Clinical features of generalized lipodystrophy in Turkey: A cohort analysis.

AIM: To describe the Turkish generalized lipodystrophy (GL) cohort with the frequency of each complication and the death rate during the period of the follow-up. METHODS: This study reports on 72 patients with GL (47 families) registered at different centres in Turkey that cover all regions of the country. The mean ± SD follow-up was 86 ± 78 months. RESULTS: The Kaplan-Meier estimate of the median time to diagnosis of diabetes and/or prediabetes was 16 years. Hyperglycaemia was not controlled in 37 of 45 patients (82.2%) with diabetes. Hypertriglyceridaemia developed in 65 patients (90.3%). The Kaplan-Meier estimate of the median time to diagnosis of hypertriglyceridaemia was 14 years. Hypertriglyceridaemia was severe (≥ 500 mg/dl) in 38 patients (52.8%). Seven (9.7%) patients suffered from pancreatitis. The Kaplan-Meier estimate of the median time to diagnosis of hepatic steatosis was 15 years. Liver disease progressed to cirrhosis in nine patients (12.5%). Liver disease was more severe in congenital lipodystrophy type 2 (CGL2). Proteinuric chronic kidney disease (CKD) developed in 32 patients (44.4%) and cardiac disease in 23 patients (31.9%). Kaplan-Meier estimates of the median time to diagnosis of CKD and cardiac disease were 25 and 45 years, respectively. Females appeared to have a more severe metabolic disease, with an earlier onset of metabolic abnormalities. Ten patients died during the follow-up period. Causes of death were end-stage renal disease, sepsis (because of recurrent intestinal perforations, coronavirus disease, diabetic foot infection and following coronary artery bypass graft surgery), myocardial infarction, heart failure because of dilated cardiomyopathy, stroke, liver complications and angiosarcoma. CONCLUSIONS: Standard treatment approaches have only a limited impact and do not prevent the development of severe metabolic abnormalities and early onset of organ complications in GL.

Pediatric EBV Positive Mucocutaneous Ulceration in Stomach a Rare Entity.

Epstein Barr virus (EBV) related lymphoproliferative diseases may occur in immunocompromised patients or patients with a history of drug use causing immunodeficiency. EBV positive mucocutaneous ulceration in the new classification of lymphoproliferative diseases in 2016 is very rare in children. Involvement occurs in the skin, oral mucosa, and gastrointestinal system. Gastric involvement is very rare in the literature. There is no case of gastric involvement in children. There are no specified modalities in the treatment of EBV positive mucocutaneous ulceration. We presented our pediatric patient with ataxia telangiectasia who presented with abdominal pain and difficulty swallowing and diagnosed with EBV positive mucocutaneous ulceration in the stomach. We started brentuximab vedotin during the treatment process, and complete remission was achieved after 6 cures of treatment. Our patient is the first case of EBV positive mucocutaneous ulceration in the pediatric case series.

Biallelic CAV1 null variants induce congenital generalized lipodystrophy with achalasia.

OBJECTIVE: CAV1 encodes caveolin-1, a major protein of plasma membrane microdomains called caveolae, involved in several signaling pathways. Caveolin-1 is also located at the adipocyte lipid droplet. Heterozygous pathogenic variants of CAV1 induce rare heterogeneous disorders including pulmonary arterial hypertension and neonatal progeroid syndrome. Only one patient was previously reported with a CAV1 homozygous pathogenic variant, associated with congenital generalized lipodystrophy (CGL3). We aimed to further delineate genetic transmission, clinical, metabolic, and cellular characteristics of CGL3. DESIGN/METHODS: In a large consanguineous kindred referred for CGL, we performed next-generation sequencing, as well as clinical, imagery, and metabolic investigations. We studied skin fibroblasts from the index case and the previously reported patient with CGL3. RESULTS: Four patients, aged 8 months to 18 years, carried a new homozygous p.(His79Glnfs*3) CAV1 variant. They all displayed generalized lipodystrophy since infancy, insulin resistance, low HDL-cholesterol, and/or high triglycerides, but no pulmonary hypertension. Two patients also presented at the age of 15 and 18 years with dysphagia due to achalasia, and one patient had retinitis pigmentosa. Heterozygous parents and relatives (n = 9) were asymptomatic, without any metabolic abnormality. Patients' fibroblasts showed a complete loss of caveolae and no protein expression of caveolin-1 and its caveolin-2 and cavin-1 partners. Patients' fibroblasts also displayed insulin resistance, increased oxidative stress, and premature senescence. CONCLUSIONS: The CAV1 null variant investigated herein leads to an autosomal recessive congenital lipodystrophy syndrome. Loss of caveolin-1 and/or caveolae induces specific manifestations including achalasia which requires specific management. Overlapping phenotypic traits between the different CAV1-related diseases require further studies.

