CARMIL2 Deficiency Presenting as Very Early Onset Inflammatory Bowel Disease.

BACKGROUND: Children with very early onset inflammatory bowel diseases (VEO-IBD) often have a refractory and severe disease course. A significant number of described VEO-IBD-causing monogenic disorders can be attributed to defects in immune-related genes. The diagnosis of the underlying primary immunodeficiency (PID) often has critical implications for the treatment of patients with IBD-like phenotypes. METHODS: To identify the molecular etiology in 5 patients from 3 unrelated kindred with IBD-like symptoms, we conducted whole exome sequencing. Immune workup confirmed an underlying PID. RESULTS: Whole exome sequencing revealed 3 novel CARMIL2 loss-of-function mutations in our patients. Immunophenotyping of peripheral blood mononuclear cells showed reduction of regulatory and effector memory T cells and impaired B cell class switching. The T cell proliferation and activation assays confirmed defective responses to CD28 costimulation, consistent with CARMIL2 deficiency. CONCLUSION: Our study highlights that human CARMIL2 deficiency can manifest with IBD-like symptoms. This example illustrates that early diagnosis of underlying PID is crucial for the treatment and prognosis of children with VEO-IBD.

Magnetic resonance enterography in pediatric celiac disease / A enterografia por ressonância magnética na doença celíaca pediátrica

Abstract Objective: To assess if magnetic resonance enterography is capable of showing evidence/extent of disease in pediatric patients with biopsy-proven celiac disease by comparing with a control group, and to correlate the magnetic resonance enterography findings with anti-endomysial antibody level, which is an indicator of gluten-free dietary compliance. Methods: Thirty-one pediatric patients (mean age 11.7 ± 3.1 years) with biopsy-proven celiac disease and 40 pediatric patients as a control group were recruited in the study. The magnetic resonance enterography images of both patients with celiac disease and those of the control group were evaluated by two pediatric radiologists in a blinded manner for the mucosal pattern, presence of wall thickening, luminal distention of the small bowel, and extra-intestinal findings. Patient charts were reviewed to note clinical features and laboratory findings. The histopathologic review of the duodenal biopsies was re-conducted. Results: The mean duration of the disease was 5.6 ± 1.8 years (range: 3-7.2 years). In 24 (77%) of the patients, anti-endomysial antibody levels were elevated (mean 119.2 ± 66.6 RU/mL). Magnetic resonance enterography revealed normal fold pattern in all the patients. Ten (32%) patients had enlarged mesenteric lymph nodes. Conclusion: Although a majority of the patients had elevated anti-endomysial antibody levels indicating poor dietary compliance, magnetic resonance enterography did not show any mucosal abnormality associated with the inability of magnetic resonance enterography to detect mild/early changes of celiac disease in children. Therefore, it may not be useful for the follow-up of pediatric celiac disease.

Resumo Objetivo: Avaliar se a enterografia por ressonância magnética (ERM) consegue comprovar/mostrar a extensão da doença em pacientes pediátricos com doença celíaca (DC) comprovada por biópsia, comparar com um grupo de controle e correlacionar os achados da ERM com o nível de anticorpo antiendomísio (EMA) indicador de dieta sem glúten. Métodos: Foram recrutados 31 pacientes pediátricos (idade média entre 11,7 ± 3,1 anos) com DC comprovada por biópsia e 40 pacientes pediátricos em um grupo de controle. As imagens da ERM dos pacientes com DC e no grupo de controle foram avaliadas por dois radiologistas pediátricos às cegas para o padrão da mucosa, presença de espessamento da parede, dilatação luminal do intestino delgado e achados extraintestinais. Os prontuários dos pacientes foram revisados para anotação de características clínicas e achados laboratoriais. A avaliação histopatológica das biópsias duodenais foi feita novamente. Resultados: A duração média da doença foi 5,6 ± 1,8 anos (faixa de 3-7,2 anos). Em 24 (77%) dos pacientes, os níveis EMA estavam elevados (média 119,2 ± 66,6 RU/mL). A ERM revelou um padrão de pregas normal em todos os pacientes; 10 (32%) dos pacientes apresentaram gânglios linfáticos mesentéricos aumentados. Conclusão: Apesar de a maioria dos pacientes ter níveis elevados de EMA, o que indica uma dieta pobre, a ERM não mostrou anomalia na mucosa associada à incapacidade de a ERM detectar alterações leves/precoces de DC nas crianças. Portanto, ela pode não ser útil no acompanhamento da DC pediátrica.

Magnetic resonance enterography in pediatric celiac disease.

