 TRICHOTHIODYSTROPHY: A RARE CAUSE OF GROWTH IMPAIRMENT Michael A. Russo. 1Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX; 2Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Medical Center at Legacy, Plano, TX Trichothiodystrophy (TTD) is a rare, autosomal recessive disease, in which patients present with a wide spectrum of clinical involvement. The most definitive clinical criteria is the cutaneous abnormality present in a patient's hair. The hair shaft is brittle and sulfur deficient that displays a diagnostic alternating banding pattern under polarising microscopy. Critical from a gastroenterology (GI) perspective is the reported feature of growth retardation present in nearly 75% of this patient population. Multiple liver hemangioendotheliomas have also been reported in TTD.

A former 35 week preterm toddler born to non‐consanguinous parents presented with a chief concern of poor weight gain at 16 months of age. He had a history of multiple food intolerances with the reported consequence of diarrhea. Failure to thrive with the clinical feature of weight & height less than the 3rd percentile was present. Coarse, thin hair and ichthyosis were notably consistent with TTD. An extensive workup was completed excluding immune deficiency, pancreatic insufficiency, congenital short bowel, , disaccharide deficiency, and celiac disease. Esophagogastroduodenoscopy and ileocolonoscopy were performed as part of the evaluation and histologic villous architectural, allergic, and inflammatory abnormalities were not detected histologically. Specific dietary restrictions (based on food challenge response) with elemental formula supplementation led to improved growth parameters and resolution of diarrhea. Given the variety of phenotypic features including growth abnormalities, patients with TTD are likely to present to pediatric gastroenterologists. Albeit a rare entity, familiarity with this diagnosis is critical to optimal care for these patients. Additionally, while ectodermal abnormalities may be obvious, this case illustrates that endoscopy may be safely performed. cv 17 RETROGRADE MIGRATION OF A GASTRO‐JEJUNAL TUBE TO THE OROPHARYNX Shabina Walji‐Virani1,2, Michael A. Russo1,2. 1Gastroenterology, Hepatology and Nutrition, Childrens Medical Center, Dallas, Dallas, TX; 2Pediatric Gastroenterology, University of Texas Southwestern, Dallas, TX Gastrostomy tubes (GT) are the preferred route to provide enteral nutritional support to children with impaired oral intake. Benefits of enteral feedings clearly out weigh total parenteral nutrition. Transpyloric feedings via a gastro‐jejunal tube (GJT) are indicated when children are intolerant to GT feeds due to high pulmonary aspiration risk, severe gastroesophageal reflux (GERD), , oropharyngeal dysphagia, gastric outlet obstruction or pancreatitis. Complications with postpyloric enteral feedings include blockage of the lumen, leakage at the GT site, duodenogastric reflux, , jejunal and displacement or migration of the tube’s jejunal limb. The following case illustrates an unusual migration of the GJT. A 16 year old male with significant neurological impairments and dysfunctional swallowing presented with severe GERD, possible aspiration and weight loss. He had been receiving continuous enteral feeds through his GT. Given his high risk for recurrent aspiration pneumonia, the decision was made to replace his GT with a fluoroscopically placed GJT. This GJT made a remarkable positive impact in his overall health with weight gain and resolution of his GERD symptoms including antecedent pulmonary issues. Few weeks later, he awoke coughing with notable intermittent cyanotic episodes. The jejunal limb of his GJT was seen in his oropharynx. Consequently, the GJT was immediately removed. Migration of the GJT is a known potential complication of transpyloric feedings. Traditionally, this occurs with either tube migration distally or in a retrograde manner proximal to the ligament of Treitz. Retrograde migration past the esophageal sphincters into the oropharynx is an exceedingly unusual occurrence. A potential esophageal motility issue with incompetence of the lower esophageal sphincter is implied. Alternatively, cough / retching with associated valsalva may have been a contributor. To our knowledge, this is the first report of such significant proximal GJT migration.

