Severe Chronic Diarrhea Research Articles

7537 Composite Pheochromocytoma-Ganglioneuroma Secreting Vasoactive Intestinal Peptide: A Case Report

Abstract Disclosure: B. Brochu: None. Y. Collin: None. R. Temmar: None. F. Bernier: None. K. Dandurand: None. M. St-Jean: None. M. Massicotte: None. Background: Composite pheochromocytoma-ganglioneuroma is a rare tumor combining features of both pheochromocytoma/paraganglioma (PPGL) and neurogenic tumors. Cosecretion of vasoactive intestinal peptide (VIP) is even less common and highlights the diverse secretory potential of these tumors. Clinical Case: An 80-year-old woman presented with severe chronic diarrhea that had been progressively worsening over the past 10 years. The diarrhea was associated with chronic hyponatremia between 128 and 132 mmol/L. She also had mild hypertension, with a mean blood pressure of 145/90 mm Hg. An abdominal CT scan revealed a right adrenal mass of 68 mm x 44 mm x 50 mm with a density of 19 HU without contrast. A 24-hour urinary collection demonstrated normetanephrines (NM) levels at 3.5 times the upper limit of normal. A 68Ga-DOTATATE PET/CT demonstrated significant uptake only in the adrenal mass. Because of the ongoing severe diarrhea, that is unusual in the context of NM secreting PPGL, serum VIP level was measured and came back at nearly three times the upper limit of normal. A provisional diagnosis of pheochromocytoma with VIP and catecholamines cosecretion was made and surgical resection by laparotomy was performed without complication. Pathology demonstrated a composite tumor combining a pheochromocytoma and a ganglioneuroma, with a Pheochromocytoma of the Adrenal gland Scaled Score (PASS) score of 3. Tumor immunohistochemical staining was positive for VIP in both pheochromocytoma and ganglioneuroma cells. After surgery, diarrhea and hyponatremia resolved and blood pressure normalized. Conclusion: This is one of the very rare cases described in the current literature of a composite pheochromocytoma coproducing catecholamines and VIP. While the two tumors might have developed synchronously, the finding of VIP secretion in the pheochromocytoma and the ganglioneuroma suggest that both tumors might originate from the same cell. Presentation: 6/1/2024

Diagnosis and resolution of olmesartan-associated sprue-like enteropathy confirmed by capsule endoscopy: a case report and literature review.

Herein, we describe a case of olmesartan-associated sprue-like enteropathy, in which improvement in villous atrophy was confirmed using small bowel capsule endoscopy. The patient was a 69-year-old woman who had persistent watery diarrhea (20 bowel movements/day) for 1year and experienced a weight loss of 10kg in the same period. Abdominal computed tomography revealed no abnormalities, and blood test results revealed no inflammatory reactions. Upper endoscopy and colonoscopy revealed villous atrophy in the duodenum and terminal ileum. As the patient was administered olmesartan for a long time and capsule endoscopy showed villous atrophy throughout the small bowel, she was diagnosed with olmesartan-associated sprue-like disease. Following the discontinuation of the medication, symptoms of diarrhea soon improved, and repeat capsule endoscopy indicated improvement in small intestinal villous atrophy. Olmesartan-associated sprue-like enteropathy should be considered a differential diagnosis in patients with severe chronic watery diarrhea. Our report is the first in which capsule endoscopy was performed multiple times over a long period for follow-up observation of improvements in the small intestine. In addition, our literature review regarding capsule endoscopy for olmesartan-associated enteritis might aid clinicians in the early diagnosis of the condition and the assessment of treatment efficacy.

Disseminated Mycobacterium: A Rare Case of Chronic Severe Diarrhea in a Patient with HIV

Disseminated Mycobacterium: A Rare Case of Chronic Severe Diarrhea in a Patient with HIV

Association of microscopic colitis and enteropathy due to olmesartan.

We report the case of a patient with severe chronic diarrhea. He was admitted on multiple occasions for this reason, with the cause remaining undetected. After obtaining a detailed medical history and performing several studies, the patient was diagnosed with microscopic colitis and enteropathy due to Olmesartan. In the literature, both diseases appear concurrently only in a few cases. Here we highlight the importance of conducting a comprehensive medical history and maintaining high clinical suspicion to avoid delays in the diagnosis of these uncommon pathologies, as well as unnecessary tests and empirical treatments.