Liver Cirrhosis in a Patient with Crigler Najjar Syndrome.

INTRODUCTION: Crigler Najjar (CN) disease is a genetic disorder which results in increased unconjugated bilirubin level. Liver parenchyma was previously considered structurally normal. Recent reports describe significant fibrosis in the liver parenchyma of patients with CN syndrome. CASE REPORT: We present a patient with persistent unconjugated hyperbilirubinemia, clinically diagnosed as CN-2, with a UGT1 A1 p. H39D (c.115C > G) (His → Asp) mutation. She required hepatic transplantation at the age of 17.5 years for biliary cirrhosis. Explanted liver histopathology revealed regenerative cirrhotic nodules with dilated bile ducts filled with bile plugs. CONCLUSION: CN can develop significant hepatic fibrosis/cirrhosis requiring liver transplantation.

Investigation of toggling effect on pullout performance of pedicle screws.

Objective of this study is to assess the pullout performance of various pedicle screws in different test materials after toggling tests comparatively. Solid core, cannulated (cemented), novel expandable and solid-core (cemented) pedicle screws were instrumented to the polyurethane foams (Grade 10 and Grade 40) produced in laboratory and bovine vertebra. ASTM F543 standard was used for preparation process of samples. Toggling tests were carried out. After toggling test procedures, pullout tests were performed. Load versus displacement graph was recorded, and the ultimate pullout force was defined as the maximum load (pullout strength) sustained before failure of screw. Anteriosuperior and oblique radiographs were taken from each sample after instrumentation in order to examine screw placement and cement distribution. The pullout strength of pedicle screws decreased after toggling tests with respect to the initial condition. While the cemented solid-core pedicle screws had the highest pullout strength in all test materials, they had the highest strength differences. The cemented solid-core pedicle screws had decrement rates of 27% and 16% in Grade 10 and Grade 40, respectively. There are almost same decrement rate (between 5.5% and 6.5%) for all types of pedicle screws instrumented to the samples of bovine vertebra. The pullout strengths of novel expandable pedicle screws in both of early period and after toggling conditions were almost similar, in other words, the decrement rates of it were lower than other types. According to the data collected from this study, polymethylmethacrylate augmentation significantly decreases pullout strength following the toggling loads. Higher brittleness of cured polymethylmethacrylate has adverse effect on the pullout strength. Although augmentation is an important process for enhancing pullout strength in early period, it has some disadvantages for preserving stabilization in a long time. Expandable pedicle screw with polyetheretherketone shell may be good alternative to polymethylmethacrylate augmentation on both primer stabilization and long-term loading application with toggling.

Pullout performance comparison of novel expandable pedicle screw with expandable poly-ether-ether-ketone shells and cement-augmented pedicle screws.

Aim of this study is to assess the pullout performance of various pedicle screws in different test materials. Polyurethane foams (Grade 10 and Grade 40) produced in laboratory and bovine vertebrae were instrumented with normal, cannulated (cemented), novel expandable and normal (cemented) pedicle screws. Test samples were prepared according to the ASTM F543 standard testing protocols and surgical guidelines. To examine the screw placement and cement distribution, anteriosuperior and oblique radiographs were taken from each sample after insertion process was completed. Pullout tests were performed in an Instron 3369 testing device. Load versus displacement graphs were recorded and the ultimate pullout force was defined as the maximum load (pullout strength) sustained before failure of screw. Student's t-test was performed on each group whether the differences between pullout strength of pedicle screws were significant or not. While normal pedicle screws have the lowest pullout strength in all test materials, normal pedicle screws cemented with polymethylmethacrylate exhibit significantly higher pullout performance than others. For all test materials, there is a significant improvement in pullout strength of normal screws by augmentation. While novel expandable pedicle screws with expandable poly-ether-ether-ketone shells exhibited lower pullout performance than normal screws cemented with polymethylmethacrylate, their pullout performances in all groups were higher than the ones of normal and cannulated pedicle screws. For all test materials, although cannulated pedicle screws exhibit higher pullout strength than normal pedicle screws, there are no significant differences between the two groups. The novel expandable pedicle screws with expandable poly-ether-ether-ketone shells may be used instead of normal and cannulated pedicle screws cemented with polymethylmethacrylate due to their good performances.

