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Background Congenital diarrheal disorders (CDDs) are a rare group of enteropathies that typically present in the early few months of life and pose a diagnostic challenge. We aimed to analyze the clinical findings and outcome of infants with CDDs and share experience about genetic testing. Methods Demographic, clinical and genetic findings, and outcome of the patients (n = 24) with CDDs were recorded from hospital files. Results The onset of diarrhea was within the neonatal period in 45.8% of the patients. The most frequent causes of CDDs were defects in digestion, absorption and transport of nutrients and electrolytes (DATN) (n = 11, 45.8%) and defects in intestinal immune-related homeostasis (IIH) (n = 6, 25%). Fat malabsorption (n = 6) was the leading cause of defects in DATN. Extraintestinal manifestations including neurological involvement (25%) and renal involvement (20.8%) were common among the patients. Genetic analyses were performed for 16 patients (targeted gene analysis in 9, congenital diarrhea panel in 3, immune deficiency panel in 1 and whole-exome sequencing in 3 patients). Genetic diagnosis was achieved in 14 of 16 patients (87.5%) with therapeutic consequences in 8 of 16 patients (50%). During the follow-up, 6 patients (25%) died. Conclusion The percentage of undefined etiology decreased, and treatment of the patients improved with the increased number of genetic testing in patients with CDDs.

Vitamin D deficiency is a major cause of hypocalcemic seizures in infants. Chronic enteropathy can cause both malnutrition and vitamin deficiency disorders, such as celiac disease, in Western Caucasians. However, gluten-related disorders are considered uncommon in most Asian countries, and there have been no reports of any infant being diagnosed with a gluten-related disorder in Japan. Here, we describe a case where a Japanese infant, with non-celiac gluten sensitivity, presented with hypocalcemic seizures resulting from a vitamin D deficiency. In this case, an eight-month-old boy had an afebrile seizure, and blood tests revealed both hypocalcemia and prolonged prothrombin time resulting in his transfer to our hospital. The presence of fatty stools and evidence of multiple vitamin deficiencies indicated some form of fat malabsorption. His laboratory and histological findings showed enteropathy, and he was thus diagnosed with non-celiac gluten sensitivity. Therefore, he was treated with a gluten-free diet supplemented with vitamins. This case suggests that infants with a vitamin D deficiency caused by celiac disease or non-celiac gluten sensitivity should be carefully monitored when they are given oral supplements of vitamin D, to prevent any adverse side-effects associated with the varied roles of vitamin D in the immune response.

Hyperoxaluria results from either inherited disorders of glyoxylate metabolism leading to hepatic oxalate overproduction (primary hyperoxaluria), or increased intestinal oxalate absorption (secondary hyperoxaluria). Hyperoxaluria may lead to urinary supersaturation of calcium oxalate and crystal formation, causing urolithiasis and deposition of calcium oxalate crystals in the kidney parenchyma, a condition termed oxalate nephropathy. Considerable progress has been made in the understanding of pathophysiological mechanisms leading to hyperoxaluria and oxalate nephropathy, whose diagnosis is frequently delayed and prognosis too often poor. Fortunately, novel promising targeted therapeutic approaches are on the horizon in patients with primary hyperoxaluria. Patients with secondary hyperoxaluria frequently have long-standing hyperoxaluria-enabling conditions, a fact suggesting the role of triggers of acute kidney injury such as dehydration. Current standard of care in these patients includes management of the underlying cause, high fluid intake and use of calcium supplements. Overall, prompt recognition of hyperoxaluria and associated oxalate nephropathy is crucial, because optimal management may improve outcomes.

Long-term outcomes in children undergoing intestinal transplantation remain unclear. Seventy-one children underwent intestinal transplantation in our center from 1989 to 2007. We report on 10-year posttransplant outcomes with (group 1, n = 26) and without (group 2, n = 9) a functional graft. Ten-year patient and graft survival rates were 53% and 36%, respectively. Most patients were studying or working, one third having psychiatric disorders. All patients in group 1 were weaned off parenteral nutrition with mostly normal physical growth and subnormal energy absorption. Graft histology from 15 late biopsies showed minimal abnormality. However, micronutrient deficiencies and fat malabsorption were frequent; biliary complications occurred in 4 patients among the 17 who underwent liver transplantation; median renal clearance was 87 mL/min/1.73 m2 . Four patients in group 1 experienced late acute rejection. Among the 9 patients in group 2, 4 died after 10 years and 2 developed significant liver fibrosis. Liver transplantation and the use of a 3-drug regimen including sirolimus or mycophenolate mofetil were associated with improved graft survival. Therefore, intestinal transplantation may enable a satisfactory digestive function in the long term. The prognosis of graft removal without retransplantation is better than expected. Regular monitoring of micronutrients, early psychological assessment, and use of sirolimus are recommended.