Pancreas/Cystic Fibrosis cv 18 PANCREATITIS FOLLOWING DUODENAL OBSTRUCTION Anupama Chawla1, Thomas K. Lee2, Albert O. Kwon2. 1Pediatrics, Stony Brook University, Stony Brook, NY; 2Surgery, Stony Brook University, Stony Brook, NY Introduction: Etiology of pancreatitis in a handicapped child can be difficult to determine.We describe 2 cases of duodenal obstruction who presented with pancreatitis.In each case, resolution of the duodenal obstruction resulted in normalization of pancreatic . Case 1:A 14 mth MRCP female with a G‐ tube presented with 1 day of abdominal pain and non‐bilious emesis. She had a soft abdomen with a foley catheter serving as a G‐tube. Pancreatic enzymes were elevated. Abdominal imaging showed migration of the foley balloon to the proximal duodenum. The G‐tube was pulled back to the appropriate position. By day 3, pancreatic enzymes normalized with tolerance of G‐tube feeds. Case 2: A 10 year‐old MRCP male presented with abdominal distension and pain for 2 days with inability to tolerate G‐tube feeds. Four months prior he had a cholecystectomy for . Pancreatic enzymes were elevated. Abdominal CT scan demonstrated superior mesenteric artery (SMA) syndrome. After failing attempts of gastric or duodenal feeds he underwent Roux‐en‐Y duodeno‐jejunostomy. Postop he tolerated G‐tube feeds with near normalization of pancreatic enzymes. Discussion: In both cases, pancreatitis occurred in the presence of duodenal obstruction.With resolution of obstruction,rapid normalization of pancreatic enzymes occurred with tolerance of G‐tube feeds. Acute pancreatitis and cholangitis have been reported in children with the migration of gastrostomy tubes. However no cases of pancreatitis in patients with SMA syndrome have been reported.The etiology is presumably similar in both cases with duodenal obstruction leading to pancreatic inflammation. This series calls for a heightened awareness of duodenal obstruction as a potential cause for pancreatic inflammation. Pacreatic enzymes with and without duodenal obstruction

With duodenal obstruction Without duodenal obstruction Case 1 Amylase (units/L) 206 (28‐100) 66 Case 1 Lipase (units/L) 999 (7‐59) 58 Case 2 Amylase(units/L) 131 73 Case 2 Lipase (units/L) 346 116

cv 19 THE CURIOUS CASE OF CHRONIC DIARRHEA—A RARE PRESENTATION OF PANCREATIC VIPOMA IN AN 11 YEAR‐OLD MALE Jennifer Jimenez1, Nneka Nzegwu1, Catherine Chao2, Lynn Duffy2, Peter Lee2, Ian Leibowitz2, Otto Louis‐ Jacques2, Benjamin Enav2. 1Pediatrics, Inova Fairfax Hospital for Children, Falls Church, VA; 2Pediatric Gastroenterology, Inova Fairfax Hospital for Children, Falls Church, VA An 11 year‐old male presented to the ED with chronic diarrhea, dehydration, syncope and a 20 lb weight loss. His diarrhea began 11 months prior to presentation after visiting Cancun. Numerous stool studies were done to rule out infectious etiology. Upper endoscopy 3 months after the diarrhea started demonstrated a disaccharidase deficiency with normal histology. Dietary restriction provided no relief in his symptoms. At the time of admission, he was having 10 watery, non‐bloody stools per day. Basic metabolic panel showed a CO2 of 11meq/L and creatinine of 1.6 mg/dL. ESR, CBC, CRP and CMP were normal. Stool volume while NPO was up to 20 L/day. Fecal electrolyte studies were consistent with a secretory diarrhea. Flushing episodes prior to defecation were observed. Therapy with octreotide drip led to decreased stool output. Blood levels of vasoactive intestinal peptide (VIP) were elevated at 400 pg/ml (normal 20‐42 pg/ml). An abdominal CAT