Expanding the phenotypic and genotypic characteristics of trichohepatoenteric syndrome: a report of eight patients from five unrelated families.

BACKGROUND: Trichohepatoenteric syndrome (THES) is characterized by neonatal-onset intractable diarrhea. It often requires long-term total parenteral nutrition (TPN). In addition, other characteristic findings of the syndrome include growth retardation, facial dysmorphism, hair abnormalities, various immunological problems and other rare system findings. Two genes and their associated pathogenic variants have been associated with this syndrome: SKIC3 and SKIC2. METHODS AND RESULTS: In this case series, the clinical findings and molecular analysis results of a total of 8 patients from 5 different families who presented with persistent diarrhea and were diagnosed with THES were shared. Pathogenic variants were detected in the SKIC3 gene in 6 of our patients and in the SKIC2 gene in 2 patients. It was planned to compare the clinical findings of our patients with other patients, together with literature data, and to present yet-undefined phenotypic features that may be related to THES. In our case series, in addition to our patients with a novel variant, patient number 2 had a dual phenotype (THES and Spondyloepimetaphyseal dysplasia, sponastrime type) that has not been reported yet. Delay in gross motor skills, mild cognitive impairment, radioulnar synostosis, osteoporosis, nephropathy and cystic lesions (renal and liver) were observed as unreported phenotypic findings. CONCLUSIONS: We are expanding the clinical and molecular repertoire of the syndrome regarding patients diagnosed with THES. We recommend that the NGS (next-generation sequencing) multigene panel should be used as a diagnostic tool in cases with persistent diarrhea.

Chronic jejuno-colonic fistula and intestinal malabsorption due to multiple magnet ingestions: A case report and systematic review.

Magnet ingestion in children can lead to serious complications, both acutely and chronically. This case report discusses the treatment approach for a case involving multiple magnet ingestions, which resulted in a jejuno-colonic fistula, segmental intestinal volvulus, hepa-tosteatosis, and renal calculus detected at a late stage. Additionally, we conducted a literature review to explore the characteristics of intestinal fistulas caused by magnet ingestion. A six-year-old girl was admitted to the Pediatric Gastroenterology Department pre-senting with intermittent abdominal pain, vomiting, and diarrhea persisting for two years. Initial differential diagnoses included celiac disease, cystic fibrosis, inflammatory bowel disease, and tuberculosis, yet the etiology remained elusive. The Pediatric Surgery team was consulted after a jejuno-colonic fistula was suspected based on magnetic resonance imaging findings. The physical examination revealed no signs of acute abdomen but showed mild abdominal distension. Subsequent upper gastrointestinal series and contrast enema graphy confirmed a jejuno-colonic fistula and segmental volvulus. The family later reported that the child had swallowed a magnet two years prior, and medical follow-up had stopped after the spontaneous expulsion of the magnets within one to two weeks. Surgical intervention was necessary to correct the volvulus and repair the large jejuno-colonic fistula. To identify relevant studies, we conducted a detailed literature search on magnet ingestion and gastrointestinal fistulas according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We identified 44 articles encompassing 55 cases where symptoms did not manifest in the acute phase and acute abdomen was not observed. In 29 cases, the time of magnet ingestion was unknown. Among the 26 cases with a known ingestion time, the average duration until fistula detection was 22.8 days (range: 1-90 days). Fistula repairs were performed via laparotomy in 47 cases.

Pediatric Gastroenterology Research.

For several decades, before the 19th century, pediatric pathology was considered to be an annex of adult pathology and treated as a secondary matter in medical practice [...].

Advancing dentistry: fractal assessment of bone health in pediatric patients with celiac disease using dental images.