Fat malabsorption associated with Roux-en-Y gastric bypass (RYGB) may contribute to elevated postprandial glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) after the procedure, leading to sustained weight loss and appetite reduction. This study investigated whether fat malabsorption via orlistat increases GLP-1 and PYY and if these increases would be proportional to changes in hunger and satiety. Five healthy participants received standardized meals with 120 mg orlistat or placebo in a randomized, double-blinded, crossover design for 3 days. On the final day, glucose, insulin, GLP-1, PYY3-36 and visual analogue scores for hunger and satiety were measured over a 14-hour period that included three meals. Fasting, 14-hour area under the curve (AUC) and meal-related AUC for glucose and insulin were similar, although postprandial increases in peak insulin and glucose were greater with orlistat. PYY3-36 , GLP-1, hunger and satiety were not different. In conclusion, short-term orlistat administration does not enhance postprandial GLP-1 or PYY3-36 or affect hunger or satiety in normal-weight individuals. Furthermore, fat malabsorption from RYGB is unlikely to mediate subsequent postprandial increases in GLP-1 and PYY.

Vitamin E (tocopherol) is a fat-soluble vitamin with antioxidant properties; it protects cellmembranes from oxidation and destruction, found in a variety of foods including oils, meat,eggs, and leafy vegetables. Their serums levels are strongly influenced by concentration of serumlipids, and do not accurately reflect tissue vitamin levels. Effective vitamin E levels arecalculated as the ratio of serum alpha-tocopherol per gram total lipids.Absorption of dietary vitamin E requires effective pancreatic exocrine function and fat absorption,unless provided in a synthetic water-soluble form. Also, a specific protein (alphatocopheroltransfer protein) is required for effective transport and use. Signs and symptoms ofvitamin E deficiency include hemolysis, neuromuscular disorders, ataxia, and peripheral neuropathy.Because of an abundance of tocopherols in the human diet, its deficiency is rare exceptin individuals with pancreatic insufficiency or other conditions causing substantial fat malabsorption,or protein-energy malnutrition and may be caused by rare genetic defects affectingvitamin E metabolism or transport. No syndrome of acute vitamin E toxicity has been described.In premature infants, high-dose vitamin E treatment was associated with increased riskfor sepsis. Chronic intake of supplements in excess of 400 IU daily has been associated with increasedrisk of hemorrhage and all-cause mortality.

Background Oxalate nephropathy is a potentially underestimated cause of kidney failure characterized by massive deposition of calcium oxalate crystals in the renal parenchyma. The prevalence and modes of presentation of this entity are ill-defined. Methods Here we report on the largest consecutive series of cases of adult oxalate nephropathy diagnosed on native kidney biopsies from January 2010 to December 2018 in the UCLouvain Kidney Disease Network. Results We screened 2265 native kidney biopsies and identified 22 cases (1%) of oxalate nephropathy. Patients had a mean age at diagnosis of 61 years (±20) and presented either with acute on chronic kidney disease (CKD) (62%) or with acute kidney injury (AKI) (38%). Mean serum creatinine at biopsy was 8.0 ± 4.5 mg/dl. Kidney biopsies showed abundant calcium oxalate crystal deposits, associated with acute interstitial nephritis and tubular necrosis, and variable degrees of interstitial fibrosis and tubular atrophy. Chronic pancreatitis and gastric bypass were the most common causes of oxalate nephropathy (48%). During a mean follow-up of 29 months, half of the patients (52%) progressed to kidney failure, all within the month following diagnosis. Higher serum creatinine level at presentation and interstitial fibrosis and tubular atrophy score were associated with progression to kidney failure. Conclusion Oxalate nephropathy is the cause of kidney disease in 1% of consecutive native kidney biopsies and typically presents as acute on CKD or AKI. The prognosis of the disease is poor, with a high rate of kidney failure within the first month after the diagnosis., Graphical abstract

