Tangier disease in a Turkish family.

In this report we describe the upper gastrointestinal tractus involvement in a rare genetic disease of lipid metabolism. A 12-year-old boy presented with sore throat and fever. On physical examination, orange-yellow tonsils and adenoid tissue were noted. Mild hepatosplenomegaly was present. Lipid profile was compatible with Tangier disease (TD). Endoscopy of the upper gastrointestinal tract showed white-yellowish fatty deposits on the gastric mucosa. Microscopically, biopsy specimens contained numerous histiocytes with a foamy cytoplasm packed in the lamina propria of the gastric mucosa and at the crypt basement of the duodenum. His sister, 8 years old, was also diagnosed with TD based on abnormal lipid profile and orange-yellow tonsils. TD is a rare familial disorder of lipid metabolism, characterized by deposition of cholesteryl esters, probably involving the entirety of the gastrointestinal tract from the mouth to the anus.

Gastrointestinal system malformations in children are associated with congenital heart defects.

OBJECTIVE: To determine the frequency of congenital heart defects (CHD) in children with gastrointestinal malformations (GISM) and mortality rates in patients with GISM. METHODS: Two hundred and forty two consecutive children patients with GISM followed up in Pediatric Surgery Clinics of our hospital were examined for cardiovascular anomaly by the Department of Pediatric Cardiology, and the CHD incidence was investigated by examining the records of the patients retrospectively. Chi-square test was used for the statistical analysis of data. RESULTS: Two hundred and forty two patients with gastrointestinal system malformations were included in the study. Of 242 patients, 135 (55.8%) were male and 107 (44.2%) were female, and their age range was 0-15 years. The most frequent GISM were anorectal malformations (43.2%), atresia involving stomach, ileum or colon (21%) and esophageal atresia/tracheoesophageal fistula (18.3%). Congenital heart defects were observed in 28.5% of the participants. The most frequent defects were as follows; atrial septal defect (31 patients, 44.9%) a, ventricular septal defect (17 patients, 24.6%) and patent ductus arteriosus (5 patients, 7.2%). There was no significant difference (p>0.05) in mortality rate in patients with CHD (16.7%) and without CHD (13.3%) undergoing operations for GISM. CONCLUSION: We would like to emphasize the importance of the earliest possible cardiological evaluation of all patients with gastrointestinal system malformations.

A case report of neonatal diabetes due to neonatal hemochromatosis.

A 6-week-old girl, the first child of non-consanguineous parents, was admitted to the hospital for evaluation of vomiting. She was small for gestational age (1500 g). On admission, she weighed 1830 g, and appeared dehydrated. The blood glucose was 880 mg/dL. Insulin and C-peptide levels were <1 microIU/ml and 0.1 pmol/L, respectively. Antibodies of diabetes were negative. The serum triglyceride level was markedly elevated (5322 mg/dL). After a few days of insulin therapy, the triglyceride levels dramatically decreased, but cholestasis persisted. A liver biopsy revealed diffuse iron deposition and the diagnosis of neonatal hemochromatosis was established. In neonatal hemochromatosis, diabetes may occur as a result of iron deposition in the pancreas. The coexistence of neonatal diabetes secondary to neonatal hemochromatosis with a fatal course during the infancy period has not been previously reported. In this report, an infant with neonatal diabetes secondary to neonatal hemochromatosis is presented as the first case in the literature involving the coexistence of these two conditions.

Difficulties in diagnosing sexual abuse in children with condyloma acuminata in Turkey.

Human papillomavirus is responsible for anogenital warts and could be regarded as an indicator of possible sexual abuse in children. A genital wart was detected during an investigation of anti-hepatitis C virus positivity in a four-year-old male patient. No pathological findings of another sexually transmitted disease were found except complete cleft palate and circumferential lesions in the perianal region. No family member was anti-hepatitis C virus positive, but the patient's uncle and his wife had genital condylomata. Although detailed physical examination uncovered no other findings indicative of sexual abuse, suspicion of abuse could not be eliminated. Therefore, we wanted to draw the attention of health professionals to the association of anogenital warts and sexual abuse.