Ménétrier disease: a rare cause of severe chronic diarrhea difficult to diagnose with response to treatment with octreotide.

We present the case of a 71-year-old male with difficult to manage severe chronic diarrhea, who after multiple tests was finally diagnosed with Ménétrier's disease and had clinical improvement with treatment with intramuscular octreotide. A high degree of clinical suspicion is essential to diagnose this entity, exclude similar entities and the correlation of clinical, analytical, endoscopic, radiological and histological data.

Intractable diarrhea in infancy and molecular analysis: We are beyond the tip of the iceberg

BackgroundIntractable diarrhea (ID) could be defined as a syndrome of severe chronic diarrhea associated with malnutrition not easily resolved by conventional management. AimsTo provide an overview on etiology and management of ID patients in Italy in the last 12 years. MethodsThe members of Italian Society for Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) enrolled all ID patients seen between January 1, 2011 and December 31, 2022. Results69 children were enrolled (49 M, 20 F; median age at ID onset 9.5 days) from 7 tertiary care pediatric centers. Overall 62 patients had genetic diseases; 3 had infantile Inflammatory Bowel Disease and 1 autoimmune enteropathy in absence of genetic mutations; 2 undefined ID. Defects of intestinal immune-related homeostasis caused ID in 29 patients (42 %). ConclusionID is a rare but challenging problem, although the potential for diagnosis has improved over time. In particular, molecular analysis allowed to identity genetic defects in 90 % of patients and to detect new genetic mutations responsible for ID. Due to both the challenging diagnosis and the treatment for many of these diseases, the close relationship between immune system and digestive tract should require a close collaboration between pediatric immunologists and gastroenterologists, to optimize epidemiologic surveillance and management of ID.

Food intolerance related to gastrointestinal symptoms amongst adults living with bile acid diarrhoea: A cross-sectional study.

The role of food in managing bile acid diarrhoea (BAD) is poorly understood. The present study explored the prevalence of food intolerance amongst adults with BAD. The study comprised a cross-sectional survey of adults with BAD determined by the 75 selenium homotaurocholic acid test (SeHCAT) living in the UK. Participants anonymously completed an online questionnaire on 39 food items. Frequency of food in general affecting BAD symptoms, as well as frequencies of diarrhoea, abdominal pain, bloating, flatulence and consequential food avoidance after food item ingestion, were assessed. Food group avoidance was also assessed. There were 434 participants who completed the questionnaire between April and May 2021 of whom 80% reported moderate to severe chronic diarrhoea. Food intolerances were reported by 88.0% (95% confidence interval [CI] = 84.6-90.9) of participants. Diarrhoea was reported most frequently after take-away food, fish and chips, creamy sauces, cream and large quantities of fruit (range 41.0%-33.6%). Lowest frequencies were for potato, avocado, mango, watermelon and pear (range 3.7%-7.4%) for the foods listed in the questionnaire. Similar trends were found for abdominal pain, bloating, flatulence and consequential food avoidance. Symptom-triggering within 30 min of ingestion was more prevalence than after 30 min for almost all foods. Food group avoidance was highest for fatty foods (81.2%; 95% CI = 77.8-85.3) followed by dairy (53.9%; 95% CI = 49.1-58.7). Perceived food intolerance amongst adults with BAD and persisting diarrhoeal symptoms is high. Important triggers were meals with a higher fat content and higher-fat dairy products. Diets amongst those with persisting diarrhoeal symptoms may be overly restrictive.