Acute liver failure in children: 20-year experience.

BACKGROUND/AIMS: We aimed to determine the causes, demographic findings, clinical status, outcomes, and prognostic risk factors of patients with acute liver failure admitted to Hacettepe University Children's Hospital between October 1987-October 2006. METHODS: This retrospective case study included 74 patients with acute liver failure according to the Pediatric Acute Liver Failure Study Group definition. RESULTS: The etiology of acute liver failure was metabolic in 26 (35.1%) and infectious in 21 (28.4%) patients. Sixteen (21.6%) patients had indeterminate causes. Wilson's disease (16/26 patients, 61.5%) was the most frequent metabolic disease, while hepatitis A (14/21 patients, 66.7%) was the most frequent infectious agent. Neurologic functions were normal in 21 (28.4%) patients. Forty-nine (66.2%) patients died and 24 (32.4%) recovered. Two patients underwent liver transplantation. The mortality rate was 82.9% for patients who were not transplanted but fulfilled King's College Hospital criteria and 45.4% for patients who were not suitable for transplantation. This difference was statistically significant (p=0.001). Total bilirubin >5.35 mg/dl, international normalized ratio (INR) >3.66 and prothrombin time >23.5 seconds were shown to be the risk factors to predict death. CONCLUSIONS: Metabolic and infectious etiologies were responsible for most of the acute liver failure cases. Clinical encephalopathy may not be present in children.

Wiedemann-Rautenstrauch syndrome: report of a variant case.

Wiedemann-Rautenstrauch syndrome (WRS) is a rare autosomal recessive disorder that includes premature aging phenotype at birth. The condition is also known as a neonatal progeroid syndrome. Up to now only a few published case reports have been documented. The syndrome is characterized by progeroid appearance, decreased subcutaneous fat, hypotrichosis, macrocephaly, and in some natal teeth. We describe a new patient with features of bilaterally pelvicalyceal ectasia and partial syndactyly on 2th and 3th toes, not previously described, to our knowledge.

Ineffectiveness of infliximab therapy in severe infantile Crohn's disease.

Crohn's disease is extremely rare in infancy and can be present in severe forms. Infants with Crohn's disease might require intensive immunosuppressive therapy. Infliximab is a chimeric mouse/human monoclonal IgG1 antibody against tumor necrosis factor-α, and completely neutralizes its biologic activity. Though widely used in the treatment of pediatric Crohn's disease, there are few data regarding its applicability in infancy. We therefore report herein our experiences with infliximab therapy in two infantile patients with Crohn's disease who were resistant to conventional therapies; one patient showed a partial response while there was no response in the second. We were unable to achieve satisfactory results from infliximab therapy. It remains to be determined whether inflammatory bowel disease starting in infancy represents a separate pathogenetic subgroup and whether the inflammatory bowel disease diagnosis should follow the exclusion of an immunodeficiency state. Studies in larger series are needed to further clarify the efficacy, safety and timing of infliximab therapy for infantile Crohn's disease patients.

The presentation of celiac disease in 220 Turkish children.

The aim of this study was to investigate the presentation pattern of newly diagnosed celiac disease (CD) in Turkish children in the last eight years. Two hundred twenty patients with newly diagnosed CD were included. The medical records of all the patients between January 2000 and October 2008 were reviewed. The clinical spectrum was divided into three categories according to the main symptoms that led to the diagnosis: gastrointestinal presentation, non-gastrointestinal presentation, and silent cases. The mean age of the patients was 7.2 +/- 4.3 years at diagnosis. According to the presenting signs, the patients were defined as gastrointestinal presentation (129 patients, 58.6%), non-gastrointestinal presentation (76 patients, 34.6%) and silent cases (15 patients, 6.8%). This study showed that the number/percentage of CD cases who presented with non-gastrointestinal symptoms/conditions, so-called "non-gastrointestinal presentation", have been increasing in the last eight years.