OBJECTIVES: To assess the effects of a gluten-free diet on bone structure in children with celiac disease using fractal analysis on panoramic radiographs. METHOD AND MATERIALS: A total of 49 patients with celiac disease aged 6 to 13 years, separated into two groups as previously and newly diagnosed, and a control group of 32 healthy individuals were evaluated. In previously and newly diagnosed patients with celiac disease, body mass index Z-scores were calculated, calcium, alkaline phosphatase, vitamin D3, and parathormone levels were measured, and bone mineral density Z-scores were obtained from dual energy x-ray absorptiometry. In all patients, the fractal dimensions of the right and left temporomandibular condyles were evaluated with the fractal analysis method on panoramic radiographs. RESULTS: The mean values of serum biomarker levels and the body mass index and bone mineral density Z-scores for both celiac groups were within the normal reference range. No statistically significant difference was determined between right and left condyle fractal dimensions values in the three groups examined. In terms of both right and left condyle fractal dimensions values, there was a statistically significant difference between groups. The highest fractal dimensions values were determined in the previously diagnosed group. CONCLUSIONS: Differences in fractal dimensions values were observed among patients with celiac disease following the gluten-free diet. Utilizing fractal analysis on panoramic radiographs can prove valuable for dental practitioners in evaluating bone mineral density due to its cost-effectiveness, easy accessibility, and reduced radiation exposure for patients, enabling them to provide comprehensive oral health care and potential early interventions for patients with celiac disease.

Accuracy Rate of Shear Wave Elastography in Detecting the Liver Fibrosis in Overweight and Obese Children with Hepatosteatosis.

OBJECTIVE: The aim of this study was to compare the accuracy rate of liver stiffness calculated by shear wave elastography with liver biopsy results in obese and overweight children. MATERIALS AND METHODS: Obese and overweight children between 3 and 18 years of age, who had hepatic steatosis and a healthy control group were included in this study. A blood sample was obtained for laboratory tests and shear wave elastography was performed for all subjects. Liver biopsies were performed only in patients with hepatosteatosis, providing permission for biopsy, and for whom the biopsy procedure was not contraindicated. RESULTS: A cohort of 142 children (78 overweight/obese and 64 healthy) was included in this study. Shear wave elastography values were significantly higher in the patient group as com- pared to the control group (34.0 vs. 8.2 kPa; P < .001). Obese children had higher elastog- raphy values compared to non-obese children (50.2 vs. 23.7 kPa, P < .001). No correlation was detected between fibrosis score and elastography values. Elastography increased with increasing weight (correlation coefficient: 0.334, P = .003) and body mass index (correlation coefficient: 0.364, P = .001). CONCLUSION: In obese and overweight patients, elastography values are higher than in healthy subjects as well as patients with liver fibrosis. Disease-specific cut-off, mean, and normal ref- erence range values should be defined with large-scale studies to improve interpretation of elastography values. Our results are contradictory in the determination of liver fibrosis with shear wave elastography in obese and overweight patients, thus further research with a larger patient population is recommended.

Can the Prognosis of COVID-19 Disease Be Determined by Fecal Markers and Cytokines?

The coronavirus disease 2019 (COVID-19) pandemic has affected the entire world, and has a variety of clinical presentations. The aim of this study is to determine the relationships of fecal cytokines and markers with the symptoms and prognosis of children with COVID-19 infection, and to identify noninvasive markers during follow-up. In a cohort of 40 COVID-19-positive children and 40 healthy controls, fecal cytokines and markers were examined in stool samples. A binary logistic model was used to assess the potential of cytokines as risk factors for hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported. A P-value <0.05 was accepted as statistically significant. Levels of fecal lysozyme, myeloperoxidase, hemoglobin, and interleukin-5 (IL-5) (P < 0.05) were significantly higher among the patients than controls. In a logistic regression analysis, fecal IL-2 (OR = 3.83; 95% CI: 1.44-15.92), IL-4 (OR = 2.96; 95% CI: 1.09-12.93), IL-5 (OR = 4.56; 95% CI: 1.18-27.88), IL-10 (OR = 2.71 95% CI: 1.19-7.94), interferon-gamma (IFN-γ) (OR = 4.03; 95% CI: 1.44-15.73), IFN-α (OR = 3.02; 95% CI: 1.08-11.65), calcium-binding protein B S100 (S100 B) (OR = 4.78; 95% CI: 1.31-27.82), neutrophil elastase (NE) 2 (OR = 4.07; 95% CI: 1.17-19.69), and matrix metalloproteinase 1 (MMP-1) (OR = 3.67; 95% CI: 1.1-18.82) levels were significantly higher in hospitalized patients with COVID-19 infection than outpatients. We demonstrated that various fecal cytokines and markers were increased in patients who had COVID-19. Fecal IL-2, IL-4, IL-5, IL-10, IFN-γ, IFN-α, S100 B, NE, and MMP-1 levels were significantly elevated in hospitalized patients. We suggest that the fecal and serum levels of cytokines could be used to predict the prognosis of COVID-19 disease, although more studies are needed to confirm this.

