Search

ObjectiveTo analyze the mutational spectrum, clinical characteristics, genotype–phenotype correlations, testicular adrenal rests tumor prevalence, and role of neonatal screening in congenital adrenal hyperplasia (CAH) patients from Slovakia and Slovenia.Design and methodsData were obtained from 104 patients with CAH registered in Slovak and Slovenian databases. Low-resolution genotyping was performed to detect the most common point mutations. To detect deletions, conversions, point mutations, or other sequence changes in the CYP21A2 gene, high-resolution genotyping was performed. Genotypes were classified according to residual 21-hydroxylase activity (null, A, B, C).Results64% of the individuals had the salt-wasting form (SW-CAH), 15% the simple virilizing form (SV-CAH), and 21% the non-classic (NC-CAH). CYP21A2 gene deletion/conversion and c.293-13A/C>G pathogenic variant accounted together for 55.5% of the affected alleles. In SV-CAH p.Ile172Asn was the most common pathogenic variant (28.13%), while in NC-CAH p.Val282Leu (33.33%), CYP21A2 gene deletion/conversion (21.43%), c.293-13A/C>G (14.29%), Pro30Leu (11.90%). The frequency of alleles with multiple pathogenic variants was higher in Slovenian patients (15.83% of all alleles). Severe genotypes (0 and A) correlated well with the expected phenotype (SW in 94.74% and 97.3%), while less severe genotypes (B and C) correlated weaklier (SV in 50% and NC in 70.8%). The median age of SW-CAH patients at the time of diagnosis was 6 days in Slovakia vs. 28.5 days in Slovenia (p=0.01). Most of the Slovak patients in the cohort were detected by NBS. (24 out of 29). TARTs were identified in 7 out of 24 male patients, of whom all (100%) had SW-CAH and all had poor hormonal control. The median age at the diagnosis of TARTs was 13 years.ConclusionThe study confirmed the importance of neonatal screening, especially in the speed of diagnosis of severe forms of CAH. The prediction of the 21-OH deficiency phenotype was reasonably good in the case of severe pathogenic variants, but less reliable in the case of milder pathogenic variants, which is consistent compared to data from other populations. Screening for TARTs should be realized in all male patients with CAH, since there is possible remission when identified early.

Proopiomelanocortin (POMC) deficiency is an extremely rare inherited autosomal recessive disorder characterized by severe obesity, adrenal insufficiency, skin hypopigmentation, and red hair. It is caused by pathogenic variants in the POMC gene that codes the proopiomelanocortin polypeptide which is cleaved to several peptides; the most notable ones are adrenocorticotropic hormone (ACTH), alpha- and beta-melanocyte-stimulating hormones (α-MSH and β-MSH); the latter two are crucial in melanogenesis and the energy balance by regulating feeding behavior and energy homeostasis through melanocortin receptor 4 (MC4R). The lack of its regulation leads to polyphagia and early onset severe obesity. A novel MC4R agonist, setmelanotide, has shown promising results regarding weight loss in patients with POMC deficiency. A systematic review on previously published clinical and genetic characteristics of patients with POMC deficiency and additional data obtained from two unrelated patients in our care was performed. A 25-year-old male patient, partly previously reported, was remarkable for childhood developed type 1 diabetes (T1D), transient growth hormone deficiency, and delayed puberty. The second case is a girl with an unusual presentation with central hypothyroidism and normal pigmentation of skin and hair. Of all evaluated cases, only 50% of patients had characteristic red hair, fair skin, and eye phenotype. Central hypothyroidism was reported in 36% of patients; furthermore, scarce adolescent data indicate possible growth axis dysbalance and central hypogonadism. T1D was unexpectedly prevalent in POMC deficiency, reported in 14% of patients, which could be an underestimation. POMC deficiency reveals to be a syndrome with several endocrinological abnormalities, some of which may become apparent with time. Apart from timely diagnosis, careful clinical follow-up of patients through childhood and adolescence for possible additional disease manifestations is warranted.

