Engin Tutar

Visual loss and idiopathic intracranial hypertension in children with Alagille syndrome.

Background: Alagille syndrome (AGS) is an autosomal dominant, multisystem disorder defined by developmental abnormalities of the liver, heart, eye and skeleton. Although visual problems are recognised, the severity of visual loss and its link with idiopathic intracranial hypertension (IIH) has not been reported. Aim: To review the incidence of visual loss and IIH in children with AGS managed at a National Paediatric Liver Unit between 1989 and 2004. Subjects and Methods: Retrospective case note review of children who fulfilled criteria for diagnosis of AGS and had an ophthalmic examination by a paediatric ophthalmologist. Results: Fifty-five children with AGS were evaluated. Of these, 41 children fulfilled diagnostic criteria and had a documented ophthalmic examination. Six children had undergone liver transplantation. Three children had a definite diagnosis of IIH, 2 of whom developed postliver transplant. All 3 were treated medically, but 1 child with IIH required lumboperitoneal shunting. All 3 children with definite IIH have normal vision after treatment. Another child with probable undiagnosed IIH has bilateral optic atrophy and is registered blind. Two children with AGS are registered partially sighted, one with rod cone dystrophy and the other with pigmentary retinopathy and right disc atrophy. Summary: Although visual abnormalities are well described in children with AGS, a minority of children have significant progressive visual loss. Idiopathic intracranial hypertension has been identified as a potentially treatable precipitating factor. Conclusions: We recommend annual fundoscopy in the follow-up of children with AGS to facilitate early detection and appropriate management of IIH to prevent visual loss.

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.)

Sequential therapy versus standard triple therapy for Helicobacter pylori eradication in children: any advantage in clarithromycin-resistant strains?

Objective There has been a marked decrease in the eradication rates of Helicobacter pylori infection with standard triple therapy worldwide. Hence, sequential therapy has gained attention as a promising treatment during the last few years. This study was carried out to compare the efficacy of sequential versus standard triple therapy in the context of clarithromycin (CLA) resistance. Materials and methods In this study, children between 3 and 18 years of age, who had documented H. pylori infection, were randomized to receive either standard triple or sequential therapy. H. pylori eradication was ascertained using the 13C-urea breath test 4–6 weeks after the completion of the treatment. Real-time PCR was performed on gastric biopsy samples for assessment of CLA resistance. Results In all, 148 children (median age: 12.18±3.51 years) were recruited randomly into the study. The intention-to-treat eradication rates were 50% (37/74) for the sequential treatment group and 52.7% (39/74) for the standard triple treatment group (P=0.87). A total of 136 children completed the study. The per-protocol eradication rates were 56% (37/66) and 55.7% (39/70) for sequential and standard triple therapy groups, respectively. CLA resistance was assessed and 113 children were included in the final analysis. Of 113 participants, 53 were in the sequential treatment group and 60 were in the standard triple treatment group. The success rates of the respective therapies (29/53=54.7% in sequential, 33/60=55% in standard therapy) were similar (P=0.98). CLA resistance was detected in 29 (25.7%) of the patients. Eradication rates with sequential therapy in CLA susceptible and resistant cases were 60.5% (23/38) and 40% (6/15), respectively (P=0.23). The corresponding figures for the standard triple treatment group were 63% (29/46) and 28.6% (4/14) (P=0.033). Although a higher eradication rate was observed in CLA-resistant cases with sequential therapy, the difference did not reach statistical significance (P=0.69). Conclusion In this study, standard triple treatment failed to eradicate H. pylori infection in the majority of the children, and sequential therapy offered only a small advantage over standard triple therapy in the eradication of CLA-resistant strains.

Endoscopic and Histopathologic Findings Associated with H. pylori Infection in Very Young Children

Most of the individuals infected with H.xa0pylori acquire the infection early in life. However, there is limited data regarding endoscopic and histopathologic findings of H.xa0pylori infection when it is acquired during infancy. The aim of this study was to investigate the H.xa0pylori-related endoscopic and histopathological findings in children younger than 2xa0years of age. One hundred and fifty-two infants who underwent upper gastrointestinal endoscopy were included in the study. The diagnosis of H.xa0pylori infection was based on histopathology and a positive rapid urease test. Forty of 152 (26.3%) infants were infected with H.xa0pylori, and 65% of the infected infants had histopathologic gastritis. There were no clinical or endoscopic findings suggestive of H.xa0pylori infection. No correlation could be found between the density of H.xa0pylori and the severity of gastritis. H.xa0pylori infection is associated with various degrees of gastritis in more than half of the infected infants. Since the likelihood of normal histopathology is rare in H.xa0pylori-infected infants, its long-term complications should be cautiously followed up in endemic areas.

Gastrointestinal Manifestations in Children with Primary Immunodeficiencies: Single Center: 12 Years Experience

Background: It has been reported that 5–50% of patients with primary immune deficiencies (PID) may present with or develop gastrointestinal (GI) manifestations. Objective: This study was aimed at analyzing GI and related endoscopic, histopathological findings in children with PID. Methods: Children with PID who were evaluated by endoscopy between 2005 and 2016 were enrolled in this study. Demographic data, growth parameters, signs and symptoms at diagnosis were obtained. Results: Of 425 children with PID, 195 had GI manifestations. Forty-seven of 195 children required endoscopic investigation, 30 (63.8%) were male, and the mean age was 7.7 ± 5 years. The rate of consanguinity was 61.7%, and the most common symptom was chronic diarrhea (57.4%). Seventy-two percent of the patients were malnourished. Giardia intestinalis was detected in 4, and Helicobacter pylori was confirmed in 8/45 (17.7%) patients. Non-celiac villous flatting was discovered in 15.5% of patients. Twelve patients were diagnosed as having immunodeficiency associated inflammatory bowel disease (IBD)-like colitis. Conclusions: PID may present with GI manifestations or develop during the course of the disease. Investigating immunodeficiency in patients with atypical GI symptoms can provide an appropriate therapeutic option, and an improved quality of life, particularly in populations with a high rate of consanguinity.