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Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare, X-linked recessive multisystem lysosomal storage disease due to iduronate-2-sulfatase enzyme deficiency. We presented three unrelated Slovenian patients with the severe form of MPS II that received three different management approaches: natural course of the disease without received specific treatment, enzyme replacement therapy (ERT), and hematopoietic stem cell transplantation (HSCT). The decision on the management depended on disease severity, degree of cognitive impairment, and parent’s informed decision. The current benefits of MPS II treatments are limited. The lifelong costly intravenous ERT brings significant benefits but the patients with severe phenotypes and neurological involvement progress to cognitive decline and disability regardless of ERT, as demonstrated in published reviews and our case series. The patient after HSCT was the only one of the three cases reported to show a slowly progressing cognitive development. The type of information from the case series is insufficient for generalized conclusions, but with advanced myeloablative conditioning, HSCT may be a preferred treatment option in early diagnosed MPS II patients with the severe form of the disease and low disease burden at the time of presentation.

Rare diseases (RDs), with distinctive and complex features, pose a serious public health concern and represent a considerable challenge for the Slovenian healthcare system. One of the potential approaches to tackling this problem and treating patients with RDs in a quality and effective manner is to form an RD ecosystem. This represents a functional environment that integrates all stakeholders, procedures, and relationships required for the coordinated and effective treatment of patients. This paper explores the current situation in the field of RDs, especially in light of the proposed ecosystemic arrangement, and provides an outline for the design of an RD ecosystem in Slovenia. The research applies a case-study design, where focus groups are used to collect evidence from the field, assess the state of affairs, and generate ideas. Structured focus group discussions were conducted with preeminent experts affiliated with the leading institutions in the field of RDs in Slovenia. Analyses and interpretations of the obtained data were carried out by means of conventional content analysis. Setting up an RD ecosystem in Slovenia would lead to significant benefits for patients, as it could promote the coordination of healthcare treatment and facilitate extensive monitoring of the treatment parameters and outcomes. A well-organized RD ecosystem could garner considerable systemic benefits for evidence-informed policymaking, a better utilization of resources, and technological innovation. Delivering quality healthcare in this complex field is largely reliant on the effective integration and collaboration of all entities within the RD ecosystem, the alignment of related systemic factors, and the direction of healthcare services to support the needs and well-being of patients with RDs.

Background: Inborn errors of metabolism (IEM) are disorders with a block in the metabolic pathway caused by a genetic defect of a specific enzyme. Although each of these diseases is quite rare, as a group they account for a significant proportion of newborn and childhood morbidity and mortality. Early diagnosis is important to prevent complications or even death of the child. Selective screening is an important diagnostic tool for the diagnosis of IEM. Methods: In Slovenia, symptomatic patients with suspected IEM are referred to the University Children's Hospital Ljubljana. Techniques used for selective screening are gas chromatography-mass spectrometry, ion exchange chromatography-post-column derivatization, liquid chromatography-tandem mass spectrometry and isoelectric focusing. Fluorimetric method is used for enzyme activity measurement. Results: There are 168 patients with amino and organic acidemias, 5 patients with disorders in fatty acids metabolism, 1 patient with a congenital disorder of glycosylation, 42 patients with Fabry disease (of which 37 are adult) and 20 patients with Gaucher disease (of which 18 are adult) in the Slovenian Register for Rare Diseases. Conclusions: In Slovenia, management of patients with IEM is centralized at the University Children's Hospital, with the exception of adult patients with Fabry and Gaucher disease. The team work is well organized with close cooperation between the laboratory and pediatricians specialized in metabolic disorders. According to the known frequencies of IEM from the literature, we would expect more positive results than obtained. To evaluate these results, we are planning to perform a pilot study on expanded newborn screening.