Objectives: Early identification of children at risk of atherosclerosis is of paramount importance for implementing primary preventive measures addressing vascular health. Carotid intima-media thickness (cIMT) is a non-invasive biomarker of atherosclerosis. Semiautomatic radiofrequency-based software-guided technique quality intima-media thickness (RF-QIMT) was used to determine cIMT normative values in a healthy cohort of Caucasian children aged 6 to 18 years.Study design: In a cross-sectional study, data on age, chronic illness, medication use, and pubertal status was acquired by a questioner. Anthropometric and blood pressure measurements were performed by standardized methods and trained medical personnel. cIMT of the right common carotid artery far wall (1 centimeter proximal to bifurcation) was determined using a multifrequency (3–13 MHz) electronic linear array transducer SL1543, a portable ultrasound device (MyLab Gamma Esaote, Genoa, Italy), and RF-QIMT software. A systematic review of the published normal cIMT in children was done using PRISMA methodology, and identified normative values were compared to those obtained in the presented study.Results: 1137 non-obese normotensive children (males: n = 512; mean age 12.04 ± 3.52 years, females: n = 625, mean age 12.98 ± 3.83 years) were included. Gender-, age-, and height-specific mean cIMT percentile tables, percentile charts, and LMS tables for the RF-QIMT method were provided. They were comparable to the previously published data on mean cIMT gained by other validated ultrasound imaging techniques. cIMT increased with age, height, hip circumference, and BMI and was higher in males.Conclusions: Gender-, age-, and height-specific normative cIMT values, using the semiautomatic software-guided RF-QIMT technique, in children aged 6 to 18 years were developed and validated in respect to the previously published pediatric normative cIMT data. It is suggested that the investigated method could be used for the estimation of atherosclerotic risk in children, especially in epidemiological studies.

Background and Objectives. Familial non-autoimmune autosomal dominant hyperthyroidism (FNAH) is a rare cause of childhood hyperthyroidism. It is caused by the thyroid-stimulating hormone receptor (TSHR) gene variants. So far, only around 40 families with FNAH have been reported. Patients with activating TSHR variants demonstrated the same classical signs and symptoms of hyperthyroidism as seen in patients with Graves’ disease. Since 2012, ablative therapy is recommended to avoid relapses of hyperthyroidism and its consequences. Case Presentation. We presented a young adult male patient with a novel heterozygous TSHR disease-causing variant p.Arg418Lys (c.1253G>A) in the exon 10, who presented with a mild but progressive FNAH, with a follow-up since infancy. Discussion. Constantly suppressed TSH, including during the euthyreosis in childhood and hypothyreosis after iodine ablation therapy, suggested central dysregulation of the TSH secretion.

Background/Aim: To estimate overweight and obesity prevalence trends in Slovenian adolescents entering secondary schools in the years 2004, 2009 and 2014 and differences in the prevalence between different types of secondary schools. Methods: Data from 17,538 adolescents entering secondary schools (mean age ± standard deviation 15.4 ± 0.5 years) collected during obligatory medical examination in years 2004, 2009 and 2014 was analyzed. Overweight and obesity were defined using International Obesity Task Force criteria. Results: In 2004-2009 overweight and obesity prevalence increased, especially in males and stabilized thereafter (2009-2014) in both genders. It was significantly higher (p Conclusions: Overweight and obesity prevalence in Slovenian adolescents entering secondary schools stabilized recently. Adolescents attending secondary vocational and technical/professional schools are at an increased risk of overweight and obesity.