Prevalence of Some Diarrhea Pathogens among under 5, in Wad Medani Pediatric Teaching Hospital, Gezira State, Sudan

Infections of gastrointestinal tract are the most frequent diseases worldwide. Infectious diarrhea is a major public health problem and remains one of the most important causes of morbidity and mortality among infants and children especially in developing countries. The symptoms of gastroenteritis include diarrhea and vomiting which may lead to severe dehydration and even death. The aim of this study was to identify some diarrheal pathogen among under five children attending to wad Medani Pediatric Teaching hospital during January 2021 to march 2022. Total of 384 stool samples were collected from children suffering from diarrhea and were tested using culture with biochemical test, direct examination by wet preparation and staining techniques. Moreover, screen Rotavirus by Ag ICT were used to determine their prevalence. The data were collected using questionnaire and analyzed using Statistical Package for the Social Sciences (SPSS). The results showed that the prevalence of pathogens were 196 samples (51%). The prevalence of pathogens showed that (29.6 %) was Giardia lamblia, (19.9%) was Cryptosporidium, (13.3%) was Rotaviruses, (12.2%) was Escherichia coli,( 9.7%) was Schigella species,( 8.7%) was Entamoeba histolytica and (6.6% )was Salmonella species. From those infected patients,( 56.1%) had fever, (76%) had vomiting. Also, (39.3%) were resides in urban while( 60.7%) resides in rural situation. About (42.9 % )had severe dehydration, (60% )acute diarrhea and (40%) chronic diarrhea , (87.8%) of children was take Rota vaccine and (70%) of mother not use soap to cleaning the children and think diarrhea not infectious disease it cause by teething. In conclusion most of diarrhea cause by parasitic infections mostly in poor family that not able to provide safety water and sanitation and low education of mother also some children suffer from malnutrition which decrease immunity and give chance to infection (Cryptosporidium).
 In Recommendation, health education about diarrhea disease in child important for mother to prevention, attention should be Payed proper to hygienic measure such as hand washing, safe disposal of feces and disinfection of contaminated surface to reduce the risk of infections agents transmission.

Intestinal Enterokinase Deficiency in Pediatrics

Abstract: Congenital enteropeptidase deficiency (CEP), also known as enterokinase deficiency. CEP is an uncommon autosomal recessive genetic disorder mostly characterized by severe chronic diarrhoea after delivery, hypoproteinemia, and failure to grow. Enteropeptidase activity is anticipated to play a significant role in protein digestion. For growth and appropriate development in newborns with a congenital lack of the enzyme, pancreatic enzyme replacement treatment or an amino acid combination must be given. Only 13 cases of enterokinase insufficiency have been recorded since it was originally characterized in 1969. Couples should be informed that prenatal screening is an option and that EKD has a favourable prognosis. However, if an EKD patient is born, parents should be aware of the feeding issue and offer the proper pancreatic exocrine secretion medication. One research found that all patients had been diagnosed as newborns 25 years ago. Even when the pancreatic-enzyme replacement was stopped, they appeared to lead regular lives as adults, free of gastrointestinal issues and with normal body weight. This can be explained by the fact that trypsin, once liberated from its precursor, encourages additional trypsinogen activation in a positive-feedback manner. Better pharmaceutical preparations such as enteric-coated minimicrospheres and delayed-release capsules are used for better results as it maintains the enzyme and prevents its breakdown by stomach acidity. This review aims to summarise current knowledge of pathophysiology, causes, and treatment of Intestinal Enterokinase Deficiency in Pediatrics

Use of Recombinant CP2 and CP23 Antigens of Cryptosporidium parvum for Serodiagnosis of Human Cryptosporidiosis

Cryptosporidium parvum is an important coccidian parasite infecting many mammals, including human. This parasite can manifest as chronic severe diarrhea in immunocompromised individuals, especially those with AIDS. The present study reports the recombinant production of rP2 and rP23 antigens of C. parvum as antigens for detecting human cryptosporidiosis using indirect ELISA tests. The coding sequences of rP2 and rP23 proteins were codon-optimized, commercially synthesized and sub-cloned in the pET28a expression vector. The expressed proteins were purified by Ni-NTA column chromatography and confirmed by Western blotting. The efficacy of rP2/rP23 proteins for serodiagnosis was evaluated by positive (n = 20) and negative (n = 20) human sera, confirmed by the Ziehl-Neelsen staining as the gold standard test. In ELISA test, the sera from C. parvum-infected patients reacted strongly to rP2/rP23. The sensitivity and specificity related to the diagnostic potential of rP2/rP23 in the ELISA assay were 100%. Our results showed that combination of rP23 and rP2 antigens in ELISA significantly increases the performance of C. parvum serodiagnosis in human cryptosporidiosis.