Fenilketonurija (PKU) je avtosomnorecesivno dedna bolezen zaradi nezadostne aktivnosti encima fenilalaninska hidroksilaza (PAH), ki katalizira pretvorbo fenilalanina (Phe) v tirozin, pri čemer kot kofaktor uporablja tetrahidrobiopterin (BH4). Pojavnost PKU v populacijah kavkaške rase je okrog 1/10.000. Gen PAH se nahaja na 12. kromosomu in ga sestavlja 13 eksonov. Opisanih je nad 600 mutacij gena PAH, ki povzročajo različne stopnje pomanjkanja katalitske aktivnosti PAH. Zaradi tega je povišana vrednost Phe v krvi (hiperfenilalaninemija % HFA) povezana, če se ne zdravi, s poškodbo osrednjega živčevja, ki se kaže z duševno zaostalostjo. Klasifikacija PKU temelji na presnovnem fenotipu bolnika (glede na stopnjo HFA); razlikujemo tri podvrste PKU (klasična, zmerna in blaga) ter blago HFA, ki je ločena klinična entiteta. Pojavnost klasične PKU v Sloveniji smo ocenili na približno 1/10.000, pogostost prenašalcev klasične PKU v splošni populaciji pa na 1/50. Kumulativna pojavnost vseh oblik PKU (klasična, zmerna, blaga PKU) je približno 1/6.000; pojavnost blage HFA pa približno 1/3.500. V preglednem članku smo zajeli tudi prej objavljene rezultate raziskav značilnosti slovenskih bolnikov s PKU, ki so bile na Kliničnem oddelku za endokrinologijo, diabetes in presnovne bolezni Pediatrične klinike Ljubljana opravljene v letih 2008%2012. Naša populacija bolnikov s PKU je po genetskih značilnostih primerljiva z opisanimi okoliškimi populacijami, vključuje pa pet novih, doslej neopisanih mutacij gena PAH. Presejanje vseh novorojencev na PKU se v Sloveniji izvaja od leta 1979. Vzročnega zdravljenja PKU ne poznamo, potrebna pa je čimprejšnja uvedba dietnega zdravljenja z omejitvijo vnosa Phe; zdravljenje s BH4 pri odzivnih bolnikih poveča toleranco za Phe.

Acute hyperammonaemia is a consequence of inborn defects of urea cycle or acute liver damage. Clinical presentation varies considerably with the age of the aff ected individual and includes nausea, vomiting, neuropsychiatric symptoms, convulsions and progressive lethargy with a deepening coma. Ammonia concentration above 200 microM is a medical emergency and requires prompt treatment, regardless of its aetiology. The acute management includes restriction of protein intake, glucose infusion suffi cient to maintain anabolic state, administration of ammonia scavengers (sodium benzoate, sodium phenylacetate, sodium phenylbutyrate), administration of urea cycle substratesand haemodialysis when the concentration of ammonia is exceedingly high or does not respond promptly to the medical treatment. Elevated ammonia concentration is neurotoxic and causes irreversible glial and neuronal damage resulting in cerebral oedema with poor outcome. Early diagnosis and prompt treatment are crucial and may considerably improve the clinical course.