COmparisoN of TastES of Available NutriTional integrated or non-integrated formulas for infants older than 1 year of age with cow's milk allergy: A multicenter, prospective, single blind, cross-sectional observational clinical study (CONTEST Study).

Palatability of the infant formulas lacking cow milk protein formulas is reported by parents to be an important drawback. The purpose of this study is to examine decisions made by mothers of infants having cow milk protein allergy, and physicians concerning the palatability of unflavored extensively hydrolyzed formulas and amino acid-based formulas. We conducted a multi-center, randomized, single-blinded, observational taste study involving 149 pediatricians from gastroenterology and allergy subspecialties at 14 tertiary healthcare units from different regions of Turkey and involving 94 mothers of infants with cow milk protein allergy. Blinding was performed for seven formulas available in the market, which were the most commonly prescribed for feeding: four AAFs (Neocate-Numil®, Aptamil Pregomin AS-Numil®, Alfamino-Nestle®, Comidagen-Mamma®), one AAF specifically designed to address the growing nutritional and lifestyle needs of children >1 year (Neocate Junior-Numil®), 2 eHFs (Bebelac Pepti Junior-Numil®, Similac Alimentum-Abott®). Considering all three formula characteristics, Neocate junior-Numil® ranked as the number 1 product among seven products by mothers (63.8%) and physicians (69.8%). The ratings of mothers were significantly higher than the physicians (8.1 points and 6.1 points, respectively; p < 0.001). No difference was found in terms of taste, smell, and appearance for Neocate junior-Numil® between the mothers' and physicians' ratings. Since caregivers have responsibility for careful selection of replacement products for infants with cow milk protein allergy, it is noteworthy that increased awareness and confidence in the palatability characteristics of these products should motivate mothers and physicians to comply with replacement treatment in the long term.

Investigation of Thiol/Disulfide Homeostasis and Ischemia-Modified Albumin Levels in Children with Wilson Disease.

BackgroundThe aim of the present study was to assess thiol/disulfide homeostasis (TDH) parameters and ischemia-modified albumin (IMA) levels in children with Wilson Disease (WD) and to compare them to healthy controls. Methods: Based on the inclusion and exclusion criteria, fifteen children with WD and twenty-nine healthy children were enrolled, and serum thiol/disulfide and IMA levels were compared between groups. Results: The mean values of native and total thiols were significantly lower in the WD group than in the control group. The mean value of disulfide was significantly higher in the WD group than in the control group. The mean percentages of disulfide/total thiol and native thiol/total thiol were higher in the WD group than in the control group. The IMA value was also higher in the WD group than in the control group. Conclusion: The present study demonstrating altered thiol/disulfide parameters indicates increased oxidative stress in children with WD.

The Role of Telehealth Services in Children with Cystic Fibrosis During Coronavirus Disease 2019 Outbreak.

Objectives:This study aimed to monitor the health and nutritional status of pediatric cystic fibrosis (CF) patients via telehealth services during the novel coronavirus disease 2019 (COVID-19). Additional aims were to determine the level of anxiety in the patients and their caregivers and to determine the COVID-19 transmission status among CF patients.Materials and Methods:The CF team supported the patients via remote contact. During telehealth services interviews, in addition to obtaining information about the patients' anthropometric measurements, health status, and CF-related complaints, the State-Trait Anxiety Inventory (STAI) was administered to the patients and controls. The Hospital Anxiety and Depression Scale (HAD) was administered to their caregivers.Results:The study included 144 pediatric CF patients (74 males and 70 females). Mean age of the patients was 8.9 years. In all, 42 (29.2%) of the patients were tested for COVID-19, of which 4 were positive. The mean STAI score was significantly lower in the patient group than in the control group (p < 0.001). The mean HAD anxiety score was significantly higher in the caregivers of the CF patients, compared to the caregivers of the controls (p = 0.005). In addition, the mean HAD depression score was significantly higher in the caregivers of the CF patients (p < 0.001).Conclusions:Telehealth is an innovative method for providing health care services while maintaining social distance and avoiding the risk of exposure and spread of COVID-19. Telehealth services reduce patient and parental anxiety and increase the level of confidence in managing CF-related complications.