AIMS/HYPOTHESIS: The excessive accumulation of adipose tissue in the obese state is linked to an altered secretion profile of adipocytes, chronic low-grade inflammation and metabolic complications. RBP4 has been implicated in these alterations, especially insulin resistance. The aim of the present study was to determine if a local inflammatory micro-environment in adipose tissue regulates RBP4 expression and secretion. METHODS: Human SGBS and primary adipocytes cultured with conditioned media from human THP-1 macrophages were used as an in vitro model for adipose inflammation. Adipocytes were exposed to recombinant TNF-α, IL-1β, IL-6 or IL-8. In addition, coexpression of IL-1β and RBP4 was measured in adipose tissue samples from 18 healthy females. RBP4 expression was studied by quantitative PCR and ELISA. RESULTS: RBP4 mRNA expression and secretion was significantly reduced upon incubation with macrophage-conditioned media in SGBS adipocytes and human primary adipocytes. Out of several factors studied we identified IL-1β as a new factor regulating RBP4. IL-1β significantly downregulated RBP4 mRNA and secretion in a time- and dose-dependent manner. IL-1β mediated its inhibitory effects on RBP4 expression via IL-1 receptor and NF-κB, as incubation with the IL-1 receptor blocking antibody and the NF-κB inhibitors CAPE and SC-514 reversed its effect. Most interestingly, RBP4 mRNA was negatively correlated with IL-1β mRNA in subcutaneous adipose tissue. CONCLUSIONS: Adipose tissue inflammation as found in the obese state might lead to a downregulation in local RBP4 levels. IL-1β was identified as a major factor contributing to the decrease in RBP4. The increase in circulating RBP4 that often precedes the development of systemic insulin resistance is most likely unrelated to inflammatory processes in adipose tissue.

Sindrom Prader-Willi (PWS) je kompleksna genetska motnja, ki je posledica pomanjkljivega izražanja genov na kromosomski regiji 15q, za katero so značilne hipotonija, težave s hranjenjem in čustveno-vedenjske težave. Celostna obravnava vključuje somatsko zdravljenje z nadomeščanjem rastnega hormona kot tudi z drugim medikamentnim zdravljenjem npr. zdravljenje depresije, motnje pozornosti, psihoze. Poleg tega pa so ključnega pomena nemedikamentni ukrepi: dietetična in fiziatrična obravnava ter opremljenost z medicinskimi pripomočki in vedenjske strategije. V prispevku prikazujemo celostno obravnavo otrok s sindromom Prader-Willi, kot se izvaja v Centru za izobraževanje, rehabilitacijo in usposabljanje CIRIUS Kamnik od vstopa v šolo do končanega šolanja oziroma do dopolnjenega 26. leta starosti. Predstavimo kohorto otrok z genetsko potrjenim PWS (starost 11.4 ± 3.1 let, od tega 4 fantje in 1 dekle) in način zdravstvene obravnave v naši ustanovi s spremljanjem pri dietetiku, merjenjem telesne sestave (z elektronskim analizatorjem BIVA) in z individualnimi prehranskimi ukrepi, s fiziatrično obravnavo s predpisovanjemm medicinskih pripomočkov in psihološko obravnavo, kar vse prispeva k njihovi boljši funkcionalnosti in obvladovanju stanja. Na prikazu primerov so predstavljeni tudi praktični napotki, kako ravnati v specifičnih vedenjskih situacijah.

Prader-Willi syndrome (PWS) is a complex genomic imprinting disorder of chromosomal region 15q, characterized by hypotonia, feeding problems, and emotional-behavioural problems. Comprehensive treatment includes pharmacological therapy with the replacement of growth hormone as well as other pharmacological therapies against, e.g., depression, attention disorders, and psychosis. In addition, non-pharmacological measures and behavioural strategies are the keys to caring for these patients. We present a comprehensive treatment of children with Prader-Willi syndrome as implemented at our Centre for Education, rehabilitation, and Training CIRIUS Kamnik. We present a cohort of children with genetically confirmed PWS (n=5; age=11.4 ± 3.1 years, of which four were boys) and comprehensive follow-up we offer with dietary counselling, body content measurement (with electronic device BIVA), physiatry treatment with the prescription of medical devices and psychological treatment, all of which contribute to their better functionality and control of the condition. The paper also presents practical instructions on how to act in specific behavioural situations, using examples.