Effect of interferon therapy on glucose metabolism in children with chronic hepatitis B.

The aim of this study was to investigate the effect of interferon (IFN)-alpha treatment on glucose metabolism in children with chronic hepatitis B (CHB). Forty children with CHB received IFN 10 MU/m2 for six months. Oral glucose tolerance test, anti-insulin and anti-glutamic acid decarboxylase (GAD) antibody, fasting plasma C-peptide and insulin (FPI), postprandial insulin, homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-cell, and glucose/insulin ratio (G/I) were measured before and after treatment. The last four parameters were also evaluated in healthy controls (n=42). In patients, fasting plasma glucose (FPG) and HOMA-IR levels were significantly lower than in controls (p = 0.001 and p = 0.020, respectively). There was a strong correlation between degree of liver disease and FPG. Two patients had hyperinsulinemia. HOMA-IR was suppressed in 7 patients enough to indicate increased sensitivity. FPI of 13 patients and HOMA-cell of 9 patients were lower than the minimum level of controls, features compatible with beta-cell hypofunction. Frequency of glucose metabolism abnormalities was not different before and after therapy. After therapy, only 1 patient developed anti-GAD antibody, and FPI of 8 children and HOMA-cell level of 9 children were lower than the minimum level of controls. Hyperinsulinemia was persistent in the same patients. We demonstrated that HBV-infected children had insulin sensitivity; however, no adverse effects of IFN on glucose homeostasis were seen.

An unusual presentation of Wilson's disease in childhood: nodular fatty infiltration in liver.

Wilson's disease is a rare inherited disorder characterized by progressive accumulation of copper in the body tissues. Liver and brain are the most commonly involved organs and the disease is presented predominantly by hepatic manifestations in childhood. Histopathological findings of hepatic involvement may vary from steatosis to end stage cirrhosis. Although diffuse fatty infiltration is a typical finding of Wilson's disease, it can very rarely present in nodular pattern. We report the first case with Wilson's disease who presented with nodular fatty infiltration in the liver in childhood.

Crohn's disease of the vulva in a 10-year-old girl.

Crohn's disease may involve all parts of the gastrointestinal tract and may often involve other organs as well. These non-intestinal affections are termed extraintestinal manifestations. Vulval involvement is an uncommon extraintestinal manifestation of Crohn's disease, and it is very rare in children. Patients with vulval CD typically present with erythema and edema of the labia majora, which progresses to extensive ulcer formation. Vulval Crohn's disease can appear before or after intestinal problems or it may occur simultaneously. We present a 10-year-old girl with intestinal Crohn's disease complicated with perianal skin tags and asymptomatic unilateral labial hypertrophy. The course of her lesion was independent of the intestinal disease and responded significantly to medical treatment including azathioprine and topical steroid. We emphasize that although vulval involvement in childhood is uncommon, Crohn's disease must be considered in the differential diagnosis of nontender, red, edematous lesions of the genital area.

Human tissue transglutaminase antibody screening by immunochromatographic line immunoassay for early diagnosis of celiac disease in Turkish children.

BACKGROUND/AIMS: Celiac disease has a large prevalence worldwide. There are a limited number of comparable epidemiological data for celiac disease in Turkey. The aim of this preliminary study was to determine the prevalence of celiac disease in a sample of 1000 Turkish children by a novel, simple, and visual one-step immunoassay screening test. METHODS: This prospective study consisted of 1000 serum samples from apparently healthy children and children with disorders other than celiac disease aged between 2-18 years who presented as outpatients at Ankara University, Faculty of Medicine, Department of Pediatrics. Sera were tested for IgA-class antibodies against human tissue transglutaminase and gliadin by rapid immunochromatographic line immunoassay. Endomysial antibody IgA against human tissue transglutaminase and AGA IgA/IgG were also tested by ELISA as a second step when the result of the screening test was positive. Small bowel biopsy was recommended to all the children with positive anti-tissue transglutaminase and/or endomysial antibody results. RESULTS: Ten of the 1000 individuals (1%) had positive antibody screening test to human tissue transglutaminase. All tissue transglutaminase-positive samples revealed good correlation with endomysial antibody by ELISA method. Subsequently small bowel biopsy was performed in all serology-positive cases. Biopsy results confirmed a diagnosis of celiac disease in nine cases. The prevalence of biopsy- proven celiac disease was 1:111 (0.9%). CONCLUSIONS: Determination of anti-tissue transglutaminase antibodies by simple visual system for celiac disease appeared to be as reliable as the ELISA system. It is easy to perform and interpret, cost-effective, and rapid, as pointed out in other previous studies, as a screening test in large population-based studies. The prevalence of celiac disease in the overall sample of Turkish children (1:111 or 0.9%) in this preliminary study is similar to that reported in European and Middle Eastern countries and the United States.