Recommendations for Clinical Decision-making in Children with Type 1 Diabetes and Celiac Disease: Type 1 Diabetes and Celiac Disease Joint Working Group Report

It is well-known that in children with type 1 diabetes (T1D), the frequency of Celiac disease (CD) is increased due to mechanisms which are not fully elucidated but include autoimmune injury as well as shared genetic predisposition. Although histopathologic examination is the gold standard for diagnosis, avoiding unnecessary endoscopy is crucial. Therefore, for both clinicians and patients' families, the diagnosis of CD remains challenging. In light of this, a joint working group, the Type 1 Diabetes and Celiac Disease Joint Working Group, was convened, with the aim of reporting institutional data and reviewing current international guidelines, in order to provide a framework for clinicians. Several controversial issues were discussed: For CD screening in children with T1D, regardless of age, it is recommended to measure tissue transglutaminase-immunoglobulin A (tTG-IgA) and/or endomysial-IgA antibody due to their high sensitivity and specificity. However, the decision-making process based on tTG-IgA titer in children with T1D is still debated, since tTG-IgA titers may fluctuate in children with T1D. Moreover, seronegativity may occur spontaneously. The authors' own data showed that most of the cases who have biopsy-proven CD had tTG-IgA levels 7-10 times above the upper limit. The decision for endoscopy based solely on tTG-IgA levels should be avoided, except in cases where tTG-IgA levels are seven times and above the upper limit. A closer collaboration should be built between divisions of pediatric endocrinology and gastroenterology in terms of screening, diagnosis and follow-up of children with T1D and suspicious CD.

The frequency of and factors affecting functional gastrointestinal disorders in infants that presented to tertiary care hospitals.

This study aimed to determine the prevalence of infantile functional gastrointestinal disorders (FGIDs) based on Rome IV diagnostic criteria, and to determine the associated patient demographic and nutritional characteristics. A total of 2383 infants aged 1-12 months which were evaluated by 28 general pediatricians and pediatric gastroenterologists on the same day at nine tertiary care hospitals around Istanbul, Turkey, between November 2017 and March 2018, were included in the study. Patients included consulted the pediatric outpatient clinics because of any complaints, but not for vaccines and/or routine well child follow-ups as this is not part of the activities in the tertiary care hospitals. The patients were diagnosed with FGIDs based on Rome IV diagnostic criteria. The patients were divided into a FGID group and non-FGID group, and anthropometric measurements, physical examination findings, nutritional status, risk factors, and symptoms related to FGIDs were evaluated using questionnaires. Among the 2383 infants included, 837 (35.1%) had ≥1 FGIDs, of which 260 (31%) had already presented to hospital with symptoms of FGIDs and 577 (69%) presented to hospital with other symptoms, but were diagnosed with FGIDs by a pediatrician. Infant colic (19.2%), infant regurgitation (13.4%), and infant dyschezia (9.8%) were the most common FGIDs. One FGID was present in 76%, and ≥2 FGIDs were diagnosed in 24%. The frequency of early supplementary feeding was higher in the infants in the FGID group aged ≤6 months than in the non-FGID group (P = 0.039).Conclusion: FGIDs occur quite common in infants. Since early diversification was associated with the presence of FGIDs, nutritional guidance and intervention should be part of the first-line treatment. Only 31% of the infants diagnosed with a FGID were presented because of symptoms indicating a FGID. What is Known: • The functional gastrointestinal disorders (FGIDs) are a very common disorder and affect almost half of all infants. • In infants, the frequency of FGIDs increases with mistakes made in feeding. When FGIDs are diagnosed in infants, nutritional support should be the first-line treatment. What is New: • This study shows that only a third of children presented to hospital because of the symptoms of FGIDs, but pediatricians were able to make the diagnosis in suspected infants after appropriate evaluation. • The early starting of complementary feeding (<6 months) is a risk factor for the development of FGIDs.

