Vladimir Radlovic

HLA genotyping in pediatric celiac disease patients

Celiac disease (CD) is a chronic inflammatory disease in the small intestine triggered by gluten uptake that occurs in genetically susceptible individuals. HLA-DQ2 protein encoded by HLA-DQA1*05 and DQB1*02 alleles is found in 90-95% of CD patients. All of the remaining patients carry HLA-DQ8 protein encoded by HLA-DQA1*03 and DQB1*03:02 alleles. Specific HLA-DQ genotypes define different risk for CD incidence. Presence of susceptible HLA-DQ genotypes does not predict certain disease development, but their absence makes CD very unlikely, close to 100%. Here we presented for the first time the distribution of HLA-DQ genotypes in the group of pediatric celiac patients from the University Childrens Hospital, Belgrade, Serbia and estimated risk for CD development that these genotypes confer. Seventy three celiac disease patients and 62 healthy individuals underwent genotyping for DQA1, DQB alleles and DRB1 allele. 94.5% of patients carried alleles that encode DQ2 protein variant and 2.7% carried alleles that encode DQ8 protein variant. Two patients carried single DQB1*02 allele. No patients were negative for all the alleles predisposing to CD. The highest HLA-DQ genotype risk for CD development was found in group of patients homozygous for DQ2.5 haplotype, followed by the group of heterozygous carriers of DQ2.5 haplotype in combination with DQB1*02 allele within the other haplotype. The lowest risk was observed in carriers of a single copy of DQB1*02 or DQA1*05 allele or other non-predisposing alleles. HLA genotyping, more informative than serological testing commonly used, proved to be a useful diagnostic tool for excluding CD development.

Asymptomatic perforation of large bowel and urinary bladder as a complication of ventriculoperitoneal shunt: Report of two cases

INTRODUCTION Insertion of a ventriculoperitoneal (VP) shunt, the method of choice in the treatment of hydrocephalus, is often followed by various mechanical and/or infective complications. We present two children with asymptomatic perforation of the large bowel and urinary bladder, relatively rare and potentially severe complications of this surgical procedure. OUTLINE OF CASES In both patients a VP shunt was implanted in the first month after birth; in a boy due to congenital hydrocephalus and in a girl due to the consequences of intracranial haemorrhage. Immediately after surgery, as well as during the further course, in both children growth and development were optimal and without any signs of infection or VP shunt malfunction. In the boy at age 6 months and in the girl at age 4 years, without any signs of complications, mothers noted the prominence of the VP shunt tip from the anus in the first case and from the urethral orifice in the second one. The VP shunts were immediately changed, so that both complications were resolved without any consequences. CONCLUSION Insertion of a VP shunt represents the most frequent method of choice of the surgical treatment of hydrocephalus, but also potentially a highly risky procedure followed by various complications about which parents should be informed when patients are children. Owing to adequate approach in the follow-up of children with implanted VP shunt, large bowel and urinary bladder perforation, examples of severe and potentially fatal complications of this surgical intervention, could be disclosed on time and adequately resolved.

Anthropometric and lipid parameters trends in school children: One decade of YUSAD study

INTRODUCTION Athersclerosis is a multifactorial disease that begins in childhood. There are few reports regarding influence of risk factors on the atherosclerotic processes in early period of life and adolescence. OBJECTIVE The aim of this study was to present and analyze risk factor trends in school children over a 10-year period that were included and followed-up by the Yugoslav Study of Atherosclerosis Precursors in School Children (YUSAD Study). METHODS There were three examinations of selected population from 13 centres. The first examination was performed when children were 10 years of age (first group; N = 6381 participants), the second examination on the same population when they were 15 years of age (second group; N = 5017) and third when children were 19/20 years of age (third group; N = 1293). Evaluated parameters included: BMI, waist circumference (WaC) and lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride). RESULTS A significant elevation of values (p < 0.001) of BMI, WaC and triglycerides and a significant decline (p < 0.001) of total cholesterol and LDL cholesterol in boys over 5 and 10-year period was noticed. There was a significant elevation (p < 0.001) of BMI, WaC and HDL values and a significant decline in LDL cholesterol values in girls over the 5 and 10-year period. CONCLUSION Our results point out that girls between 10 and 19/20 years have a better lipid profile during growth. It should be stressed out that childhood and adolescence can be more beneficial in the observation of risk factor influences on pathological, genetic and clinical levels.