Vitamin E is a powerful lipophilic antioxidant that protects membranes from lipid peroxidation, and consequently, oxidative damage. Oxidative stress plays a role in the development of neurodegenerative diseases. Vitamin E supplementation is recommended in patients with vitamin E deficiency due to fat malabsorption. The addition of vitamin E to the diet slows Alzheimer's disease progression and protects older patients against respiratory infections. Recent studies also point to the involvement of oxidative stress in the pathology of immune-mediated skin diseases, such as atopic dermatitis and psoriasis. We reviewed the available clinical trials that investigated the role of vitamin E supplementation in preventing and treating atopic dermatitis and psoriasis. Data from these studies point to a positive role of vitamin E supplementation in these diseases. Still, due to limitations in study design, further evidence is needed to reach a definite conclusion. This article is protected by copyright. All rights reserved.

Children with biliary atresia, particularly infants, are at high risk for malnutrition due to a multitude of factors including poor oral intake and intolerance of enteral feeding, fat malabsorption, abnormal nutrient metabolism, and increased caloric demand. Malnutrition and sarcopenia negatively impact outcomes in biliary atresia, leading to higher pre- and post-transplant morbidity and mortality. This review summarizes factors contributing to nutritional deficiencies in biliary atresia and offers an organized approach to the assessment and management of malnutrition in this vulnerable population.

Permanent Brooke ileostomy continues to be a treatment option for selected patients with inflammatory bowel disease and cancer. This case report describes the author’s 50-year experience living with Crohn’s disease and a Brooke ileostomy, including the psychosocial and dietary adaptations required and the management of common complications such as peri-stomal irritant dermatitis, food blockage, and acute infectious diarrhea. Cross-sectional studies indicate that the quality of life with an ileostomy is usually good, but adaptation to an ileostomy is a life-long process.

International audience; Objectives: Given a lack of a systematic approach to the use of breath testing in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimise its utility and safety. Methods: Nine clinical questions regarding methodology, interpretation, and specific indications of breath testing and treatment of carbohydrate malabsorption were addressed by members of the Gastroenterology Committee (GIC) of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). A systematic literature search was performed from 1983 to 2020 using PubMed, the MEDLINE and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes. During a consensus meeting, all recommendations were discussed and finalised. In the absence of evidence from randomised controlled trials, recommendations reflect the expert opinion of the authors. Results: A total of 22 recommendations were voted on using the nominal voting technique. At first, recommendations on prerequisites and preparation for as well as on interpretation of breath tests are given. Then, recommendations on the usefulness of H2-lactose breath testing, H2-fructose breath testing as well as of breath tests for other types of carbohydrate malabsorption are provided. Furthermore, breath testing is recommended to diagnose small intestinal bacterial overgrowth (SIBO), to control for success of Helicobacter pylori eradication therapy and to diagnose and monitor therapy of exocrine pancreatic insufficiency, but not to estimate oro-caecal transit time (OCTT) or to diagnose and follow-up on celiac disease. Conclusions: Breath tests are frequently used in paediatric gastroenterology mainly assessing carbohydrate malabsorption, but also in the diagnosis of small intestinal overgrowth, fat malabsorption, H. pylori infection as well as for measuring gastrointestinal transit times. Interpretation of the results can be challenging and in addition, pertinent symptoms should be considered to evaluate clinical tolerance.

We aimed to estimate the prevalence of exocrine pancreatic insufficiency (EPI) related fat malabsorptionto correlate it with measures of autonomic neuropathy in patients with T2DM from India.Patients with T2DM (cases; n = 118) and normo-glycaemic individuals (controls; n = 82) underwent anthropometry and biochemical evaluation at baseline. The 72-hours fecal fat excretion was estimated by the Van de Kamer's titration method. Autonomic neuropathy was evaluated using an automated analyzer.The prevalence of EPI related fat malabsorption in cases was 45% (n = 53; 72 hours mean fecal fat level = 22.7 ± 5.6 g/day). Dysfunctions in the parasympathetic nervous system (PNS; 86.7%; p 0.05), sympathetic nervous system (SNS; 92.4%; p 0.05), and both; PNS + SNS (83.1%; p 0.05) were significant. Amongst measures of PNS dysfunction, there was a significantly higher percentage of abnormal expiration: inspiration ratio (45.3%) and the 30:15 ratio (84.9%) (p 0.05) in patients with T2DM and EPI related fat malabsorption.In this cross-sectional cohort of Asian Indian patients with T2DM (n = 118), EPI related fat malabsorption correlates significantly with autonomic dysfunction in patients with T2DM. However, these preliminary data need to confirmed in trials with more robust design.

