Familial Mediterranean Fever Mutation Analysis in Pediatric Patients With Inflammatory Bowel Disease: A Multicenter Study.

BACKGROUND: The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously. METHODS: Children with IBD (334 ulcerative colitis (UC), 224 Crohn's disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined. RESULTS: A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/ heterozygous) in patients with UC (P < .05). There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007). CONCLUSION: Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.

Left ventricular mechanics are affected in children with celiac disease: A study based on two-dimensional speckle tracking echocardiography.

BACKGROUND: An association between cardiomyopathy and celiac disease has been reported, but not frequently. We examined the effects on cardiac mechanics in children with celiac disease (CD) by two-dimensional speckle tracking echocardiography (2DSTE). METHODS: Eighty-one children with CD were compared with a control group comprising 51 healthy children by echocardiographic examination. Children with CD who had been on gluten-free diet for more than 6 months were divided into two different groups: group 1 was positive for serum antitissue transglutaminase antibody (n=48), and group 2 was negative for serum antitissue transglutaminase antibody (n=33). Cardiac functions were evaluated in all children using conventional echocardiography, tissue Doppler imaging (TDI), and 2DSTE methods. RESULTS: For children with CD, the mean age and male:female ratio were 10.1±4.0 years and 26/55 (67% female), respectively, which did not differ from the controls. Patients were diagnosed at a mean age of 7.9±4.1 years, and the mean follow-up time was 2.37±2.98 years. Conventional echocardiography and TDI measurements did not differ between groups. The left ventricular longitudinal and radial strains, and strain rate values were significantly lower in patients with CD, particularly in those with positive antitissue transglutaminase antibody compared with the control group. CONCLUSIONS: Our results suggest that 2DSTE is superior to conventional and TDI echocardiography for evaluating subclinical carditis in children with CD.

Investigation of cardiomyopathy in children with cirrhotic and noncirrhotic portal hypertension.

BACKGROUND: Cirrhotic cardiomyopathy (CCMP) is a functional disorder characterized by electrophysiological disturbances, and diastolic and/or systolic dysfunction in patients with liver disease. This disorder is a well-defined entity in adults, but pediatric data are limited. The aim of the study was to determine the incidence, features, and risk factors of CCMP in children with portal hypertension (PHT). METHODS: This study included 50 children with cirrhotic PHT (40/50) and noncirrhotic PHT (10/50). Fifty healthy children were also selected for the control group. Electrocardiography and echocardiography were used to evaluate cardiac functions. Corrected QT (QTc) ≥ 0.45 was accepted as prolonged on electrocardiography. The study group was divided into 3 groups: cirrhotic, noncirrhotic, and control. Then, the CCMP group was created according to the diagnostic criteria. Latent CCMP was diagnosed in the presence of prolonged-QTc along with a minor criterion (tachycardia). Manifest CCMP was diagnosed in the presence of at least 2 major criteria (prolonged-QTc along with abnormal echocardiographic findings). Moreover, in this study, the risk factors for CCMP were investigated. RESULTS: The CCMP group included 10 cases (20%). Nine of these cases had latent CCMP (18%), and the remaining one (2%) had manifest CCMP. All of the cases with CCMP had cirrhosis and ascites. None of the patients with CCMP had severe cardiac symptoms, but they were already using some cardioprotective drugs such as propanolol and spironolactone. As risk factors for CCMP, pediatric end-stage liver disease scores, Child-Pugh scores, and ascites grades were found to be significant for the determination of CCMP. The most important risk factor was ascites severity (P = 0.001, odds ratio 9.4). CONCLUSIONS: Approximately 20% of children with PHT have CCMP. A detailed cardiac examination should be carried out periodically in children with cirrhotic PHT, especially in the presence of ascites and high Child-Pugh score.

Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort.