Background: Slovenian children are facing considerable health challenges from the rapid social changes that influence their opportunity to engage in daily physical activity. Objective: To overlay the social changes to the established Report Card model as a means of contextualising the extreme changes in physical activity and fitness observed over several years. Methods: Benchmarks were graded for 10 core indicators, plus two (Sleep, Seasonal Variations). Active Healthy Kids Slovenia members met (predominantly via zoom) liaising with team leader(s) on a flexible, individual basis, based on coronavirus disease 2019 (COVID-19) regulations, over the ∼2-year assessment period of the project. Data were separated to the years prior to, ‘pre’ 2018–2020, and ‘during’ the global pandemic (2020–2021). Where sufficient data existed for both timeframes, grades were averaged to produce an overall grade. Results: Grade results are expressed as pre/during/final grade, where the final grade (bolded) is a straight average of the two preceding time epochs: Overall Physical Activity (A-/A-/A-), Organized Sport and Physical Activity (C+/C/C), Active Play (D/C+/C), Active Transport (C/INC/C), Sedentary Behaviour (B/C/C+), Physical Fitness (A+/A-/A), Family and Peers (B+/INC/B+), Schools (A/A/A), Community and Environment (A+/A+/A+), Government (A/F/D), Sleep (D-/INC/D-), Seasonal Variations (D/C-/D+). Conclusion: Although Slovenia has some of the most consistently physically-active children in the world, the effects of the COVID-19 pandemic exerted significant reductions in physical activity opportunities, and especially when coupled with funding re-distributions, resulted in the steepest decline of child physical fitness observed within the >35-year history of Slovenia's well-established national fitness surveillance system.

Uvod: Motnje v razvoju spola (DSD) se pojavijo pri približno 1/5000 živorojenih otrok. Med nedavno odkritimi genetskimi vzroki za 46,xY DSD so različice v genu NR5A1, ki so odgovorne za širok fenotipski razpon. Prikaz primera: Predstavljamo primer donošenega novorojenčka z dvoumnimi genitalijami: levostransko tipno gonado v levi urogenitalni gubi volumna 1 ml, ter desnostransko tipno gonado v dimljah, odsotnost gubanosti in hiperpigmentacije kože urogenitalnih gub, kratek genitalni tuberkel dolžine 1,5 cm, labioskrotalni meatus sečnice (ocena zunanjih genitalij 4). Ultrazvok je pokazal prisotnost spolnih žlez, ki so kompatibilne s testisi, moški tip sečnice in odsotnost maternice ali jajčnikov. Kariotip je bil 46,xY in NGS je odkril patogeno heterozigotno podvajanje enega nukleotida 614dupC v genu NR5A1. Glede na to je bil določen moški spol in pri 8 mesecih je imel majhno strukturo penisa z dolžino < 2 cm, brez razvitega skrotuma in labioskrotalno hipospadijo. Orhidopeksija je bila opravljena v starosti 14 mesecev. Histologija gonad je kazala na prepubertetni testis. Razprava: Različice NR5A1 imajo spremenljivo ekspresivnost in nepopolno penetranco. Klinična slika pri bolnikih 46,xY s patogeno različico v genu NR5A1 sega od dvoumnih genitalij do normalnih ženskih zunanjih genitalij z virilizacijo v puberteti. Zdi se, da razvoj v puberteti ni močno povezan s stopnjo virilizacije ob rojstvu, saj velika večina kaže znake virilizacije v puberteti.

Introduction: Differences of Sex Development (DSD) occur in approximately 1/5000 live births. One of the recently found genetic causes for 46, xY DSD is NR5A1 gene variants, responsible for a broad phenotypic spectrum. Case Report: We present a case of a full-term newborn with ambiguous genitalia: one gonad located in the urogenital fold, the other inguinal, absence of wrinkling or hyperpigmentation of the urogenital folds’ skin, the short genital tubercle, and labio-scrotal urethral meatus (External Genital Score of 4). Male-type urethra and the absence of a uterus or ovaries were determined by ultrasound. The karyotype was 46, xY, and a pathogenic heterozygous single nucleotide duplication 614dupC in the NR5A1 gene was found by NGS. The decided gender of rearing was male. Orchidopexy was performed at age 14 months. The histology of the gonad was indicative of a prepubertal testis. Discussion: NR5A1 variants have variable expressivity and incomplete penetrance. 46, xY patients with a pathogenic variant in the NR5A1 gene range from ambiguous genitalia to normal female external genitalia with virilization at puberty. Pubertal development does not strongly correlate to the degree of virilization at birth, with the majority showing signs of virilization at pubertal age.