BACKGROUND Lipid malabsorption causes many health problems, for example stunting, a major worldwide issue. There has not been any assessment on the effectivity of lipid microscopic test in diagnosing lipid malabsorption. This research was aimed to study the effectivity of lipid microscopic test in detecting lipid malabsorption in children. METHODS This was a cross-sectional diagnostic study that evaluated the effectivity of lipid microscopic test using Sudan III against steatocrit test as the gold standard in diagnosing lipid malabsorption. The study was done in 68 children aged 6–60 months in Cipto Mangunkusumo Hospital, Jakarta. Results of lipid microscopic test were compared with that of steatocrit test among children with lipid malabsorption and normal children. The primary endpoints of this study are the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS A total of 68 children consisting of 41 boys and 27 girls were included, with a median age of 14.3 months. The most frequently found stool consistency was mushy (50%). The most common result of microscopic test, found in 42% of subjects, was positive 1. Sensitivity, specificity, PPV, and NPV of lipid microscopic test were 49.15%, 66.67%, 90.63%, and 16.67%, respectively. CONCLUSIONS Lipid microscopic test has a moderate sensitivity in diagnosing fat malabsorption and needs to be complemented with other methods such as steatocrit.

Obesity and obesity-related disorders are a global epidemic affecting over 10% of the world’s population. Treatment of these diseases has become increasingly challenging and expensive. The most effective and durable treatment for Class III obesity (body mass index ≥35 kg/m(2)) is bariatric surgery, namely, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy. These procedures are associated with increased circulating bile acids, molecules that not only facilitate intestinal fat absorption but are also potent hormones regulating numerous metabolic pathways. We recently reported on a novel surgical procedure in mice, termed distal gallbladder bile diversion to the ileum (GB-IL(dist)), that emulates the altered bile flow after RYGB without other manipulations of gastrointestinal anatomy. GB-IL(dist) improves oral glucose tolerance in mice made obese with high-fat diet. This is accompanied by fat malabsorption and weight loss, which complicates studying the role of elevated circulating bile acids in metabolic control. A less aggressive surgery in which the gallbladder bile is diverted to the proximal ileum, termed GB-IL(prox), also improves glucose control but is not accompanied by fat malabsorption. To better understand the differential effects achieved by these bile diversion procedures, an untargeted ultraperformance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM-MS) method was optimized for fecal samples derived from mice that have undergone bile diversion surgery. Utilizing the UPLC-IM-MS method, we were able to identify dysregulation of bile acids, short-chain fatty acids, and cholesterol derivatives that contribute to the differential metabolism resulting from these surgeries.

ObjectivesReliable pancreatic function tests in patients with chronic pancreatitis (CP) are needed. This cohort study identified malabsorption in people with CP compared with healthy people and then investigated short-term pancreatic enzyme replacement therapy (PERT) and fat malabsorption, nutrition

Chronic diarrhea in patients with neuroendocrine tumors (NET) may be caused by bioactive products of NET, bile acid malabsorption (BAM), ileal resection (IR) or steatorrhea. To quantitate BA and fat malabsorption in NET with diarrhea. Part of evaluation in medical oncology clinical practice, 67 patients [42F, 25 M; median age 64.0 y (17.0 IQR)] with well-differentiated NET and diarrhea underwent clinically indicated measurements of 48-h fecal BA [(FBA), fecal weight (normal 2337 µmol/48 h) or > 10% primary FBA or combination > 4% primary FBA plus > 1000 µmol total FBA/48 h. We also measured fecal elastase (for pancreatic insufficiency) in 13 patients. BAM was present in 48/52 (92%) patients with NET. There were significant correlations between total FBA and 48-h fecal weight (Rs = 0.645, P 10% in 69%. In 22 patients with no IR, 13/15 tested (87%) had BAM. Among 6 patients with pancreatic NET and no IR, 80% had BAM. Fecal fat was ≥ 15 g/day in 18/42 (43%). In 4/17 (24%) with IR 25 cm fecal fat was 44.0 (40.5) and 38.0 (38.0)g/day, respectively. A majority of patients with NET and diarrhea had BAM, even with