scan and octreotide scan were normal. An MRI of the abdomen revealed innumerable hepatic nodules and a hypodensity in the tail of the . The pancreas was further evaluated by endoscopic ultrasound demonstrating a mass in the tail. The patient underwent a liver biopsy and distal with histopathology confirming the diagnosis of a malignant pancreatic VIPoma. Conclusion: VIPoma is a rare neuroendocrine tumor characterized by prolonged, watery diarrhea with an incidence of 1 in 10 million per year. Most cases are metastatic at presentation due to difficulty in establishing the diagnosis and the indolence of the disease. Diagnosis and management of a patient with a VIPoma requires a multidisciplinary approach, multiple imaging modalities and diligence with regards to fluid resuscitation, electrolyte replacement, and maintenance of intravascular volume. cv 20 ISOLATED AMYLASE DEFICIENCY AS A CAUSE OF FAILURE TO THRIVE Shamila B. Zawahir, Anjali Malkani, Samra Blanchard, Steven Czinn. Pediatrics, Division of Pediatric Gastroenterology and Nutrition, University of Maryland, Baltimore, MD Background: Isolated (pancreatic) amylase deficiency is a rarely reported entity resulting in starch malabsorption and symptoms of abdominal pain, flatulence, diarrhea and poor weight gain. Adult levels of pancreatic enzymes are normally achieved by 18 months in duodenal fluid. Failure to detect pancreatic amylase may be the result of physiological absence, delay in maturation, or deficiency. Case Report: An 18‐month old Ashkenazi Jewish female presented with chronic diarrhea, failure to thrive, abdominal distension and flatulence since 6 months of age. In addition, she had poor hair growth, multiple upper respiratory tract infections with frequent exposure to antibiotics and excessive napping. Between 14 and 18 months of age she had fallen from the 10 ‐ 25th percentile for weight for height to well below the 5th percentile. At 18 months of age, exam revealed a small girl with thin short hair, protuberant abdomen and little subcutaneous fat. Stool reducing substances were positive and stool pancreatic elastase was normal; she had a normal hemoglobin level and 25‐OH‐Vitamin D level with no evidence of renal tubular acidosis or cyclic neutropenia. EGD and flexible sigmoidoscopy showed normal histology with normal disaccharidases. Pancreatic stimulation test using secretin revealed alkaline duodenal fluid with isolated deficiency of amylase. She was started on pancreatic enzyme supplementation. After 3 months of therapy her height has increased to the 10 ‐ 25th percentile and she has been gaining 4.5 g/day (normal: 4 ‐ 10), double her previous growth rate. Her diarrhea has resolved and she has had fewer acute infectious issues, improved hair growth and sleeping pattern. Conclusions: Isolated amylase deficiency may be a cause of failure to thrive and a normal stool pancreatic elastase level does not rule this out. Hence, pancreatic stimulation tests should be considered during evaluation for failure to thrive. Pancreatic enzyme supplementation is associated with improvement symptoms associated with this condition. cv 21 ISOLATED TRYPSIN AND CHYMOTRYPSIN DEFICIENCY IN A 2 YEAR OLD MALE Ari Dorros, Carol Greene, Anca Safta. University of Maryland Medical Center, Baltimore, MD Background: Isolated trypsin and chymotrypsin deficiency is a very rare cause of poor growth and malabsorption. Pancreatic insufficiency is the inability of the exocrine pancreas to produce and transport enough digestive enzymes for proper and absorption. This can be the result of