Relative energy deficiency syndrome develops in children and adolescents as a result of a negative energy balance due to insufficient energy intake during intense physical exercise regimens. This energy imbalance leads to impaired physiological function of multiple organ systems. Moreover, in children and adolescents, it presents a risk for the development of long-term consequences in terms of negative effects on growth, pubertal development and bone health. Early recognition and management are therefore crucial in this age group. Due to poor awareness among young athletes, their parents, coaches, medical staff, and a non-specific clinical presentation the illness is often overlooked.

Sindrom relativnega energijskega primanjkljaja se razvije pri otrocih in mladostnikih športnikih ob negativni energijski bilanci, ki je posledica nezadostnega vnosa energije glede na velike potrebe ob intenzivni telesni vadbi. Energijsko neravnovesje privede do motenj v delovanju več organskih sistemov. Pri otrocih in mladostnikih so posledice lahko dolgoročne in se kažejo kot neugoden vpliv na rast, pubertetni razvoj in zdravje kosti. Zgodnji prepoznava in obravnava sta tako v tej starostni skupini ključni. Zaradi pomanjkljive ozaveščenosti med mladimi športniki, njihovimi starši, trenerji in zdravstvenim osebjem ter nespecifične klinične slike bolezen pogosto spregledamo.

Hypocalcaemia is a common disorder of calcium and phosphate metabolism in children, especially in newborns. It is often asymptomatic; clinical signs and symptoms are dependent on the age of the child. The primary care physician can confirm hypocalcaemia in the child with a suspicious clinical picture and clinically stabilise the child. Further laboratory and imaging diagnostics should be performed at the secondary and most often the tertiary level of medical care. In the article, the case of a girl with clinically manifested hypocalcaemia, caused by primary hypoparathyroidism as a consequence of autoimmune polyglandular syndrome type 1, is presented.

Hipokalcemija je pogosta motnja v presnovi kalcija in fosfata pri otrocih, zlasti pri novorojenčkih. Pogosto ne povzroča simptomov. Simptomi in znaki so odvisni od otrokove starosti. Na primarni ravni zdravstvene obravnave zdravnik diagnozo hipokalcemija potrdi z laboratorijsko analizo krvi in otroka klinično stabilizira. Nadaljnjo laboratorijsko in slikovno diagnostično obravnavo opravimo na sekundarni oz. največkrat na terciarni ravni. V prispevku predstavljamo primer deklice s klinično izraženo hipokalcemijo zaradi primarnega hipoparatiroidizma ob avtoimunskem poliglandularnem sindromu tipa 1.

Duchennova mišična distrofija (DMD) je najpogostejša in ena najresnejših mišičnih bolezni otroške dobe. Gre za na kromosom X vezano recesivno živčno-mišično bolezen, ki jo povzroča mutacija v genu za distrofin. Primarno prizadene skeletne mišice in srčno mišico. Pri večini dečkov se klinični znaki bolezni izrazijo z napredujočo mišično šibkostjo med 3. in 5. letom starosti. Mišična šibkost je bolj izražena v proksimalnih kot distalnih mišicah in v začetni fazi bolj vpliva na poslabšanje funkcije spodnjih kot zgornjih udov. Bolezen postopno napreduje. Pri nezdravljenih otrocih večinoma po 11. do 12. letu starosti vodi v takó resno zmanjšanje zmožnosti gibanja, da le-ti že za premagovanje krajših razdalj potrebujejo invalidski voziček. Napredujoča šibkost dihalnih mišic vodi v kronično dihalno odpoved in potrebo po pomoči pri predihavanju. Okvara funkcije srca je splošno prisotna, kajti po študijah so klinični znaki kardiomiopatije prisotni pri vseh bolnikih po 18. letu starosti. Na podlagi klinične slike diagnozo DMD potrdimo z laboratorijskimi in genetskimi preiskavami. V primeru negativnih rezultatov genetskih preiskav, a ob močnem kliničnem sumu za DMD, pa se za potrditev diagnoze poslužujemo mišične biopsije. Zdravljenje bolnikov z DMD zahteva multidisciplinarno obravnavo. Z uporabo kortikosteroidov (KS), fizioterapije, podpornega zdravljenja in opreme s pripomočki sta se življenjska doba in kakovost življenja bolnikov z DMD izboljšala. V fazi razvoja je več zdravil, katerih delovanje se usmerja v zmanjšanje okvare mišic, a tudi zdravil, ki bi odpravile osnovni, tj. genetski vzrok bolezni.