Children with intestinal failure on home parenteral nutrition are at risk of fat malabsorption and fat soluble vitamin deficiency. Fish oil containing mixed lipid emulsions (SMOFlipid®) with higher vitamin E content, have a theoretical risk of exceeding current recommendations for vitamin E dosing and, may influence other fat soluble vitamin status in these children. The aim of this study was to assess for fat soluble vitamin status in children on long-term home parental nutrition receiving a mixed lipid emulsion (SMOFlipid®) compared with those receiving traditional soy or soy/olive oil based (non- SMOFlipid®) lipid emulsions and whether this is influenced by the underlying cause of intestinal failure.Retrospective longitudinal study in a tertiary referral paediatric hospital of children on home parental nutrition during the period January 2000 to June 2019. Data was retrieved using medical and pharmacy records, laboratory database, and summarised using inferential statistics.111 patients (n = 58 female) received home parental nutrition in 121 discrete episodes (range 45-5329 days). N = 61 (55%) were diagnosed with anatomical short bowel syndrome, of which necrotising enterocolitis was the most common cause (n = 14). SMOFlipid® was used exclusively in n = 79 patients, non-SMOFlipid® exclusively in n = 19, and n = 13 changed from non-SMOFlipid® to SMOFlipid® during the study period. The median vitamin E level and vitamin E:lipid ratio were significantly higher for patients on SMOFlipid® compared to non-SMOFlipid® (27.9 vs 18.3 μmol/L respectively, p 0.001; 7.10 vs 4.00 μmol/mmol; p 0.001). Median vitamin A level was comparable (1.19 vs 1.12 μmol/L, p = 0.241), while median vitamin D level was significantly lower in the non-SMOFlipid® group consistent with mild deficiency (63.7 vs 43.0 nmol/L, p 0.001).The use of SMOFlipid® correlated with higher Vitamin E level in paediatric home parental nutrition patients. Lower vitamin D level appears to correlate with the use of non-SMOFlipid®. A larger prospective cohort is required to delineate any clinical significance from these findings.

Cystic fibrosis (CF) is a genetic disease affecting mucosal secretions. Most patients experience digestive symptoms, but the mechanisms are incompletely understood. Here we explore causes and consequences of slower gastrointestinal transit using magnetic resonance imaging (MRI).Twelve people with CF and 12 healthy controls, matched for age and gender, underwent MRI scans both fasted and after standardised meals over a period of 6.5 hours. Images were assessed for small bowel motility, longitudinal relaxation time (T1) of ascending colon chyme, chyme texture and appearance of the colon wall.Small bowel motility scores were significantly lower in CF than in healthy controls in the fasting state (CF median 40 arbitrary units IQR [31, 46] vs Control 86 a.u. [52, 106],P=0.034). This difference was less pronounced postprandially. Furthermore, ascending colon chyme T1was lower in CF than in controls (CF 0.59 s [0.38, 0.77] vs Control 0.79 s [0.55, 1.31],P=0.010). The difference in texture between small bowel and colon chyme, seen in health, was diminished in CF (difference in Haralick contrast 0.90 a.u. [0.38, 1.67] vs Control 2.11 a.u. [0.71, 3.30],P=0.010). Ascending colon mucosa in CF participants had an abnormal appearance compared to controls (Score 1-3, CF 2 [1, 3] vs Controls 1 [1, 1],P=0.019).Reduced small bowel motility and water content of ascending colon chyme are consistent with slower transit and constipation. MRI provides unique insights into chyme texture in the small bowel (suggesting bacterial overgrowth) and the appearance of the colon mucosa (suggesting altered mucus) in CF.Key point summary-People with cystic fibrosis (CF) have intrusive digestive symptoms and severe gut complications, but mechanisms are incompletely understood.-In this study, 12 people with CF were compared to healthy controls, undergoing repeated MRI scans before and after standardised meals.-Fasted small bowel motility is reduced in people with CF, consistent with slower transit. In addition, a reduced colonic chyme water content and abnormal appearance of small bowel and colonic chyme as well as colonic mucosa suggest small bowel bacterial overgrowth, fat malabsorption and abnormal mucus production-These MRI outcomes hold promise in the assessment of therapeutic interventions.