BACKGROUND & AIMS: Proprotein convertase 1/3 (PC1/3) deficiency, an autosomal-recessive disorder caused by rare mutations in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene, has been associated with obesity, severe malabsorptive diarrhea, and certain endocrine abnormalities. Common variants in PCSK1 also have been associated with obesity in heterozygotes in several population-based studies. PC1/3 is an endoprotease that processes many prohormones expressed in endocrine and neuronal cells. We investigated clinical and molecular features of PC1/3 deficiency. METHODS: We studied the clinical features of 13 children with PC1/3 deficiency and performed sequence analysis of PCSK1. We measured enzymatic activity of recombinant PC1/3 proteins. RESULTS: We identified a pattern of endocrinopathies that develop in an age-dependent manner. Eight of the mutations had severe biochemical consequences in vitro. Neonates had severe malabsorptive diarrhea and failure to thrive, required prolonged parenteral nutrition support, and had high mortality. Additional endocrine abnormalities developed as the disease progressed, including diabetes insipidus, growth hormone deficiency, primary hypogonadism, adrenal insufficiency, and hypothyroidism. We identified growth hormone deficiency, central diabetes insipidus, and male hypogonadism as new features of PCSK1 insufficiency. Interestingly, despite early growth abnormalities, moderate obesity, associated with severe polyphagia, generally appears. CONCLUSIONS: In a study of 13 children with PC1/3 deficiency caused by disruption of PCSK1, failure of enteroendocrine cells to produce functional hormones resulted in generalized malabsorption. These findings indicate that PC1/3 is involved in the processing of one or more enteric hormones that are required for nutrient absorption.

Assessment of living donors with respect to pre- and posttransplant psychosocial properties and posttransplant family functioning in pediatric liver transplantation.

BACKGROUND/AIMS: We aimed in this study to investigate pre- and posttransplant clinical and psychosocial features of the donors and the effects of living-related liver transplantation and possible relevant factors on psychosocial outcome and family functioning. METHODS: Thirty-two living donors (19 females, age 31.84 ± 7.10 years) were evaluated. Medical records of donors regarding pre- and posttransplant clinical and psychological features and family life were evaluated. RESULTS: The donors were parents (n=28, 87.6%) in most. In the pretransplant evaluation, 5 donors (19.3%) had anxiety regarding postoperative complications and quality of life. Donors were discharged from the hospital in a median of 7 days (range, 5-30 days). Return to work and feeling of complete well-being were accomplished in a median of 4 weeks (range, 1-32 weeks) and 10 weeks (range, 4-48 weeks), respectively. Sixteen recipients (50.0%) suffered from major complications, and 3 (9.4%) required invasive intervention. Fourteen donors (43.4%) reported pain around the surgical incision and nonspecific gastrointestinal problems postoperatively. Psychological problems were observed in 8 donors (25.0%); 2 (6.3%) had depression requiring drug and psychotherapeutic intervention. Psychological disruption was found to be correlated with the presence of problems in the recipient (p<0.01, r=0.487). The donors' relationship with the recipient was negatively affected in 1 (3.1%), but improved in 15 (46.9%) cases. Nine donors (34.6%) displayed nervous behavior toward their spouses, and 2 (7.7%) later divorced. Life of the other family members was negatively affected in 8 (30.7%). Two donors' spouses (7.7%) failed to carry out domestic responsibilities. CONCLUSIONS: Psychological disturbance and abnormal family functioning are frequently observed during the posttransplant period. Therefore, psychologic assessment and evaluation of family functioning should be regularly repeated during the posttransplant period.

Portal gastropathy and duodenopathy in children with extrahepatic and intrahepatic portal hypertension: endoscopic diagnosis and histologic scoring.

OBJECTIVES: The aim of the study was to determine the frequency of portal gastropathy (PG) and duodenopathy (PD) in children, to document the correlation of various clinical and laboratory parameters associated with portal hypertensive gastroduodenal lesions, to compare the endoscopic portal hypertensive lesions with different histologic findings, and to evaluate the use of a possible histologic scoring system. METHODS: All children undergoing endoscopic investigation for portal hypertension (PH) between January 2006 and November 2007 were analysed retrospectively. Clinical and demographical data and endoscopic and histologic findings were recorded. Histologic findings suggestive of PG and PD (capillary dilation, increased numbers of capillaries, histologic bleeding, and edema) were scored. RESULTS: Of 51 consecutive children (29 boys, mean age 10.1 ± 3.6 years [range 2.5-15.8 years]), 28 were cirrhotic. PG was diagnosed in 58.8% endoscopically. Children with cirrhotic PH had the highest rate of PG (64.3%), whereas those with extrahepatic or intrahepatic noncirrhotic PH were alike (50% and 54.5%, respectively). Baveno PG scores were higher in children with cirrhosis with higher Child-Pugh scores. Capillary dilation was the only histologic finding showing significant association with the endoscopic diagnosis. Only 9% had PD on endoscopy. None of the histologic findings correlated with endoscopic diagnosis of PD. CONCLUSIONS: PG and PD are seen in children with extrahepatic and intrahepatic PH at rates similar to those reported in adult studies. Baveno PG scores increased in parallel with Child-Pugh class in children with cirrhosis. Capillary dilation was the only histologic finding showing significant association with the endoscopic diagnosis of PG in this study.