progressive pancreatic damage that may be caused by cystic fibrosis (CF), Shwachman‐Diamond Syndrome, acute or chronic pancreatitis, and type 1 or autoimmune diabetes. Pancreatic insufficiency symptoms include malnutrition, malabsorption, , bulky stools, abdominal pain, flatulence, vitamin deficiencies, and failure to thrive. A useful indirect test for severe pancreatic insufficiency is Fecal Pancreatic elastase‐1 (FE1), a proteolytic pancreatic enzyme, which binds to bile salts, and does not degenerate in the intestine. However, a secretin stimulation test is required for mild pancreatic insufficiency, since is has a higher sensitivity. Patient: A two year old, full term male, with poor weight gain, eczema, and bloody diarrhea on presentation. Initially he was diagnosed with cow’s milk and soy protein allergy. Clincal Course: Elemental formula was commenced which resolved the bloody diarrhea. However, he still continued to have rashes, poor growth, steatorrhea, and brittle hair. He also developed iron deficiency anemia and low vitamin D levels. He had abnormal qualitative fecal fat on two consecutive tests. FE1 was normal, and he underwent an endoscopy with secretin stimulation. Biopsies did not show any abnormal pathology; however, the pancreatic fluid showed isolated trypsin and chymotrypsin deficiency with an alkaline pH. Sweat chloride collection was normal. CF, Shwachman‐Diamond, and Pearson syndrome were ruled out. His signs and symptoms improved on iron, vitamins, and pancreatic enzyme supplementation. Conclusion: Isolated trypsin and chymotrypsin deficiency is an uncommon cause of poor growth and malabsorption, which can be successfully diagnosed with a secretin stimulation test. Successful treatment can be accomplished with pancreatic enzyme supplementation, iron, and vitamins. cv 22 ACUTE PANCREATITIS AFTER PROPOFOL ADMINISTRATION IN A CHILD WITH WAGR SYNDROME Kristen M. Danley1, Wendy A. Henderson2, Tommy Ibrahim2, Colleen M. Hadigan3, Joan C. Han1 1Unit on Growth and Obesity, NICHD, Bethesda, MD; 2Biobehavioral Unit, NINR, Bethesda, MD; 3Clinical Research Section, NIAID, Bethesda, MD Propofol is a widely used anesthetic that is delivered in a lipid emulsion and has been associated with pancreatitis in case reports. We now describe a 12‐year‐old female with WAGR (Wilms tumor, aniridia, genitourinary anomalies, mental retardation) syndrome, a disorder caused by chromosome 11p13 deletion, who was taking no medications and whose only active medical problems were obesity (BMI 30.2 kg/m2) and hypertriglyceridemia (823 mg/dL). Three hours after receiving midazolam (2mg) and propofol (2.5g) for sedated imaging in a research phenotyping study, the patient developed vomiting accompanied by abdominal pain. Amylase, lipase, and triglycerides were markedly elevated at 12 hours (Table). Active infections with hepatitis A, CMV, and EBV were ruled out. Abdominal ultrasound showed fatty liver, hypoechoic pancreas consistent with pancreatitis, no cyst or fluid collection, normal gallbladder, and no biliary dilatation. The patient was placed on NPO status and treated with IV fluids and fentanyl PCA. Clear liquid diet was initiated on day four; IV fluids were discontinued and solid diet resumed on day six. We hypothesize that propofol and/or its lipid carrier may have triggered acute pancreatitis in this patient who also had prior risk factors for pancreatitis, including hypertriglyceridemia and an underlying genetic disorder that involves deletion of PAX6, a transcription factor important in pancreas development and function.