Vitamin E deficiency can be observed in patients with malabsorption syndromes or inherited diseases such as ataxia. It is unusual for it to be a result of dietary insufficiency due to its presence in a wide variety of foods. Patients with vitamin E deficiency can present with neuromuscular disorders such as ataxia, hyporeflexia, spinocerebellar syndrome, as well as loss of vibration and proprioceptive sensation. Herein, we are presenting a case in which a previously healthy adult with no family history of genetic defects and malabsorption syndrome presented with a characteristic sensory axonopathy associated with vitamin E deficiency without any evidence of fat malabsorption. Patient reported a markedly improvement of symptoms after three-month supplementation of vitamin E. The unique part of this case was that the patient presented with neuropathic pain associated with vitamin E deficiency without any family history of inherited deficiency or any malabsorption syndrome.

Bile acids are natural detergents that aid in the absorption of dietary lipids. Fatty acid binding protein 6 (Fabp6) is a component of the bile acid recovery system that operates in the small intestine. The aim of this study was to determine if Fabp6 deficiency causes dietary fat malabsorption. Wild‐type and Fabp6‐deficient mice were fed a Western‐style diet (WSD) or a reference low‐fat diet (LFD) for 10 weeks. The body weight gain, bile acid excretion, fat excretion, energy metabolism, and major gut microbial phyla of the mice were assessed at the end of the controlled diet period. Fabp6 −/− mice exhibited enhanced excretion of both bile acids and fat on the WSD but not on the LFD diet. Paradoxically, male Fabp6 −/− mice, but not female Fabp6 −/− mice, had greater adiposity despite increased fat excretion. Analysis of energy intake and of expenditure by indirect calorimetry revealed sex differences in physical activity level and respiratory quotient, but these did not account for the enhanced adiposity displayed by male Fabp6 −/− mice. Analysis of stool DNA showed sex‐specific changes in the abundance of major phyla of bacteria in response to Fabp6 deficiency and WSD feeding. The results obtained indicate that the malabsorption of bile acids that occurs in Fabp6 −/− mice is associated with dietary fat malabsorption on the high‐fat diet but not on the low‐fat diet. The WSD induced a sexually dimorphic increase in adiposity displayed by Fabp6 −/− mice and sexually distinct pattern of change in gut microbiota composition., Loss‐of‐function of Fabp6 in mice can cause fat malabsorption when fed a Western‐style diet, sex‐specific changes in the composition of gut microbiota and sexually dimorphic body weight gain.

Cystic fibrosis is the most common life-shortening genetic disease affecting Caucasians, clinically manifested by fat malabsorption, poor growth and nutrition, and recurrent sinopulmonary infections. Newborn screening programs for cystic fibrosis are now implemented throughout the United States and in many nations worldwide. Early diagnosis and interventions have led to improved clinical outcomes for people with cystic fibrosis. Newer cystic fibrosis transmembrane conductance regulator potentiators and correctors with mutation-specific effects have increasingly been used in children, and these agents are revolutionizing care. Indeed, it is possible that highly effective modulator therapy used early in life could profoundly affect the trajectory of cystic fibrosis lung disease, and primary prevention may be achievable.

During the last two decades, a large body of information on the events responsible for intestinal fat digestion and absorption has been accumulated. In particular, many groups have extensively focused on the absorptive phase in order to highlight the critical “players” and the main mechanisms orchestrating the assembly and secretion of chylomicrons (CM) as essential vehicles of alimentary lipids. The major aim of this article is to review understanding derived from basic science and clinical conditions associated with impaired packaging and export of CM. We have particularly insisted on inborn metabolic pathways in humans as well as on genetically modified animal models (recapitulating pathological features). The ultimate goal of this approach is that “experiments of nature” and in vivo model strategy collectively allow gaining novel mechanistic insight and filling the gap between the underlying genetic defect and the apparent clinical phenotype. Thus, uncovering the cause of disease contributes not only to understanding normal physiologic pathway, but also to capturing disorder onset, progression, treatment and prognosis.