The association of inflammatory bowel disease and Mediterranean fever gene (MEFV) mutations in Turkish children.

BACKGROUND AND AIMS: Familial Mediterranean fever (FMF) and inflammatory bowel disease (IBD) concordance has been investigated in a few studies. We investigated MEFV mutations and prevalence of FMF disease in Turkish children with IBD and their relationship with the disease severity. METHODS: Sixteen patients with ulcerative colitis (UC), 14 with Crohn's disease (CD) and three with indeterminate colitis (IC) were enrolled in the study (median age 13 years, range 0.6-16 years, n = 19 boys). Demographic, clinical and laboratory characteristics of the patients were evaluated as well as the parameters of disease severity. All patients were screened for 12 common MEFV mutations. RESULTS: MEFV mutations were detected in 17 of 66 (25.7%) alleles. Seven patients (four patients with CD, two with IC, and one with UC) were also diagnosed as FMF. FMF disease was found in seven of all IBD patients (21.2%) and four of them had CD. M694V was the leading mutation, and as a disease-causing mutation, it was found to be significantly more frequent in CD patients than UC patients (Fisher's exact test P = 0.03). Demographics, laboratory evaluations, growth parameters, extraintestinal manifestations, and treatment with immunosuppressive agents other than steroids were comparable between the patients with and without FMF in most aspects. CONCLUSIONS: Although this is a small cohort, disease-causing MEFV mutations and FMF disease rate were increased among our patients with IBD. The increase was prominent among CD patients, whereas in UC the rate was similar to the Turkish healthy control population.

Detection of TT virus (TTV) by three frequently-used PCR methods targeting different regions of viral genome in children with cryptogenic hepatitis, chronic B hepatitis and hbs carriers.

This study was designed so that three sensitive and widely-used polymerase chain reaction (PCR) methods for the detection of TT virus or Torque Teno virus (TTV) would be simultaneously applied to a large number of subjects to evaluate performances of the various PCR protocols with different genotype sensitivities. Sera were collected from 92 children admitted to Hacettepe University Ihsan Dogramaci Children's Hospital Pediatric Gastroenterology Unit (17 cryptogenic chronic hepatitis, 17 asymptomatic HBs carriers, 18 chronic HBV patients and 40 healthy children). TTV DNA was detected via nested N22, nested 3'-UTR and 5'-UTR PCRs for all samples. Differences in TTV D N A detection prevalences were n o t statistically significantbetween the study groups with all TTV DNA and liver enzyme levels. A significant agreement between PCR methods that target UTR was observed. TTV detection rate increased with age, suggesting a non-parenteral, environmental exposure to the virus for the study population.

Comparison of short- and long-term treatment protocols and the results of second-line quadruple therapy in children with Helicobacter pylori infection.

BACKGROUND: Research regarding the optimal therapeutic approach to Helicobacter pylori infection in children is ongoing. There is no consensus as to duration of treatment or second-line therapy. The purpose of this study was compare the efficacy of 7-day and 14-day triple therapies and report the results of second-line quadruple therapy in children. METHODS: A total of 275 consecutive H. pylori-infected patients were enrolled into two groups. Group 1 (n = 180) received triple therapy with 14 days of amoxicillin and clarithromycin and 21 days of proton pump inhibitor. Group 2 (n = 95) received triple therapy including 7 days of amoxicillin and clarithromycin with 21 days of proton pump inhibitor. Subsequently, 89 patients not responding to the triple therapies received quadruple therapy comprising omeprazole (14 days), bismuth subcitrate (7 days), doxycycline (7 days), and metronidazole (7 days). Eradication was evaluated by 13C-urea breath test. RESULTS: The per-protocol eradication rates in groups 1 and 2 were 60.5% and 55.8%, respectively (P = 0.44). In the second interview with 227 patients, severe symptoms were reported to have disappeared in 59% and decreased notably in 34.8%. Helicobacter pylori was eradicated in 66.7% of patients at the end of the quadruple therapy. In the third interview with 75 patients, severe symptoms had decreased in 38.6% and disappeared in 56%. CONCLUSIONS: The different duration of the two treatment regimens had no impact on eradication rates. Furthermore, quadruple therapy was necessary to achieve H. pylori eradication after triple therapy. However, the eradication rate with quadruple therapy was still insufficient. Consequently, a new therapeutic approach to H. pylori infection in children is needed.