Human herpes virus type 8-associated Kaposi sarcoma in a pediatric liver transplant recipient.

Development of KS in pediatric liver transplant recipients is a rare entity and has dismal prognosis. Latent HHV-8 infection, immunosuppression, and genetic predisposition are possible etiological factors. Decreasing the dose or cessation of immunosuppressive drugs, switching to sirolimus with antiproliferative and antitumor properties, and different chemotherapeutic regimens are the current therapeutic strategies. We herein report a pediatric liver transplant recipient who developed generalized KS at post-transplant fifth month. The disease had an aggressive course despite the highly toxic chemotherapy. On the other hand, a prompt and durable response was provided by paclitaxel with tolerable side effects. The patient is now free of disease for at least 24 months and healthy with good graft function under sirolimus therapy as maintenance immunosuppression. Instead of highly toxic chemotherapy, paclitaxel can be used as therapeutic option in cases with generalized disease and in those who are unresponsive to conventional chemotherapy. However, new studies are needed to assess the efficacy of the paclitaxel therapy in KS in the liver transplant recipients.

Childhood non-Hodgkin's lymphoma arising as a complication early in the course of Crohn's disease.

The neoplastic change in patients with Crohn's disease is usually seen in the form of adenocarcinoma. Primary gastrointestinal lymphoma complicating chronic inflammatory bowel diseases is thought to be uncommon. This report describes a case of gastrointestinal lymphoma in a 12-year-old boy with Crohn's disease of one-year duration that initially manifested as an abdominal mass. Although Crohn's disease may present as a palpable abdominal mass, changing symptomatology should always warrant consideration of developing lymphoma complicating inflammatory bowel diseases. It is our hope that this case report gives the clinician an insight into the possibility of lymphoma development, even in the early course of the disease, and stresses the importance of obtaining a reliable histological diagnosis whenever possible.

The role of the non-invasive serum marker FibroTest-ActiTest in the prediction of histological stage of fibrosis and activity in children with naïve chronic hepatitis B infection.

The aim of this study was to investigate whether the non-invasive serum marker FibroTest-ActiTest (FT-AT) reliably predicts the histological stage of fibrosis and/or activity, and decreases the need for a liver biopsy. Twenty-five children with naïve chronic hepatitis B were analyzed for haptoglobin, alpha2-macroglobulin, apolipoprotein A1, bilirubin, gamma-glutamyl transferase, and alanine aminotransferase activity, and the FT-AT scores were computed. FT-AT scores were compared with histological data. FT predicted insignificant fibrosis in 14/23 (61%) patients at a cut-off level of 0.31. Nine patients (36%) had significant histological fibrosis, but none were predicted by FT. There was no correlation between FT scores and histological stage of fibrosis (r: -0.221, p = 0.228). All 4 patients with significant histological activity had corresponding significant activity in AT (100%). Fifteen out of the 19 patients (78.9%) with significant activity in AT had insignificant histological activity. At the cut-off level of 0.36, AT predicted insignificant activity in all 6 patients (100%). There was no correlation between AT scores and histological activity (r: 0.245, p = 0.237). According to histological data, 12 patients were candidates for treatment, but FT-AT did not predict 3 of them (25%). FT-AT does not appear ready for use in detecting either the stage of fibrosis or activity in children with chronic hepatitis B.

Valproic acid-associated vanishing bile duct syndrome.

Hepatotoxicity as a result of valproic acid therapy is well documented. Elevation in aminotransferase activities is rarely associated with symptoms. It sometimes manifests as acute liver failure. Here, we report a 8-year-old girl who was referred for unresolving jaundice and itching for 3 months. Past history revealed afebrile convulsion 5 months previously and beginning of valproic acid treatment. Valproic acid was discontinued after the development of jaundice. Physical examination revealed ichterus, xanthomas on extensor surfaces of extremities, and hepatomegaly without any sign of chronic liver disease. Total and direct bilirubin levels were 20.2 and 12.9 mg/dL, respectively. Enzyme activities indicating cholestasis were increased together with blood cholesterol. Tests for infectious and autoimmune, metabolic, and genetic disorders were not informative. Liver biopsy revealed portal inflammation, severe bile duct loss, and cholestasis. The patient was considered to have valproic acid-associated vanishing bile duct syndrome, which has not been reported previously.