The effects of nutritional status and intervention on pulmonary functions in pediatric cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF) causes malabsorption of nutrients that exacerbate pulmonary problems. Nutritional interventions can improve pulmonary functions. We aimed to evaluate the effects of nutritional intervention in CF patients with malnutrition, and to determine if there is a correlation between nutritional status and pulmonary functions. METHODS: The study included 143 CF patients (67 females) with a mean 2 year follow-up time. Patients' sociodemographic data, presenting symptoms and history were recorded. Height-for-age, weight-for-age, weight-for-length/height (WFL/H), and body mass index (BMI) were calculated in all patients. Patients were grouped as well nourished, mild malnutrition, moderate malnutrition, and severe malnutrition. These four groups were compared in terms of pulmonary function test results, lung infections, and the hospitalization rate. RESULTS: Among the patients with a WFL/H or BMI z-scores that decreased, the frequency of lung infection was 74.1% and the hospitalization rate was 40.7%, versus 34% and 12.3%, respectively among the patients with a WFL/H or BMI z-scores that increased. The difference was significant (P = 0.02 and P = 0.01, respectively). The difference in bacterial lung infections differed significantly between the four nutritional status groups (P = 0.002). Patients in the well-nourished group had significantly higher pulmonary function test scores than the other groups. The forced expiratory volume in the first second differed significantly between the patients with and without an increase in the WFL/H or BMI z-scores (P = 0.001). CONCLUSIONS: The appropriate nutritional intervention to pediatric CF patients with malnutrition, decrease the frequency of lung infections, and improve respiratory function.

Prevalence and Clinical Features of Celiac Disease in Healthy School-Aged Children.

BACKGROUND/AIMS: The aim of this study was to determine the prevalence of celiac disease (CD) in healthy school-aged children in the northern region of Cyprus and to investigate the existence of potential markers that may accompany CD. This is the first study to measure the prevalence of CD in the northern region of Cyprus. METHODS: This study included 3792 school-aged children who were between the ages of 6 and 10 years between January 2015 and October 2016. CD was screened using total serum IgA, IgA anti-tissue transglutaminase (tTG), and IgA antiendomysial (EMA) antibodies. Subjects with selective IgA deficiency were further tested for IgG-tTG. Small intestinal biopsies were performed on all subjects with tTG antibody positivity. Risk factors and symptoms related to CD were evaluated using questionnaires in both the CD and control groups. RESULTS: Of the 3792 subjects, 39 were antibody positive (IgA-tTG was positive only in 14 subjects, IgA-tTG plus IgA-EMA in 21 subjects, and IgG-tTG in 4 subjects). IgA deficiency was detected in 11 subjects (0.29%). IgG-tTG was positive in 4 subjects with IgA deficiency (36.3%). Intestinal biopsies were performed on 28 of the 39 seropositive subjects. The biopsy findings of 15 children were consistent with CD (IgA-tTG positive in 3, IgA-tTG and IgA-EMA positive in 10, and IgG-tTG positive in 2). Thus, biopsies confirmed CD in 1:256 children (0.39%). CONCLUSIONS: Our study, which is the first study of school-aged children from the northern region of Cyprus, revealed that CD is a prevalent disease in this region.

Evaluation of malnutrition development risk in hospitalized children.

OBJECTIVES: Many screening methods, such as the Screening Tool Risk on Nutritional Status and Growth (STRONGkids) and the Pediatric Yorkhill Malnutrition Score (PYMS), have been developed to detect malnutrition in pediatric patients. We aimed to explore the prevalence of malnutrition risk in hospitalized children via symptoms and identification of contributing factors, and to examine the efficacy of malnutrition screening tools for hospitalized children. METHODS: STRONGkids and PYMS were applied to 1513 inpatients at 37 hospitals in 26 cities from different regions of Turkey. Physical measurements were collected at hospital admission and at discharge. z-Scores of height-for-age, weight-for-age, weight-for-height, and body mass index-for-age were calculated. RESULTS: Overall, 1513 patients were included in the study. A body mass index standard deviation score of less than -2 was present in 9.5% of the study population at hospital admission, whereas 11.2% of the participants had a weight-for-length/height score of less than -2 at hospital admission. According to STRONGkids results, the proportion of the patients with an underlying chronic disease was higher for the patients at high risk of malnutrition than for the patients at medium or low risk (91% compared with 47% or 45%, respectively). PYMS results indicated that patients at high risk of malnutrition have more chronic diseases (75%) than the patients at medium or low risk of malnutrition (55% and 44%, respectively). CONCLUSIONS: Use of anthropometric measurements in addition to screening tools to identify hospital malnutrition (such as PYMS, STRONGkids) will prevent some nutritional risk patients from being overlooked.