Use of Recombinant CP2 and CP23 Antigens of Cryptosporidium parvum for Serodiagnosis of Human Cryptosporidiosis

Cryptosporidium parvum is an important coccidian parasite infecting many mammals, including human. This parasite can manifest as chronic severe diarrhea in immunocompromised individuals, especially those with AIDS. The present study reports the recombinant production of recombinant (r)P2 and rP23 antigens of C. parvum as antigens for detecting human cryptosporidiosis using indirect ELISA tests.The coding sequences of rP2 and rP23 proteins were codon-optimized, commercially synthesized and sub-cloned in the pET28a expression vector. The expressed proteins were purified by Ni-NTA column chromatography and confirmed by Western blotting. The efficacy of rP2/rP23 proteins for serodiagnosis was evaluated by positive (n = 20) and negative (n = 20) human sera, confirmed by the Ziehl-Neelsen staining as the gold standard test.In ELISA test, the sera from C. parvum-infected patients reacted strongly to rP2/rP23. The sensitivity and specificity related to the diagnostic potential of rP2/rP23 in the ELISA assay were 100%.Our results showed that combination of rP23 and rP2 antigens in ELISA significantly increases the performance of C. parvum serodiagnosis in human cryptosporidiosis.

S2704 A New Protein Losing Enteropathy: Autoimmune Cryptolytic Enterocolitis

Introduction: Protein losing enteropathy (PLE) can be classified into erosive, non-erosive, and increased interstitial pressure PLE. Presenting signs are often chronic non-bloody diarrhea, anasarca, abdominal pain, and weight loss. We present a complex case of a PLE presentation with a novel diagnosis. Case Description/Methods: A 30-year-old woman with a history of migraines presented with severe abdominal pain and chronic diarrhea. She was on long-term combined estrogen-progestin oral contraceptive pills (OCP) and chronic high dose non-steroidal anti-inflammatory (NSAID) medications. She was exposed to mycoplasma pneumoniae one month prior to presentation, without other infectious exposures. Laboratory tests were notable for hemoglobin 6 g/dL, albumin 0.5 g/dL, stool pathogen PCR negative, and fecal calprotectin >3000µg/g. Extensive infectious work up only revealed Mycoplasma IgM+. Inflammatory markers and alpha-1 anti-trypsin clearance were elevated, and she was found to have warm autoimmune hemolytic anemia. CT angiography excluded ischemia and vasculitis (autoimmune serologies were negative), revealing diffuse enterocolitis, confirmed on magnetic resonance enterography with ileal ulcers. Endoscopic evaluation revealed diffuse superficial ulcerations terminal ileum and colon with diffuse mucosal sloughing. Histopathology revealed diffusely injured crypts with crypt drop-out and minimal inflammation, without any findings to suggest infection, inflammatory bowel disease (IBD) or autoimmune enteritis (Figure). Normal B-cell switching studies excluded common variable immunodeficiency (CVID). Due to profound anasarca and inability to tolerate oral intake, albumin infusions and total parenteral nutrition were started. There was minimal response to systemic or topical steroids. Diarrhea was mildly improved with albumin repletion, and she was empirically started on vedolizumab. Discussion: Given the absence of classic IBD findings, negative infectious and immunological testing, we present the first case of autoimmune cryptolytic enterocolitis, a histopathologic diagnosis of unclear etiology and pathogenesis. The patient has responded to vedolizumab infusions as an empiric treatment for an IBD-like entity. Nevertheless, supporting the autoimmune component of this entity, is a possible concomitant potential pathway of molecular mimicry in the setting of post-mycoplasma infection along with chronic high dose NSAID and OCP exposure.Figure 1.: Terminal Ileum and Sigmoid Colon with Diffuse Crypt Dropout.