Dietary Vitamin K is a well-known anti-hemorrhagic agent that plays an integral role in the coagulation pathway. Vitamin K is involved in synthesis of coagulation factors; II, VII, IX and factor X. Vitamin K deficiency leads to bleeding diathesis. Hemorrhages usually present in deep soft tissue, rather than mucosal or epithelial membranes, bleeding that is generally caused by disorders of platelets. Major causes of vitamin K deficiency include; medications and diseases involving fat metabolism with a resultant fat malabsorption. Warfarin and Cephalosporins are one of the commonly prescribed medications that lead to vitamin K deficiency. Disease affecting fat metabolism pathway, such as; diseases of the pancreas (cystic fibrosis), short gut syndrome and certain pathologies of the biliary tree. Vitamin K deficiency is more common in newborns. In adults it is uncommon because of its ubiquitous nature and the abundance of its sources. Hemorrhagic disorders in adults due to Vitamin K deficiency are not commonly encountered in practice. We are presenting a case of an adult who presented with a compartment syndrome secondary to a traumatic intramuscular bleeding. Our case highlights the importance of considering vitamin K deficiency in the differential diagnosis of unexplained hemorrhages resulting from a coagulopathy.

Cystic fibrosis is a chronic, life-shortening illness that affects multiple systems and results in frequent respiratory infections, chronic cough, fat malabsorption and malnutrition. Poor sleep is often reported by patients with cystic fibrosis. Although objective data to explain these complaints have been limited, they do show poor sleep efficiency and frequent arousals. Abnormalities in gas exchange are also observed during sleep in patients with cystic fibrosis. The potential impact of these abnormalities in sleep on health and quality of life remains largely unstudied. This review summarizes what is known about sleep in children with cystic fibrosis, and implications for clinical practice. This report also highlights new evidence on the impact of sleep problems on disease-specific outcomes such as lung function, and identifies areas that need further exploration.

Objectives: Pancreatic insufficiency (PI) and malabsorption of fats lead to reduced caloric intake, inability to maintain weight, and increased gastrointestinal symptoms. Thus, enteral nutrition (EN) is used in patients with cystic fibrosis (CF) and poor nutritional status. The current study evaluated safety, tolerability, and improvement of fatty acid (FA) status in red blood cell (RBC) membranes, a marker of long-term FA absorption, with an in-line digestive cartridge (RELiZORB) that hydrolyzes fat in enteral formula. Methods: Patients with CF receiving EN participated in a multicenter, 90-day open-label study during which RELiZORB was used with overnight EN. The primary endpoint was change over time in RBC uptake of docosahexaenoic acid (DHA)+ eicosapentaenoic acid (EPA). Gastrointestinal symptoms were collected to evaluate safety and tolerability. Several clinical and anthropometric parameters were also assessed throughout the study. Results: A total of 36 subjects completed the study with a mean age of 13.8 years, body mass index of 17.7 and 6.2 years mean use of overnight EN. Fat absorption significantly improved as shown by increased RBC levels of DHA+EPA, improved ω-6/ω-3 ratio, and increased plasma levels of DHA+EPA. RELiZORB use was not associated with any unanticipated adverse events. Conclusions: RELiZORB use was found to be safe, well tolerated, and resulted in increased levels of FAs in RBCs and plasma. This is the first prospective study to show EN can improve FA abnormalities in CF. Because improvement in omega-3 levels has been shown to help pulmonary and inflammatory status as well as anthropometric parameters in CF, RELiZORB may have important long-term therapeutic benefits in patients with CF.

Short bowel syndrome (SBS) occurs in patients who have had extensive resection. The primary physiologic consequence is malabsorption, resulting in fluid and electrolyte abnormalities and malnutrition. Nutrient digestion, absorption, and assimilation may also be diminished by disturbances in the production of bile acids and digestive enzymes. Small bowel dilation, dysmotility, loss of ileocecal valve, and anatomical changes combined with acid suppression and antimotility drugs increase the risk of small intestinal bacterial overgrowth, further contributing to malabsorption. Metabolic changes that occur in SBS due to loss of colonic regulation of gastric and small bowel function can also lead to depletion of calcium, magnesium, and vitamin D, resulting in demineralization of bone and the eventual development of bone disease. Persistent inflammation, steroid use, parenteral nutrition, chronic metabolic acidosis, and renal insufficiency may exacerbate the problem and contribute to the development of osteoporosis. Multiple factors increase the risk of nephrolithiasis in SBS. In the setting of fat malabsorption, increased free fatty acids are available to bind to calcium, resulting in an increased concentration of unbound oxalate, which is readily absorbed across the colonic mucosa where it travels to the kidney. In addition, there is an increase in colonic permeability to oxalate stemming from the effects of unabsorbed bile salts. The risk of nephrolithiasis is compounded by volume depletion, metabolic acidosis, and hypomagnesemia, resulting in a decrease in renal perfusion, urine output, pH, and citrate excretion. This review examines the causes and treatments of small intestinal bacterial overgrowth, bone demineralization, and nephrolithiasis in SBS.