Ectopic thyroid gland is a rare clinical entity characterized by thyroid tissue in a location other than its normal anatom- ical position. It is a developmental abnormality. The most frequent location of ectopic thyroid is at the base of the tongue, although it can be found elsewhere along the path of thyroid embryogenic descent and even at distant body locations. Single ectopy is the most common, but dual and triple ectopy has also been described. Most people with ectopic thyroid are asymptomatic. If symptoms occur, they are related to the location and size of the ectopic tissue as well as its endocrine dysfunction. The most important diagnostic procedure for detection of ectopic thyroid tissue is scintigraphy. For patients with- out symptoms, no treatment is necessary, but they need regular follow-up and action if symptoms appear. Patho- logical changes can occur in the ectopic as in the ortho- topic gland. We present a rare case of dual ectopy with subclinical hypo- thyroidism in a two-and-a-half-year-old girl and a review of cases of ectopic thyroid diagnosed in a 5-year period at the University Children’s Hospital Ljubljana.

Ščitnica je ektopična, če ščitnično tkivo leži na netipičnem anatomskem mestu. Je posledica motnje v njenem embri- onalnem razvoju. Najpogosteje se nahaja na korenu jezi- ka, najdemo pa jo tudi drugje v poteku spusta ščitnice med embriogenezo in celo na oddaljenih mestih. Večinoma je enojna, redkeje pa opisujejo tudi primere dvojne ali celo trojne ektopije. Osebe z ektopično ščitnico navadno nimajo nikakršnih simptomov. Sicer so simptomi odvisni od lege in velikosti ektopičnega tkiva ter od njegove endokrine disfunkcije. Najpomembnejša preiskava za opredelitev mesta ektopične ščitnice je scintigrafija. »eprav pri brezsimptomnih bolnikih zdravljenje ni potrebno, moramo poskrbeti za redno slede- nje in ustrezno ukrepanje ob pojavu zapletov. Podobno kot v ortotropni ščitnici lahko tudi v ektopični ščitnici pride do bolezenskih sprememb. V prispevku predstavljamo redek primer dvojne ščitnične ektopije s subkliničnim hipotiroidizmom pri dve in pol letni deklici in podajamo pregled primerov ektopične ščitnice, ki smo jih v 5-letnem obdobju diagnosticirali na Pediatrični kliniki Ljubljana.

Monogenic obesity is a severe, genetically determined disorder that affects up to 1/1000 newborns. Recent reports on potential new therapeutics and innovative clinical approaches have highlighted the need for early identification of individuals with rare genetic variants that can alter the functioning of the leptin-melanocortin signalling pathway, in order to speed up clinical intervention and reduce the risk of chronic complications. Therefore, next-generation DNA sequencing of central genes in the leptin-melanocortin pathway was performed in 1508 children and adolescents with and without obesity, aged 2-19 years. The recruited cohort comprised approximately 5% of the national paediatric population with obesity. The model-estimated effect size of rare variants in the leptin-melanocortin signalling pathway on longitudinal weight gain between carriers and non-carriers was derived. In total, 21 (1.4%) participants had known disease-causing heterozygous variants (DCVs) in the genes under investigation, and 62 (4.1%) participants were carriers of rare variants of unknown clinical significance (VUS). The estimated frequency of potential genetic variants associated with obesity (including rare VUS) ranged between 1/150 (VUS and DCV) and 1/850 (DCV) and differed significantly between participants with and without obesity. On average, the variants identified would result in approximately 7.6 kg (7.0-12.9 kg at the 95th percentile of body weight) (girls) and 8.4 kg (8.2-14.4 kg) (boys) of additional weight gain in carriers at age 18 years compared with subjects without obesity. In conclusion, children with a genetic predisposition to obesity can be promptly identified and may account for more than 6% of obesity cases. Early identification of genetic variants in the LEPR, PCSK1, POMC, MC3R and MC4R genes could reduce the societal burden and improve the clinical management of early severe childhood obesity and its implementation should be further investigated.