S3377 Atypical Disseminated Mycobacterium Avium Complex: A Rare Case of Chronic Severe Diarrhea in a Patient with HIV

S3377 Atypical Disseminated Mycobacterium Avium Complex: A Rare Case of Chronic Severe Diarrhea in a Patient with HIV

S3444 Not All That Fistulizes Is Crohn’s Disease – Ischemic Jejunocolic Fistula

Introduction: Enterocolic fistulae lead to abnormal diversion of gastrointestinal contents from the small intestine to the colon, causing diarrhea and protein energy malnutrition. We describe a rare case of a jejunocolic fistula due to chronic mesenteric ischemia leading to severe chronic diarrhea. Case Description/Methods: A 40-year-old female with morbid obesity, nicotine dependence, type 2 diabetes mellitus was evaluated for epigastric pain and chronic diarrhea. She also had sitophobia and post-prandial urgency, with weight loss of 70 pounds over the last 6 months. She had been diagnosed with extensive thrombosis involving the abdominal aorta with extensions into the celiac artery, common hepatic artery, and left gastric artery, with evaluation revealing a JAK2 V617F mutant disorder. She was diagnosed with chronic mesenteric ischemia. For the evaluation of her diarrhea, she underwent an EGD with gastric and small bowel biopsies that was normal. CT enterography demonstrated an entero-colic fistula (jejunum to cecum). She underwent a colonoscopy which confirmed a 4 mm fistula in the cecum. Random colonic biopsies were normal, and biopsies from the fistula showed active chronic inflammation. Patient also has elevated calprotectin to 2600. Overall evaluation favored this isolated fistula in the setting of complex atherothrombotic disease to be from an ischemic origin rather than related to Crohn’s disease. The patient is currently being nutritionally optimized with plans for a surgical fistula takedown in the future. (Figure) Discussion: Enterocolic fistulae are complex conditions associated with high morbidity and mortality rates. Most fistulae occur following abdominal surgery, in the setting of infection or breakdown of an intestinal anastomosis due to ischemia, tension, or distal obstruction. Spontaneous fistula formation is uncommon (15-20% of cases), and causes include inflammatory bowel disease (specifically Crohn’s disease), diverticular disease, cancer, radiation enteritis and pancreatitis. Chronic ischemia is a very rare cause of spontaneous intestinal fistulization, with scant case reports described in literature. Enterocolic fistula can present with pain, diarrhea, and weight loss, and can be complicated by protein-energy malnutrition, abscesses, and sepsis. Management of the fistula depends on the underlying etiology, with importance given to nutritional optimization. Surgical takedown or endoscopic closure of fistulae remain a viable option in patients with localized disease.Figure 1.: CT enterography demonstrating a jejunocolic fistula (yellow arrow).

Mitchell-Riley Syndrome: Improving Clinical Outcomes and Searching for Functional Impact of RFX-6 Mutations.

Aims/HypothesisCaused by biallelic mutations of the gene encoding the transcription factor RFX6, the rare Mitchell–Riley syndrome (MRS) comprises neonatal diabetes, pancreatic hypoplasia, gallbladder agenesis or hypoplasia, duodenal atresia, and severe chronic diarrhea. So far, sixteen cases have been reported, all with a poor prognosis. This study discusses the multidisciplinary intensive clinical management of 4 new cases of MRS that survived over the first 2 years of life. Moreover, it demonstrates how the mutations impair the RFX6 function.MethodsClinical records were analyzed and described in detail. The functional impact of two RFX6R181W and RFX6V506G variants was assessed by measuring their ability to transactivate insulin transcription and genes that encode the L-type calcium channels required for normal pancreatic beta-cell function.ResultsAll four patients were small for gestational age (SGA) and prenatally diagnosed with duodenal atresia. They presented with neonatal diabetes early in life and were treated with intravenous insulin therapy before switching to subcutaneous insulin pump therapy. All patients faced recurrent hypoglycemic episodes, exacerbated when parenteral nutrition (PN) was disconnected. A sensor-augmented insulin pump therapy with a predictive low-glucose suspension system was installed with good results. One patient had a homozygous c.1517T>G (p.Val506Gly) mutation, two patients had a homozygous p.Arg181Trp mutation, and one patient presented with new compound heterozygosity. The RFX6V506G and RFX6R181W mutations failed to transactivate the expression of insulin and genes that encode L-type calcium channel subunits required for normal pancreatic beta-cell function.Conclusions/InterpretationMultidisciplinary and intensive disease management improved the clinical outcomes in four patients with MRS, including adjustment of parenteral/oral nutrition progression and advanced diabetes technologies. A better understanding of RFX6 function, in both intestine and pancreas cells, may break ground in new therapies, particularly regarding the use of drugs that modulate the enteroendocrine system.