Role of RDW in Prediction of Burn after Caustic Substance Ingestion.

A quantifiable, quick, inexpensive and reproducible predictor is needed to decide if caustic substance ingestion results in burn regardless of the symptoms. A multicenter cohort study was conducted to investigate the predictive value of red cell distribution width (RDW) in detecting the esophageal burns. The data of 174 patients were retrospectively analyzed. Eleven patients were excluded due to inability to define the substance ingested. Complete blood count (CBC) was taken at admission, and an esophagogastroduodenoscopy was performed within the first 12-24 h in all patients, regardless of their symptoms. The age and gender of the patients, the types of substances ingested, the parameters in the CBC and the severity of the esophageal injury were correlated. Esophageal burns were diagnosed in 38 of 163 patients (23.3%). The risk of esophageal burn with RDW values below 12.20 was significantly lower. Multivariate analysis showed that RDW was the most significant predictor of esophageal burn (p = 0.000, odds ratio (OR) 7.74 (95% confidence interval (CI), 3.02-19.9)). Receiver operating characteristic (ROC) curve analysis demonstrated 84.2% sensitivity at a cut-off value of 12.20 for RDW. The results showed that CBC parameters could avoid unnecessary esophagogastroduodenoscopy. The RDW values regardless of the symptomatology is a good predictor of esophageal burns, and an RDW value over 12.20 shows the increased risk of esophageal burn.

Is There a Causal Relationship between Intussusception and Food Allergy?

Although intussusception and food allergy are common health problems in childhood, the relation between these two diseases remain obscure. The aim of this study is to investigate the relationship between food allergy and intussusception, and the factors associated with both. Patients diagnosed with intussusception by the Brighton Collaboration Intussusception Working Group criteria were prospectively investigated for food allergy per the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Guideline. They were analyzed per demographic features, clinical, physical and laboratory findings. There were eight (38.1%) patients diagnosed with food allergy, while 13 (61.9%) patients were non-allergic. The mean number of days of presenting symptoms was 1.13 days in the allergy group and 7.85 days in the non-allergy group. The mean number of intussusception attacks was 1.63 in the allergy group while 1 in the non-allergy group (p < 0.05, relative risk (RR) = 2.6). In the allergy group, one (13%) patient was followed up, six (75%) patients were reduced with pneumatic and one (13%) patient reduced manually. In the non-allergy group, four (31%) patients were followed up, six (46%) patients were reduced with pneumotic, one (7%) patient was reduced manually, and resection anastomosis was performed in two (15%) patients. Food allergy is an unrecognized associated factor for intussusception patients, which increases the risk for recurrence. Due to the small patient population, these results should be interpreted with caution.

CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis.

BACKGROUND: Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies. METHODS: We studied 11 patients with abdominal pain and diarrhea caused by early-onset protein-losing enteropathy with primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease; the disorder followed an autosomal recessive pattern of inheritance. Whole-exome sequencing was performed to identify gene variants. We evaluated the function of CD55 in patients' cells, which we confirmed by means of exogenous induction of expression of CD55. RESULTS: We identified homozygous loss-of-function mutations in the gene encoding CD55 (decay-accelerating factor), which lead to loss of protein expression. Patients' T lymphocytes showed increased complement activation causing surface deposition of complement and the generation of soluble C5a. Costimulatory function and cytokine modulation by CD55 were defective. Genetic reconstitution of CD55 or treatment with a complement-inhibitory therapeutic antibody reversed abnormal complement activation. CONCLUSIONS: CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55. (Funded by the National Institute of Allergy and Infectious Diseases and others.).