Abstract Background Primary brain calcification (PBC), a neurodegenerative disorder with characteristic calcium deposits in the basal ganglia and other brain areas, typically presents with various neurological and psychiatric symptoms in the fourth or fifth decade of life or later. We present the case of a patient with psychiatric manifestations much earlier than usual, in the second decade of life. Case presentation The case of an adolescent female with acute psychotic symptoms, emotional instability, disorganized and suicidal behavior, stereotypical movements, below average intelligence and a three-year history of headaches is reported. Among others, the presentation included tactile hallucinations with secondary hypochondriacal delusions, which are rarely described in this diagnosis. Massive calcinations in the area of the basal ganglia and thalamus were determined by computerized tomography. Other causes of brain calcification were excluded. No causative mutations were found in selected genes. All the symptoms apart from lower intellectual abilities improved with quetiapine and sertraline. The patient showed no side effects. Conclusions This case report highlights the successful use of quetiapine for symptomatic treatment of acute psychosis due to PBC in an adolescent without exacerbating extrapyramidal symptoms.

A Caucasian girl with consanguineous parents presented with early severe obesity and retinal dystrophy. A novel, homozygous gene truncating variant (c.1897C>T) in the INPP5E gene confirmed the diagnosis of MORMS (OMIM #610156). A novel clinical finding in the presented syndrome is progressive cone-rod type retinal dystrophy diagnosed at the age of four months that progressed in the 1st decade of life. Severe obesity, insulin resistance with hyperinsulinism, and impaired glucose tolerance developed alongside other components of the metabolic syndrome - dyslipidemia, arterial hypertension, and obstructive hypopnea in sleep. At the age of 14 years, primary amenorrhea persists. The patient is managed by regular nutritional advice, metformin, antihypertensive medication, and non-invasive respiratory support during sleep. Differential diagnosis of this rare entity is discussed in extend.

Introduction: Adolescent and children obesity is a growing concern worldwide. Bariatric surgery is used as an effective treatment for adolescents with obesity and provides physical and mental health benefits. Application of alternative, minimally invasive, safe, and reversible endoscopic procedures, such as the Duodenojejunal bypass liner (DJBL), has been recently suggested as an effective treatment for adolescents with obesity. We explored specific psychological outcomes of adolescents with obesity during a year of follow-up after undergoing a reversible endoscopic bariatric procedure, and a year after removal. We were also interested in identifying psychological factors that could predict successful weight loss after the procedure.Methods: Nineteen adolescent with severe obesity undergoing DJBL procedure were psychologically assessed in an open-label, prospective clinical trial (NTC0218393), at the implantation of device and at the removal of device after 12 months. Control group of 26 adolescents with severe obesity were recruited from the same outpatient clinic undergoing only conservative treatment. In addition, adolescents from the intervention group were followed for 12 months after the removal of the device. The Youth Self Report (YSR) was used to assess adolescents' emotional and behavioural problems; The Multidimensional Body-Self Relations Questionnaire (MBSRQ) to assess body image and The Eating Disorder Examination Questionnaire (EDE-Q) to assess attitudes and behaviours related to eating disorder.Results: Significant improvements in somatic complain (F = 12.478, p = 0.001), emotional and behavioural problems (F = 7.169, p = 0.011) and food restraining (F = 9.605, p = 0.004) were found in the intervention group at device removal compared to the control group. Moreover, at the time of device removal compared to baseline, improvements in several psychological outcomes were found (F = 32.178 p = 0.000 for emotional and behavioural problems). Adolescents also became more satisfied with their appearance (F = 6.789, p = 0.019). Majority of observed changes remained stable at the next follow up a year after the device removal. Significant predictors of successful weight loss at device removal were fewer overeating episodes (B = 0.147, p = 0.022) and lower body satisfaction (B = 0.932, p = 0.013).Discussion: Following a reversible bariatric procedure, improvements of psychological (emotional and behavioural) factors were found in adolescents with severe obesity. Psychological predictors of successful weight loss were identified, showing the greatest importance of eating behaviour and body satisfaction in successful weight loss.