Thymoma-associated autoimmune enteropathy with colonic stricture: a diagnostic and histological challenge.

Thymoma-associated autoimmune enteropathy is a rare paraneoplastic syndrome that is characterized by severe chronic diarrhea, malabsorption, and specific histological findings. Because of its rarity, it is difficult to diagnose. We describe an adult patient with protracted diarrhea and weight loss that developed recurrent sepsis and progressive colonic stenosis due to thymoma-associated autoimmune enteropathy. Ultimately, the diagnosis thymoma-associated autoimmune enteropathy was established by characteristic intestinal histology, anti-enterocytes antibodies, and thorax imaging. Radical thymectomy was performed without improvement. Therapy with azathioprine and infliximab induced clinical remission with complete recovery of the colonic stenosis.

Adult-Onset Autoimmune Enteropathy in an European Tertiary Referral Center.

INTRODUCTION:Adult-onset autoimmune enteropathy (AIE) is a rare cause of severe chronic diarrhea because of small intestinal villous atrophy. We report on patients with adult-onset AIE in an European referral center.METHODS:Retrospective study including patients diagnosed with AIE in the Amsterdam UMC, location VUmc, between January 2003 and December 2019. Clinical, serological, and histological features and response to treatment were reported. The specificity of antienterocyte antibodies (AEA) was evaluated by examining the prevalence of AEA in (i) controls (n = 30) and in patients with (ii) AIE (n = 13), (iii) celiac disease (CD, n = 52), (iv) refractory celiac disease type 2 (n = 18), and (v) enteropathy-associated T-cell lymphoma (EATL, n = 10).RESULTS:Thirteen AIE patients were included, 8 women (62%), median age of 52 years (range 23–73), and 6 (46%) with an autoimmune disease. AEA were observed in 11 cases (85%), but were also found in CD (7.7%), refractory celiac disease type 2 (16.7%), and EATL (20%). Ten patients (77%) were human leukocyte antigen DQ2.5 heterozygous. Total parenteral nutrition was required in 8 cases (62%). Steroids induced clinical remission in 8 cases (62%). Step-up therapy with rituximab, cyclosporine, infliximab, and cladribine in steroid-refractory patients was only moderately effective. Four patients died (31%), but 4 (31%) others are in long-term drug-free remission after receiving immunosuppressive treatment, including 1 patient who underwent autologous stem cell transplantation.DISCUSSION:Adult-onset AIE is a rare but severe enteropathy that occurs in patients susceptible for autoimmune disease. Four patients (31%) died secondary to therapy-refractory malabsorption, while immunosuppressive therapy leads to a long-lasting drug-free remission in one-third of patients.

Immune-mediated enteropathies: From bench to bedside.

Immune-mediated enteropathies are caused by excessive reactions of the intestinal immune system towards non-pathogenic molecules. Enteropathy leads to malabsorption-related symptoms and include (severe) chronic diarrhea, weight loss and vitamin deficiencies. Parenteral feeding and immunosuppressive therapy are needed in severe cases. Celiac disease has long been recognized as the most common immune-mediated enteropathy in adults, but the spectrum of immune-mediated enteropathies has been expanding. Histological and clinical features are sometimes shared among these enteropathies, and therefore it may be challenging to differentiate between them. Here, we provide an overview of immune-mediated enteropathies focused on clinical presentation, establishing diagnosis, immunopathogenesis, and treatment options.

Is Ileocolonoscopy Necessary When Evaluating Abdominal Pain and Nonbloody Diarrhea?