Background. Cardiovascular diseases represent the most frequent cause of morbidity and mortality in developed countries. Blood cholesterol concentration inffluences the progression of atherosclerosis and most developed countries started programs for early detection of hypercholesterolemia. The study presents data analysis related to the total cholesterol concentrations obtained from 5-year old children. Additionally, guidelines for improving the follow-up work with children having hypercholesterolemia are presented. Methods. Values of total cholesterol concentration of 2742 children born 1995 or 1996 were obtained from 17 pediatric primary care facilities in Slovenia. Data analysis included values of body mass index (BMI). The study was approved by the State Committee for Medical Ethics (103/02/02). Results. Values of total cholesterol concentrationwere not distributed according to the normal distribution. Total cholesterol concentration was significantly higher in girls (median 4.41 mmol/L, 5th percentile 3.3 mmol/l and 95th percentile 5.8 mmol/L) compared to boys (median 4.3 mmol/L, 5th percentile 3.2 mmol/l and 95th percentile 5.6 mmol/L) (p < 0.0001). Twenty-one percent of values were above 5 mmol/L, 15% above 5.2 mmol/L and 2.8% above 6 mmol/L. Total cholesterol concentration did not correlate with the BMl. (Abstract truncated at 2000 characters). Izhodišča. Bolezni srca in ožilja predstavljajo v razvitem svetu najpogostejšivzrok zbolevnosti in smrtnosti. Razvoj ateroskleroze, ki je vzroktem boleznim, je močno odvisen od koncentracije holesterola v krvi. Večina razvitih držav zato uvaja zgodnje presejalno testiranje za odkrivanje hiperholesterolemije. V naši raziskavi smo analizirali podatke, dobljene pri slovenskem presejalnem testiranju petletnih otrok ob sistematskem pregledu in na podlagi naših in tujih izkušenj izoblikovali smernice za obravnavo otrok inmladostnikov s hiperholesterolemijo. Metode. Analizirali smo vrednosti koncentracije celokupnega holesterola 2742 naključno izbranih 5-letnih otrok, rojenih leta 1995 in 1996, iz 17 pediatričnih dispanzerjev po Sloveniji. V statistično analizo je bil zajet tudi indeks telesne mase (ITM). Raziskavo je odobrila Komisija za medicinsko etiko (103/02/02). Rezultati. Vrednosti koncentracije celokupnega holesterola niso razporejene skladno z normalno razporeditvijo. Koncentracija celokupnega holesterola je značilno višja pri deklicah (mediana 4,41 mmol/L, 5 percentila 3,,3 mmol/l, 95 percentila 5,8 mmol/L) kot pri dečkih (mediana 4,3 mmol/L, 5 percentila 3,2 mmol/l, 95 percentila 5, 6 mmol/L) (p < 0,0001). Enaindvajset odstotkov vrednosti je nad 5 mmol/L, 15 % nad 5,2 mmol/L in 2,8% nad 6 mmol/L. Vrednosti koncentracije celokupnega holesterola ne korelirajo z vrednostmi ITM. (Izvleček skrajšan pri2000 znakih).

Background. Graves disease is the most common cause of hyperthyrosis in children and adolescents. The optimal treatment for children with AH remains controversial. The patients are usually treated with antithyroid drugs in combination with thyroxine, followed by definitive treatment with either surgery or radio-iodine if stable remission with antithyroid drug can not be achieved. Patients and methods. Between 1991 and 2000, 45 children (41 girls) from 0.5 to 17.5 years were treated at the University Childrens' Hospital Ljubljana. Results and conclusions. Fourteen (31.1%) patients achieved long-term remission with antithyroid drugs alone. 12 (26.7%) of children needed further therapy. Surgery was carried out in 6 (50%), ablation therapy with J131 was successfully used in other six patients. Izhodišča. Avtoimuna hipertiroza (AH) je najpogostejši vzrok hipertiroze pri otrocih in mladostnikih. Diagnoza bolezni je hitra in zanesljiva, če le pomislimo nanjo. Bolezen poteka s pogostimi relapsi in recidivi. Mnenja o optimalnem načinu zdravljenja se še vedno razhajajo. Po navadi pričnemo zdravljenje s tirostatiki z ali brez dodatka tiroksina, ob neuspehu pa nadaljujemo s kirurškim zdravljenjem ali radioterapijo z 131J. Pacienti in metode. V zadnjih desetih letih se je na Kliničnem oddelku za endokrinologijo,diabetes in presnovne bolezni PeK v Ljubljani zaradi AH zdravilo 45 otrok (41 deklic), starih od 0,5-17,5 leta. Rezultati in zaključki. Trajno remisijo je po uvedbi medikamentoznega zdravljenja doseglo 14 (31,1%) otrok. Po enem ali več relapsih je evtirotično stanje doseglo 18 (40%) otrok, le eden (2,2%) ni dosegel remisije in še prejema terapijo z metimazolom in tiroksinom. Dvanajst (26,7%) otrok je zaradi nedosežene remisije potrebovalo dodatno zdravljenje, pri šestih otrocih (50%) je bila ščitnica odstranjena operativno, 6(50%) pa jih je prejelo zdravljenje z 131J.