Gilbert’s syndrome in children: Our experience

INTRODUCTION Gilberts syndrome represents the most frequent hereditary disorder of bilirubin metabolism. It occurs in 2-7% of subjects in general population, and is manifested by mild unconjugated hyperbilirubinaemia of benign nature. OBJECTIVE The study was conducted in order to analyse our experience related to the circumstances of disclosure, age at onset and sex distribution of Gilberts syndrome in children. METHOD The diagnosis of Gilberts syndrome was based on the findings of mild unconjugated hyperbilirubinaemia in the absence of haemolysis and organic liver disease, as well as significant increase of bilirubin unconjugated fraction in serum after a 3-day hypocaloric diet (400 kcal/daily). RESULTS Of 58 subjects with Gilberts syndrome, there were 40 (68.97%) boys and 18 (31.03%) girls, indicating a 2.22 fold higher incidence of boys than girls. The age at diagnosis of the disorder was similar in boys and girls, and was 12.2-18 (X =14.71 +/- 1.55) years for boys and 10.5-16.4 (X = 14.38 +/- 2.10) years for girls (p > 0.05). Except for 3 girls aged below 12 years, in all other patients the diagnosis was made after that age; in 20, between age 12 and 14 years and in 14, between age 14 and 16 years, while in 10 patents, it was made at age between 16 and 18 years. In 20 (34.48%) subjects, hyperbilirubinaemia was disclosed on routine paediatric examination, in 19 (32.76%) when differentiating the cause of recurrent or acute abdominal pain, in 17 (29.3%) during febrile condition and in 2 during insufficient caloric intake. The values of unconjugated bilirubinaemia, both before a hypocaloric test and after a 3-day energy deprivation, were higher in boys than girls, but this difference was statistically significant only after the 3-day hypocaloric diet in age group between 16 and 18 years (p = 0.038). Also, no significant difference was found in bilirubinaemia level between the different age groups either in boys or girls. CONCLUSION According to our findings, in children, Gilberts syndrome is manifested only in puberty, and 2.22 times more often in boys than girls. It is most frequently revealed during a routine paediatric examination, as well as when investigating the cause of abdominal pain and fever. A significantly higher level of serum bilirubin in boys as related to girls is registered only after a hypocaloric diet in age group between 16 and 18 years.

Pseudoachondroplasia: A case report

INTRODUCTION Pseudoachondroplasia (PSACH) is an autosomal dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein. It is characterized by rhizomelic dwarfism, limb and vertebral deformity, joint laxity and early onset osteoarthrosis. We present the girl with the early expressed and severe PSACH born to clinically and radiographically unaffected parents. CASE OUTLINE A 6.5-year-old girl presented with short-limbed dwarfism (body height 79.5 cm, < P5;-32%) and normal craniofacial appearance and intelligence. The girl was normal until 3 months of age when she expressed growth retardation with apparently shorter extremities in relation to the torso. With age, her rhizomelic dwarfism became increasingly visible, and since completed 15 months of age, when she started to walk, the disease was complicated with genu varum, lumbar lordosis and abnormal gait. Beside visibly short forearms, short, broad and ulnar deviation of the hands, brachydactyly and joint hyperlaxity, the radiographic picture showed markedly flared metaphyses, small and irregular epiphyses and poorly formed acetabulum. CONCLUSION PSACH is an achondroplasia-like rhizomelic dwarfism recognized by the absence of abnormality at birth, normal craniofacial appearance, characteristic epiphyseal and metaphyseal radiographic finding and joint hyperlaxity.

Social, clinical and radiological characteristics of physical abuse of children up to 3 years of age hospitalized in a tertiary health institution

Introduction/Objective: Child abuse is a significant public health problem in modern society. Many cases of violence against children remain undetected. Serbia has no official protocols for medical examination of abused children. The aim of the study is an analysis of the social, clinical and radiological characteristics of physical abuse of children under three years of age that required hospital treatment. Methods: This retrospective study included 98 physically injured children admitted to the University Children’s Hospital in the period from 2013 to 2015, with suspected physical abuse. In addition to the history of injuries, complete clinical examinations and standard laboratory analyses were performed in all children, as well as X-ray examination in children with apparent or suspected skeletal injury. Ultrasound examination and computerized tomography or magnetic resonance imaging were performed in selected patients. Final diagnosis of abuse was established by multidisciplinary assessment team. The children were divided into two groups – those with proven and those with suspected abuse. Results: Most of 98 children who were suspected of being abused (92%) were from one or both un- employed parents, 68% were male, 60% were first-born, and 44% younger than one year. Ninety-two percent of the children had skeletal fractures, 19% of whom had two or more fractures. The commonest fracture was a linear skull fracture, which was detected in 51% of the cases. Abuse was confirmed in only five of 98 suspected cases. Conclusion: Among the known social risk factors for abuse of children, the low economic status of the family was the most frequent one in our analyzed sample. The most common injury is a linear skull fracture. A national guideline for medical investigating of abused children is required.

Late presentation of congenital pseudarthrosis of the clavicle

Congenital pseudarthrosis of the clavicle is a rare clinical entity, first described in 1910. We report on a 15 year old girl, who presented with a painless lump over mid-portion of right clavicle at her routine newborn examination, which was subsequently diagnosed as a congenital pseudarthrosis when she got into adolescence period. Here we explore its pathogenesis, elaborate on its diagnoses and differential diagnoses in paediatric patients, and comment on its distinct treatment.