OBJECTIVE: To assess if magnetic resonance enterography is capable of showing evidence/extent of disease in pediatric patients with biopsy-proven celiac disease by comparing with a control group, and to correlate the magnetic resonance enterography findings with anti-endomysial antibody level, which is an indicator of gluten-free dietary compliance. METHODS: Thirty-one pediatric patients (mean age 11.7±3.1 years) with biopsy-proven celiac disease and 40 pediatric patients as a control group were recruited in the study. The magnetic resonance enterography images of both patients with celiac disease and those of the control group were evaluated by two pediatric radiologists in a blinded manner for the mucosal pattern, presence of wall thickening, luminal distention of the small bowel, and extra-intestinal findings. Patient charts were reviewed to note clinical features and laboratory findings. The histopathologic review of the duodenal biopsies was re-conducted. RESULTS: The mean duration of the disease was 5.6±1.8 years (range: 3-7.2 years). In 24 (77%) of the patients, anti-endomysial antibody levels were elevated (mean 119.2±66.6RU/mL). Magnetic resonance enterography revealed normal fold pattern in all the patients. Ten (32%) patients had enlarged mesenteric lymph nodes. CONCLUSION: Although a majority of the patients had elevated anti-endomysial antibody levels indicating poor dietary compliance, magnetic resonance enterography did not show any mucosal abnormality associated with the inability of magnetic resonance enterography to detect mild/early changes of celiac disease in children. Therefore, it may not be useful for the follow-up of pediatric celiac disease.

Neurological features and management of Wilson disease in children: an evaluation of 12 cases.

AIM: Wilson's disease is an autosomal recessive disorder of copper metabolism which leads to copper overload in different tissues of the body. The aim of this study was to present the neurologic features of Wilson's disease and to assess the clinical course of neurological findings in children receiving anti-copper treatment. MATERIAL AND METHODS: Twelve children with a diagnosis of Wilson's disease and findings of central nervous system involvement who were followed up in the Department of Pediatric Neurology and Pediatric Gastroenterology of the School of Medicine at Erciyes University were enrolled in the study. RESULTS: The study cases consisted of five boys (42%) and seven girls (58%). The mean age at the time of diagnosis was 9.9±3.4 years (5-15 years). The mean duration of follow-up was 49.0±36.4 months (15-128 months). Neurological findings at presentation included headache in seven cases (58%), tremor in seven cases (58%), dystonia in three cases (25%), ataxia in two cases (17%), dizziness in two cases (17%), numbness in the hands and acute weakness in one case (8%) and syncope in one case (8%). Headache, dizziness, syncope, numbness in hands and acute weakness symptoms resolved completely within six months after receiving treatment. Movement disorders either decreased or remained stable in seven of the eight cases. However, one patient developed progressively worsening dystonia despite to all treatments. CONCLUSIONS: Wilson's disease can be manifested with signs and symptoms of central nervous system in the childhood. Wilson's disease should be considered in all children presenting with movement disorders. A complete neurological assessment should be carried out in all cases with Wilson's disease.

Misdiagnosis of gastroesophageal reflux disease as epileptic seizures in children.

BACKGROUND: Gastroesophageal reflux disease (GERD) can mimic epileptic seizure, and may be misdiagnosed as epilepsy. On the other hand, GERD can be more commonly seen in children with neurological disorders such as cerebral palsy (CP); this co-incidence may complicate the management of patients by mimicking refractory seizures. OBJECTIVE: The purpose of our study was to evaluate the clinical features, definite diagnoses and treatment approaches of the patients with clinically suspected GERD who were referred to the division of pediatric neurology with a suspected diagnosis of epileptic seizure. We also aimed to investigate the occurrence of GERD in children with epilepsy and/or CP. METHODS: Fifty-seven children who had a final diagnosis of GERD but were initially suspected of having epileptic seizures were assessed prospectively. RESULTS: All patients were assigned to 3 groups according to definite diagnoses as follows: patients with only GERD who were misdiagnosed as having epileptic seizure (group 1: n=16; 28.1%), those with comorbidity of epilepsy and GERD (group 2: n=21; 36.8%), and those with the coexistence of GERD with epilepsy and CP (group 3: n=20; 35.1%). Five patients (8.8%) did not respond to anti-reflux treatment and laparoscopic reflux surgery was performed. The positive effect of GERD therapy on paroxysmal nonepileptic events was observed in 51/57 (89.5%) patients. CONCLUSIONS: GERD is one of the important causes of paroxysmal nonepileptic events. In addition, GERD must be kept in mind at the initial diagnosis and also in the long-term management of patients with neurological disorders such as epilepsy and CP.