Bone mineralization in children with inflammatory bowel disease: what is the role of zinc?

BACKGROUND/AIMS: Bone demineralization is a significant problem in pediatric inflammatory bowel disease. Contributing factors include inadequate nutrition, corticosteroid therapy and decreased physical activity. Although zinc is needed for osteoblastic activity and collagen synthesis, its role in bone development is uncertain. The aim of this study was to investigate the relation between the serum zinc level and bone mineral indexes of 28 children with inflammatory bowel disease. METHODS: Bone mineral content and bone mineral density at lumbar 1-4 vertebrae were measured by dual energy X-ray absorptiometry in all patients and 56 controls. Serum zinc levels of patients and 31 controls were determined by spectrophotometric method. RESULTS: The mean bone mineral density values of patients and controls were 0.661+/-0.201 g/cm2 and 0.751+/-0.175 g/cm2, the mean bone mineral content values were 33.357+/-17.104 g and 38.968+/-14.663 g, and the mean serum zinc levels were 101.2+/-28.8 microg/dl and 108.9+/-15.9 microg/dl, respectively. All controls had normal serum zinc level; however, 11 (39.3%) patients had low serum zinc level (p=0.000). The ratio of patients with Z-score below the -2SD was higher in patients with low zinc level than in patients with normal zinc level (70% vs. 42.8%). CONCLUSIONS: Although insignificant, some of the children with IBD had low levels of serum zinc and these patients had lower Z-scores than the others. Further studies including large numbers of patients may reveal a certain effect of zinc on bone development in patients with inflammatory bowel disease.

An overlap syndrome involving autoimmune hepatitis and systemic lupus erythematosus in childhood.

We report a 12 years old female patient with an overlap syndrome involving autoimmune hepatitis (AIH) and systemic lupus erythematosus (SLE). The patient presented with jaundice, hepatosplenomegaly, malaise, polyarthralgia, arthritis and butterfly rash on the face. Laboratory tests revealed severe liver dysfunction, Coombs positive hemolytic anemia and a positive ANA/anti-dsDNA test. Renal biopsy showed class IIA kidney disease, while liver biopsy showed chronic hepatitis with severe inflammatory activity. The patient satisfied the international criteria for both SLE and AIH. Clinical symptoms and laboratory findings of SLE improved with high dose treatment with corticosteroids and azathioprine, however, remission of the liver disease could not be achieved. Repeat biopsy of the liver after three years of therapy revealed ongoing chronic hepatitis with high level of inflammatory activity. The present case indicates that children with liver dysfunction and SLE should be investigated for AIH. There is much diagnostic and therapeutic dilemma in patients with AIH-SLE overlap syndrome.

Panic disorder in a child with recurrent chest pain.

A 10-year-old boy was admitted to the Pediatric Cardiology Unit with complaints of chest pain and dizziness. Physical examination did not show any pathologic signs. Family history revealed no heart disease and diagnosis of panic disorder (PD) in one of his family members. On follow-up, he was admitted to the pediatric emergency department several times with the same complaint. Organic etiologies of chest pain were excluded by extensive diagnostic work-up. He was referred to the Child and Adolescent Psychiatry Department for further work-up, and PD was diagnosed. A few weeks after starting paroxetine therapy, the frequency and the intensity of the chest pain attacks began to diminish. Early diagnosis of PD will avoid unnecessary investigations and prevent utilization of expensive health services, especially those performed in the emergency department. Physicians should consider that chest pain may be related to psychiatric disorders and refer their patient to mental health professionals for further management. Pharmacological therapy and cognitive-behavioral interventions are successfully used in the management of PD in children and adolescents.