* Abbreviations: CRP — : C-reactive protein FGID — : functional gastrointestinal disorder IBD — : inflammatory bowel disease Chronic abdominal pain and diarrhea are common symptoms in children. In any given 6-month period, up to half of the children in the United States report persistent abdominal pain, which often leads to a medical evaluation.1–5 When evaluating children with chronic abdominal pain and diarrhea, clinicians have the challenge of determining how much of an evaluation is necessary because a functional gastrointestinal disorder (FGID) is most likely. Rome IV criteria (international guidelines used to define FGIDs) state that the diagnosis of an FGID can be supported when “after appropriate medical evaluation the symptoms cannot be attributed to another medical condition.”5 The central question is as follows: what is appropriate medical evaluation? Certainly the presence of “alarm” signs and symptoms (eg, weight loss, poor weight gain, poor linear growth, significant vomiting, chronic severe diarrhea, hematochezia, persistent right upper or lower quadrant pain, fever, unexplained anemia, family history of inflammatory bowel disease [IBD]) should prompt a full diagnostic evaluation.3 When should an extensive evaluation, including upper gastrointestinal endoscopy or ileocolonoscopy be done? These … Address correspondence to Jillian S. Sullivan, MD, MSCS, Department of Pediatrics, The University of Vermont Children’s Hospital, 111 Colchester Ave, Burlington, VT 05401. E-mail: jillian.sullivan{at}uvmhealth.org

A110 DGAT1 MUTATION OF LIPID TRAFFICKING ASSOCIATED WITH A RARE CASE OF CONGENITAL DIARRHEA

Abstract Background Congenital diarrheas and enteropathies (CODEs) are rare and cause severe chronic diarrhea in children under 2 years of age.1 Current genomic research has identified several monogenic defects resulting in epithelial disorders of nutrient and electrolyte transport, enzymes function, metabolism and trafficking. Aims To discuss a rare case of congential diarrhea. Methods Case Report. Results A 10-month-old Ashkenazi Jewish boy was referred to Pediatric Gastroenterology for loose stools and failure to thrive. Born at 27 weeks, he was a NICU inpatient for his first 3 months of life. Explosive loose stools were first noticed after discharge and treated as cow’s milk protein allergy. At aged 10 months he was admitted to his local hospital with irritability, abdominal distension, foul smelling loose stools and developmental delay. Despite an intake of 130kcal/kg/day he failed to gain weight (weight and length < 3rd centile). His abdomen was distended but there was no organomegaly on examination. On transfer to Sick Kids he underwent extensive work up with low albumin 24 g/L but normal CBC, amylase, lipase and IgA and anti-TTG negative. The lipid profile showed hypertriglyceridemia 2.98 mmol/L (normal <0.85), low HDL 0.81 mmol/L but normal total cholesterol. Low apoliprotein A1 0.79 g/L (0.92 - 1.96), low apoliprotein B 0.54 g (0.59 - 1.46) and vitamin E deficiency 9.6 umol/L (14.5 - 33.0). Normal fecal elastase (> 500 ug/g stool). Upper GI endoscopy showed duodenal villi blunting with non-specific chronic inactive duodenitis on histopathology. Due to ongoing poor weight gain he commenced TPN. A repeat endoscopy four weeks after admission revealed patchy villous blunting, crypt hyperplasia and enterocyte vacuolization. However, ultrastructural electron microscopy examination showed normal enterocyte brush border with well-formed microvilli with no inclusions or vesicular bodies. With a differential diagnosis of chylomicron retention disorder, abetalipoproteinemia or hypolipoproteinemia he was commenced on a low-fat diet with MCT feeds. A 72-hour fecal fat collection on this diet was within normal range 5.4 mmol/day (2–7). One year later his weight is now on 3rd centile and his albumin levels have normalized. However, triglycerides remain elevated. Whole exome sequencing identified two pathogenic variants in the DGAT1 gene; c.629_631delCCT, pSer210del and c751 + 2T>C, IVSB+2T>C. Conclusions Diacylglycerol acyltransferase (DGAT)1 catalyzes triglyceride biosynthesis.2 Loss of function DGAT1 gene mutations are described in several cases studies3,4 characterized by electrolyte transport–related diarrhea, protein-losing enteropathy and growth failure. Our cases adds to the understanding of the phenotypic and histological spectrum of DGAT1 mutations. Management strategies currently focus on growth with dietary lipid restriction, while substituting fat-soluble vitamins and essential fatty acids. Funding Agencies CAG