HLA types in Turkish children with celiac disease.

The aim of this study was to assess the distribution of human leukocyte antigen (HLA) groups in Turkish children with celiac disease (CD) and to investigate the association of HLA types and clinical manifestations of CD. Seventy-five children with CD were evaluated in two groups: Group I consisted of 45 classical celiac patients (15 males, 6.7+/-3.8 years); Group II consisted of 30 atypical celiac patients (9 males, 9.3+/-4.3 years). The control group consisted of 100 healthy renal transplantation donors. HLA typing was made serologically using standard lymphocytotoxicity techniques. HLA A29, B51, CW5, DR14, DR16, and DQ1 were the most common antigens in the control group. Frequency of HLA B13, CW7, B8, DR7, DR17 and DQ2 was higher in CD patients than in the control group (p<0.005, <0.05, <0.001, <0.001 and <0.001, respectively). The relative risks for HLA DQ2, B8, DR17 and B13 were 14.9, 13.6, 7.1 and 3.6, respectively. Frequency of HLA B35, DR11 and DQ7 was higher in classical CD than atypical CD, while a positive association was found between HLA B8 and atypical CD. A positive association was found between HLA B13, CW7 and DR17 in Turkish celiac patients in addition to HLA B8, DR7 and DQ2. This study also suggested that a correlation may exist between genotype and clinical manifestations.

A rare condition associated with celiac disease: Evans syndrome.

Celiac disease (CD) is one of the most common chronic disorders in childhood. Autoimmune and nonautoimmune disorders including dermatitis herpetiformis, type 1 diabetes mellitus, and autoimmune thyroiditis can be encountered associated with CD. Common hematologic manifestations of CD include anemia owing to iron, folate, or vitamin B12 deficiency. We report a case with CD associated with Evans syndrome of whom to our knowledge, is the first child to be reported in the literature.

The influence of interferon-alpha and combination interferon-alpha and lamivudine therapy on height and weight in children with chronic hepatitis B infection.

AIM: To evaluate the height and weight patterns of children with chronic hepatitis B (CHB) with and without treatment. METHODS: Thirty-four patients with immunoactive CHB randomly assigned to receive interferon-alpha2a (IFN) (5 mIU/m2, 6 months, group I) or IFN (same dose and duration) plus lamivudine (4 mg/kg/day, 24 months) (group II). Fifteen immunotolerant patients (group III) were followed without any treatment. Height (Ht-SDS), weight (Wt-SDS) and growth velocity (GV-SDS) standard deviation scores were monitored for a total of 36 months. RESULTS: Ht-SDS was significantly lower in group II than in group I one year after completion of IFN treatment (p < 0.05). Wt-SDS was significantly higher in group I than the other groups two years after completion of IFN treatment (p < 0.05). In groups I and II, the percentage of children showing abnormal GV-SDS decreased once treatment was completed (p < 0.05). CONCLUSION: CHB does not have deleterious effects on height and weight. Although IFN treatment temporarily compromises weight gain and growth velocity, lamivudine does not have any additional adverse effect.

Effect of interferon treatment on glucose metabolism in children with chronic hepatitis B infection.