Cystic fibrosis (CF) is an autosomal recessive, multi-organ disorder found predominantly among Caucasians. It classically presents in childhood with chronic productive cough, malabsorption causing steatorrhea, and failure to thrive. We present a 75-year-old female diagnosed with CF at the age of 57 years, which highlights the natural history and challenges in the diagnosis of atypical CF, including broadening physicians' respiratory differential diagnosis, limited patient symptoms, and late age of symptom onset.

Enteric hyperoxaluria is a distinct entity that can occur as a result of a diverse set of gastrointestinal disorders that promote fat malabsorption. This, in turn, leads to excess absorption of dietary oxalate and increased urinary oxalate excretion. Hyperoxaluria increases the risk of kidney stones and, in more severe cases, CKD and even kidney failure. The prevalence of enteric hyperoxaluria has increased over recent decades, largely because of the increased use of malabsorptive bariatric surgical procedures for medically complicated obesity. This systematic review of enteric hyperoxaluria was completed as part of a Kidney Health Initiative-sponsored project to describe enteric hyperoxaluria pathophysiology, causes, outcomes, and therapies. Current therapeutic options are limited to correcting the underlying gastrointestinal disorder, intensive dietary modifications, and use of calcium salts to bind oxalate in the gut. Evidence for the effect of these treatments on clinically significant outcomes, including kidney stone events or CKD, is currently lacking. Thus, further research is needed to better define the precise factors that influence risk of adverse outcomes, the long-term efficacy of available treatment strategies, and to develop new therapeutic approaches.

Background Vitamin D deficiency is highly prevalent in patients with inflammatory bowel disease (IBD). The question of whether vitamin D status is a contributory factor or a consequence of IBD, or maybe both, remains unanswered, and is confounded by the complexity of inflammation, IBD and vitamin D. Fat malabsorption has been proposed as a possible reason for deficiencies of vitamin D in IBD. The aim of this study was to further understanding of vitamin D deficiency in IBD by investigating possible causal relationships of fat malabsorption and inflammation on vitamin D levels in this complex context. Methods In a comparative, cross-sectional study in IBD patients, 25(OH)D was analysed by LCMS/MS. Serum β-carotene levels were used as a biomarker for fat malabsorption. Vitamin K1, another fat-soluble vitamin, was used to affirm a possible causative relation between β-carotene and vitamin D in case of fat malabsorption. β-carotene and vitamin K were measured in serum by HPLC. Inflammation was characterised by serum hsCRP Results 51 IBD patients (30f;20CD/18UC;45.3±16.3y; 21 with inflammatory activity) were enrolled. In patients with vs. without inflammation, serum 25(OH)D levels were significantly lower (26.5±14.6ng/mL vs. 36.8±12.6ng/mL, p0.05). 36/51 of the patients had low serum β-carotene levels, indicating steatorrhoea. Neither 25(OH)D (32.1.5±13.8ng/mL vs. 33.6±15.8ng/mL) nor vitamin K1 (1.3±0.5µg/L vs. 1.2±0.4µg/L) levels differed according to the presence vs. absence of steatorrhoea (p>0.05). Similarly, no correlation was found for 25(OH)D (r=0.024, p=0.875) or serum vitamin K1 (r=0.111, p=0.462) with β-carotene levels. On the other hand, 25(OH)D levels were significantly inversely correlated with hsCRP (r=-0.338, p=0.015), whereas vitamin K1(r=0.050, p=0.731) and β-carotene (r=-0.118, p=0.438) did not show a similar relation. Conclusion Vitamin D levels were confirmed to be related to inflammation in IBD. A lack of correlation with fat malabsorption, as indicated by β-carotene levels, or with steatorrhoea, was found for vitamin D and confirmed by measuring and comparing serum levels of an additional fat-soluble vitamin, K1. We conclude that low vitamin D levels in patients with IBD are related to inflammation rather than fat malabsorption.