Direct Amylase Lipase ALT AST Total bilirubin Time post Triglycerides bilirubin (U/L; (U/L; (U/L; (U/L; (mg/dL; sedation (mg/dL; nl<150) (mg/dL; nl<105) nl<105) nl<30) nl<38) nl<1.0) nl<0.2) 12 hours 731 4372 566 N/A N/A N/A N/A 1 day 1284 6903 489 52 23 0.6 <0.1 2 days 717 2632 300 29 8 0.6 0.1 4 days 205 695 175 18 21 1.0 0.4 6 days 172 790 N/A 38 23 0.7 0.3 7 days 181 996 N/A 42 31 0.3 0.1

cv 23 A CASE OF WEIGHT LOSS AND OBSTRUCTIVE JAUNDICE: ARE RADIOIMAGING AND STEROID RESPONSIVENESS ADEQUATE IN DIAGNOSING AUTOIMMUNE PANCREATITIS IN A CHILD? Ing Shian Soon1, Dana Boctor1, Marli Robertson1, Jonathan Love2, Christian Turbide2 1Pediatrics, University of Calgary, Calgary, AB, Canada; 2Internal Medicine, University of Calgary, Calgary, AB, Canada Autoimmune pancreatitis (AIP) is a new disease entity found in the older population with age of onset in the sixth decade. There have only been case reports in children, all diagnosed by tissue pathology. As well, pancreatic tumors are very uncommon in children. Herein, we present a 9‐year‐old boy with a two week history of pruritus, abdominal pain, acholic stools, choluria and weight loss. He was icteric with no hepatosplenomegaly nor abdominal mass. His initial lab investigations revealed with mild elevation in serum transaminases. Serum lipase and inflammatory markers were normal. IgG subclasses including IgG4, ANA, rheumatoid factor, anti‐smooth muscle screen and anti‐liver kidney microsomal antibody were negative. MRCP and abdominal CT showed an uncinate mass, a heterogeneous pancreas and dilated common . Fine‐needle aspirate did not reveal any evidence of malignancy. Despite biliary stent placement, the bilirubin continued to rise. Given the lack of other neoplastic features, and the potential morbidity in obtaining tissue specimen, a trial of prednisone for possible AIP was started at 40mg once daily for 4 weeks. It was then weaned at a rate of 5mg a week. The bilirubin started to decrease after two days of prednisone, and normalized by six weeks. By seven weeks, repeat MRI showed a dramatic improvement with normalization of the pancreas and biliary tree. The radiologic appearance, lack of evidence for and dramatic responsiveness to steroid suggest the diagnosis of AIP despite the lack of immune markers and in the absence of available pathologic specimen. Six months after prednisone was discontinued, a follow up MRI showed a normal appearing pancreas, and his bilirubin and transaminases remain normal. In the absence of features suggestive of neoplasm or infection, without a tissue diagnosis of AIP, a trial of corticosteroid in a pediatric patient may be reasonable to avoid an invasive surgical procedure. cv 24 MATURATIONAL DELAY OF PANCREATIC ENZYME SECRETION IN A PATIENT WITH PDD‐NOS Beth Loveridge‐Lenza, Karoly Horvath. Gastroenterology, A.I. duPont Hospital for Children, Wilmington, DE A Caucasian male who was full‐term and exclusively breast‐fed until 6 months of age had good initial weight gain. After he started ingesting formula his weight declined from the 25th to the 7th percentile within 3 months. He also showed signs of developmental delay. His first gastroenterological evaluation was at 17 months of age for failure to thrive, developmental delay, and chronic loose stools. His weight was below the 5th percentile for age and his height was at the 25% percentile. He appeared malnourished, had speech delay but was happy and active. Laboratory studies revealed anemia. PMH was positive for eczema. There was no family history of pancreatic disease. He underwent an EGD with pancreatic stimulation and was found to have generalized pancreatic insufficiency and normal histologies. He was started on pancreatic enzyme replacement therapy with significant improvement in his stool consistency, weight, behavior and developmental milestones. His sweat test was negative. He underwent extensive genetic and metabolic evaluations and all these tests were negative. He had never had neutropenia or increased number of infections. His growth parameters were normal on enzyme supplementation. He had repeat EGDs with pancreatic stimulation. At the age of 4 yrs continued to have generalized pancreatic insufficiency. However, at age of 7 he had low normal pancreatic enzyme activities and the supplementation was stopped. Two subsequent endoscopies revealed normal levels of all pancreatic enzymes. His growth parameters are age appropriate. His developmental delay remained a problem. The initial developmental evaluation by using the Kent Infant Developmental scales at age 17 months showed that his overall functioning was at a 10 month old range. Later he was diagnosed with PDD‐NOS. In the few last years he has been on various psychiatric medications. This case represents a non‐syndromic maturational delay in pancreatic function associated with developmental delay and behavioral problems