Linear growth is the result of bone elongation in children and adolescents mediated by processes of endochondral ossification and maturation of bone tissue. Physical activity (PA) importantly influences both processes through systemic and local effects, mediated by growth hormone, insulin-like factor I, sex hormones, thyroid hormones, glucocorticoid hormones and various cytokines with endo-, para- and autocrine function, secreted by adipose tissue (adipokines) or muscles (myokines). It is important to promote a physically active lifestyle already in early childhood as it tends to persist into adulthood together with favorable body composition. From the safety point-of-view, recent data suggests that PA does not negatively influence linear growth regardless of its duration or intensity, as long as chronic negative energy balance is prevented by sufficient energy intake. The aim of this review is to describe current scientific knowledge on the mechanisms by which PA could influence linear growth and present recent studies analyzing its possible effects.

Adrenal bleeding in a newborn is rare. The cause of bleeding is unknown, most likely due to several factors. Bleeding may be minimal with no clinical signs or fulminant with acute adrenal insufficiency, which is a life-threatening situation that requires immediate detection and treatment. In this paper we represent a clinical case of a term neonate born to the mother with gestational diabetes, who was hospitalised due to high early hyperbilirubinemia. Significant bleeding in both adrenal glands was identified by ultrasound and primary adrenal insufficiency diagnosed. We discuss possible causes, the diagnostic clues, the treatment of disease and its prognosis.

Cricopharyngeal achalasia is an uncommon cause of dysphagia, especially in children. Congenital form is known in neonates and infants. In older children this disease has been reported in very rare cases and mostly in connection with neurological and muscular diseases. We present a case of a 12-year-old girl with a four-year history of dysphagia. Esophagogastroduodenoscopy, radiological contrast swallow study and esophageal manometric study confrmed the diagnosis of cricopharyngeal achalasia. Te patient was successfully treated with dilatation of the upper esophageal sphincter. An initial attempt of dilatation appears to be a safe and effective option in the management of cricopharyngeal achalasia in children, and may prevent or at least postpone the need for myotomy. Following the diagnosis of cricopharyngeal achalasia, several autoimmune conditions were diagnosed. Our case report revealed that cricopharyngeal achalasia may occur in association with some other autoimmune conditions, and that autoimmunity may also play a role in cricopharyngeal achalasia itself

Background: In the last twenty years a marked rise in overweight and obesity among children and adolescents in developed countries was observed. Obesity in this age group is a significant risk factor for type 2 diabetes and cardiovascular diseases in adulthood. So far no comparative data on overweight and obesity in Slovene children and adolescents existed. In our study the data collected during preventive examinations of five-year-old and adolescents was analysed and guidelines for management of children with high body mass index (BMI) were proposed.Methods: Using the methods of descriptional statistics the data on BMI of 4685 randomly collected five-year-old children and 2474 randomly collected adolescents aged 15–16 years were analysed. Data was collected in the years 2003–2005, evaluated according to the international reference values, and compared to other populations.Results: The prevalence of overweight among five-year-old children is 18.4% and 20.9% in boys and girls respectively. The obesity criteria are fulfilled in 9.0% boys and 7.9% girls. Among adolescents 17.1% boys and 15.4% girls are overweight and 6.2% boys and 3.8% girls are obese. These results indicate that the prevalence of obesity in Slovenia is similar as in other developed European countries.Conclusions: The study showed that obesity in childhood and adolescence in Slovenia is a problem that deserves more concern in medical institutions and on national level. Further research on reasons for this condition and new programs for stimulation of physical activity and healthy nutrition of children and adolescents are warranted.