BACKGROUND/AIMS: Interferon is known to have some effects on glucose metabolism, but this issue has not been investigated in children with chronic hepatitis B infection. The aim of this study was to investigate the impact of interferon on glucose metabolism and to investigate whether autoimmunity has a role in the pathogenesis. METHODS: Fourteen patients (9 male, 6.3+/-2.7 years) with children with chronic hepatitis B infection were prospectively evaluated. They received interferon 10 MU/m2 for six months. Vral glucose tolerance test, fasting insulin and C-peptide, postprandial insulin and C-peptide, anti-GAD antibody, HOMA-IR and glucose/insulin ratio were measured before and after treatment. RESULTS: Before interferon, oral glucose tolerance test showed glucose intolerance in two patients (14.5%) and hypoglycemia in one patient (7.1%). One patient had hyperinsulinemia and insulin resistance (7.1%), and four patients had hypoinsulinemia and insulin hypersensitivity (28.5%). After interferon, oral glucose tolerance test was normal in 13 patients (92.8%). Abnormal oral glucose tolerance test persisted in the same patient, but no difference was found in insulin resistance. Hypoinsulinemia and insulin hypersensitivity were present in five patients (35.7%). DM related autoantibodies were negative in all patients before interferon; however, one patient, whose glucose metabolism was within normal limits, developed anti-GAD antibody after interferon. CONCLUSIONS: Children with children with chronic hepatitis B infection were shown to have hypoinsulinemia and insulin hypersensitivity. These children may have risk of progresssing to insuline dependent drabetes mellitus. We demonstrated that interferon did not seem to worsen glucose metabolism, but it had minimal positive impact on it. These results should be supported with other studies and interferon should be used carefully, especially in children with decreased beta cell reserve.

Autoantibodies in children with chronic hepatitis B infection and the influence of interferon alpha.

BACKGROUND/AIMS: One of the serious side effects of interferon-a (IFN) is the possible induction of autoimmunity. However, data concerning children with chronic hepatitis B (HBV) infection is limited with conflicting results. The aim of this study was to evaluate the frequency of autoantibody positivity in children with chronic HBV infection and to assess whether IFN treatment has any influence on exacerbation of serological or clinical parameters of autoimmunity. METHODS: 61 children (32 female, mean age 7.5+/-3.8 years) were evaluated in two groups. Group I (29 patients) received 5 x 106 U/m2 IFN-a and group II (32 patients) 10 x 106 U/m2 IFN-a three times per week for six months. Autoantibody levels (anti-TPO, anti-Tg, AMA, ASMA, LKM-1, ANA, ds-DNA) and Ig G, A and M were analyzed before and after IFN treatment and 12 months after completion of therapy. RESULTS: No significant difference in autoimmune antibody positivity rate was observed between the two groups when compared at the beginning of the study and at the end of IFN treatment separately. SMA positivity rate was shown to significantly increase in group I after treatment was completed (p<0.05). None of the patients positive for autoantibodies showed further laboratory or clinical signs of autoimmunity. Thyroid hormones were within normal range in patients positive for anti-thyroid antibodies; however, thyrotropin-releasing hormone (TRH) stimulation test revealed subclinical hypothyroidism. All antibodies disappeared 12 months after completion of therapy. Overall, autoantibody positivity, pre- and posttreatment, were 16.3% and 54%, respectively (p<0.05). Age, sex, hepatitis activity index (HAI) score, HBV load and the dose of IFN had no influence on autoantibody formation. Complete and sustained response rates were similar in children with and without autoantibody. CONCLUSIONS: Autoantibody formation may occur in children with chronic HBV infection. IFN treatment leads to significant autoantibody formation, but this causes no organ dysfunction except for antithyroid antibodies associated with subclinical hypothyroidism. These results suggest that neither the presence of autoantibodies in choronic hepatitis B nor their development during IFN therapy is associated with severe autoimmune disorders in children with chronic HBV infection.

Central pontine myelinolysis secondary to cytomegalovirus hepatitis in a 10-month-old child.

We present a 10-month-old child with central pontine myelinolysis (CPM) secondary to chronic active hepatitis due to cytomegalovirus (CMV) infection. A total of 35 paediatric cases of pontine and/or extrapontine myelinolysis are reported and, to our knowledge, CPM secondary to CMV hepatitis in an infant has not been previously reported. The MRI findings are highlighted.