Hepatic adenomatosis in a 7-year-old child treated earlier with a Fontan procedure.

Patients who undergo a Fontan procedure experience some degree of liver disease. Hemodynamic changes such as central venous hypertension, depressed dynamic cardiac output, and late ventricular dysfunction combined with long-standing hypoxia preceding the Fontan procedure all are recognized risk factors for hepatic injury. The histopathologic changes associated with cardiac hepatopathy include chronic passive congestion, centrilobular necrosis, and cardiac cirrhosis. However, hepatic adenoma and hepatic adenomatosis (HA) are not well-known pathologies during the course of cardiac hepatopathy. This study focused on a 7-year-old girl with chronic hepatic changes and HA who had undergone a Fontan procedure. Hepatic adenomatosis was diagnosed on the basis of magnetic resonance imaging (MRI) and MRI-guided liver biopsy. To the best of the authors' knowledge, this case involved the youngest patient with hepatocellular adenomatosis documented in the literature. It was a unique case because the patient experienced HA after a Fontan procedure.

A case report: gastric adenocarcinoma in childhood.

Primary gastric adenocarcinoma is extremely rare in children, and accounts for 0.05% of all gastrointestinal malignancies during childhood. The initial symptoms of epigastric pain, feeling of fullness, belching, and loss of appetite are non-specific and misleading. Nausea, vomiting and weight loss may accompany, which also complicate reaching a prompt diagnosis. In the presented case, a 15-year-old girl admitted with ascites, pleural effusion, right supra-clavicular lymphadenopathy, and back pain. No primary focus of a malignancy was accomplished in radiological evaluation, and the diagnosis of gastric carcinoma was achieved with upper gastrointestinal system endoscopy. We point out the importance of upper gastrointestinal system endoscopy in patients with ascites and uncertain diagnosis of the primary focus of malignancy.

Investigation of impaired carbohydrate metabolism in pediatric liver transplant recipients.

OGTT was performed in 28 liver transplants maintained with tacrolimus to investigate carbohydrate metabolism and assess risk factors for development of PTDM. None had PTDM that was detected by OGTT. Early PTDM in four cases (14.3%) resolved in follow-up. Five new cases (17.9%) demonstrated DCM (DCM = IGT +/- hyperinsulinemia). Fasting measurements were normal in two hyperinsulinemic cases. With one (20%, p > 0.05) exception none of the children with DCM were overweight or had a family history of diabetes. All five (100%) children with DCM had been given high cumulative dosage of steroids 18 (78.3%)--without DCM (p > 0.05). The median age of children with DCM was greater [4.3 (12.7-18.0) vs. 7.0 (2.3-18.0) yr, p < 0.01] and duration of follow-up longer [5.3 (2.3-7.0) vs. 2.5 (0.7-7.3) yr, p < 0.05]. Four children (80%) with DCM were pubertal (p < 0.05). However, neither age nor duration of follow-up or pubertal stage had significant effect on DCM development. Early PTDM is a transient phenomenon and is not predictive for future development of diabetes. DCM is frequently observed in liver transplanted children. Albeit the children with DCM were given high cumulative dose of steroids, were older, mostly were pubertal, and had longer duration of follow-up, we cannot draw firm conclusions on effects of the risk factors on carbohydrate metabolism because of the small sample size and relatively short duration of follow-up. Unlike fasting measurements, OGTT can detect all children with DCM.

Intrapleural streptokinase treatment in children with empyema.

Our aim was to compare intrapleural streptokinase (SK) treatment and simple tube drainage in the treatment of children with complicated parapneumonic pleural effusion. A retrospective review of medical records included patient demographics, clinical presentation, biochemical and microbial studies of pleural effusion, radiographic evaluation of chest tube drainage, use of fibrinolytic agents and type of surgical intervention. During the 2.5-year period (1999-2002), 53 children (29 M, 24 F) with complicated parapneumonic effusions or empyema were identified. Closed tube drainage and antibiotic treatment were administered to patients with a diagnosis of complicated parapneumonic effusion (n = 24) until October 2000; after that time point, intrapleural streptokinase was added to this regimen (n = 29). The median age at the time of presentation was 2.5 years (range: 5 months-14.6 years). There were no significant differences in terms of clinical outcomes between the two groups. The average length of hospital stay was 19.1 +/- 5.5 and 21.9 +/- 11.2 days for the drainage and streptokinase groups, respectively; the time to afebrile state after admission was 5.8 +/- 4.1 and 7.6 +/- 7.5 days. The percentage of patients who eventually required surgical intervention was 8.3% for the drainage group and 20.6% for the streptokinase group. In conclusion, in the treatment of complicated parapneumonic effusions or empyema, the adjunctive treatment with intrapleural SK does not significantly reduce durations of fever, chest tube drainage and hospital stay, and the need for surgery, regardless of the stage of the disease, compared to simple closed tube drainage.

Transient peripheral leukocytosis in children with afebrile seizures.

The purpose of this study was (1) to demonstrate whether peripheral blood leukocytosis accompanies first afebrile seizures without bacterial infection, (2) to investigate the duration of leukocytosis, and (3) to assess the relationship between peripheral blood leukocytosis and seizure characteristics. Complete blood count was routinely obtained from all the patients. Blood and urine cultures were obtained from patients with leukocytosis. On the 24th hour of admission, a second complete blood count was obtained from patients with initial leukocytosis. Sixty-two children aged 4.0 +/- 3.6 years (range, 6 months-13 years)-31 boys (50%) and 31 girls (50%)--enrolled in the study. The findings showed that peripheral blood leukocytosis was found in 8% of afebrile children without status epilepticus and 41.6% of afebrile children with status epilepticus. An interesting finding of the study was that peripheral blood leukocytosis accompanied by afebrile seizures subsided in 24 hours. Transient leukocytosis could be found in children with afebrile seizures without bacterial infection.

The prevalence of anemia in adolescents: a study from Turkey.

A cross-sectional method was used to study a group of 400 high school students in Kocaeli, Turkey, aged 14 to 16 years, identified among 17,812 high school students. Students from 10 high schools were selected using a random sampling method. Whole blood counts were performed as a screening test for anemia. Serum ferritin levels and, when necessary, hemoglobin electrophoresis were determined for anemic students. Iron medication was prescribed for iron deficiency and genetic counseling was given to adolescents with thalassemia trait. Out of 338 participating students (mean age, 14.72+/-0.71 y), anemia (hemoglobin <12 g/dL for girls and <13 g/dL for boys) was detected in 17/174 girls (9.7%) and 6/164 boys (3.6%). Iron deficiency anemia was detected in 20/23 (86.9%) of anemic children [15/17 (88.2%) girls and 4/6 (66.6%) boys]. Of 23 students with anemia 2 had beta-thalassemia trait and 2 had both iron deficiency, and beta-thalassemia trait. Etiology of anemia could not be defined in 1 student. The prevalence of adolescent anemia in Kocaeli is almost equal to that in developed countries.

Peritoneal tuberculosis with elevated serum CA 125 level mimicking advanced ovarian carcinoma in an adolescent.

Differential diagnosis between tuberculous peritonitis and peritonitis carcinomatosis is extremely difficult in patients with ascites, peritoneal implants and elevated CA 125 level. A 16-year-old girl presented with abdominal distention, intermittent fever and weight loss. Physical examination and radiologic studies revealed massive ascites, generalized peritoneal thickening and slightly enlarged right ovary with a cystic mass and left pleural effusion. Serum CA 125 was 939 U/L (normal range: 0-35 U/L) and other tumor markers including alpha fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) were within normal range. Acid-fast stain and culture were negative for Mycobacterium tuberculosis. Diagnostic laparoscopy and biopsy were performed with the presumptive diagnosis of peritonitis carcinomatosis, and histologic examination revealed multiple granulomas with epithelioid cells and caseification necrosis which confirmed tuberculosis. Quadruple anti-tuberculosis treatment was administered and the patient's clinical findings and serum CA 125 level returned to normal. In conclusion, tuberculous peritonitis should be considered in the differential diagnosis of patients with ascites and elevated serum CA 125. This marker may be useful in monitoring treatment response.