Uvod: Prader-Willijev sindrom je redka genetska bolezen, za katero je značilna motnja v hipotalamo-hipofizni osi. V obdobju novorojenčka je prisotna centralna hipotonija in težave z nezadostnim hranjenjem. Po 2. letu starosti se telesna masa začne povečevati, pojavi se hiperfagija, ki brez nadzora vodi v debelost. Bolezen poleg posameznika močno prizadene tudi celotno družino in starši pogosto ne prejmejo zadostne podpore. Namen: Z diplomsko nalogo smo želeli predstaviti Prader-Willijev sindrom in raziskati izkušnje staršev glede opore, ki so jo prejeli s strani zdravstvenih delavcev v obdobju dojenčka. Ugotoviti želimo tudi, kakšna je vloga babice v primeru rojstva otroka z omenjenim sindromom. Metode dela: V prvem delu je bila uporabljena deskriptivna metoda dela s pregledom strokovne in znanstvene literature. V drugem empiričnem delu smo uporabili kvantitativno metodo dela in izdelali spletni anketni vprašalnik, ki smo ga posredovali staršem otrok s Prader-Willijevim sindromom. Rezultati so bili obdelani s kvantitativno analizo. Rezultati: Ugotovili smo, da se starši v večini niso mogli opredeliti ali so bili zadovoljni s čustveno oporo, informacijami o stanju otroka in empatijo babice v porodni sobi, v primeru, da je bil otrok takoj po porodu sprejet na intenzivno nego. Kožni stik z otrokom na intenzivni negi je bil omogočen več kot četrtini vprašanih staršev. Vsem mamam pa je bila omogočena možnost obiskov na intenzivni negi in črpanje mleka. Na splošno so izkušnje staršev s podporo zdravstvenih delavcev v obdobju dojenčka in ob postavitvi diagnoze dobre. Starši so navedli primanjkljaj na področju znanja in izkušenj zdravstvenih delavcev in pomanjkanje literature o sindromu v slovenščini. Z raziskavo smo dokazali, da so bili starši, ki so diagnozo prejeli bolj zgodaj bolj zadovoljni z oporo zdravstvenih delavcev. Razprava in zaključek: Zgodnje izkušnje staršev s podporo imajo lahko velik vpliv na sprejemanje bolezni v prihodnosti. Babice bi že takoj po porodu morale več pozornosti nameniti čustveni opori, empatiji, zagotavljanju informacij in kožnemu stiku. Več truda bi bilo potrebno vložiti v zagotavljanje literature glede sindroma v slovenskem jeziku. Zdravstveni delavci bi se morali bolje zavedati specifičnosti soočanja z redko boleznijo in skrbeti tudi za vseživljenjsko učenje. Pomembno je, da pacienta in družino usmerimo k verodostojnemu viru informacij. Introduction: Prader-Willi syndrome is a rare genetic disease characterized by a disorder of the hypothalamic-pituitary axis. During the neonatal period, central hypotonia and malnutrition problems are present. After the age of 2, body weight begins to increase, hyperphagia occurs, which without supervision leads to obesity. The disease severely affects not only the patient but the whole family and parents often do not receive sufficient support. Purpose: With this thesis, we wanted to present Prader-Willi syndrome and explore the experiences of parents regarding support they received from healthcare workers during infancy. We also want to find out what is the role of a midwife in case of the birth of a child with the mentioned syndrome. Methods: In the first part, a descriptive method of work with a review of professional and scientific literature was used. In the second, empirical part, we used a quantitative method of work and created an online survey questionnaire, which we forwarded to parents of children with Prader-Willi syndrome. The results were processed by quantitative analysis. Results: We found that most parents could not declare whether they were satisfied or not with the emotional support, information about the child's condition and the midwife’s empathy in the delivery room in case their child was admitted to intensive care immediately after birth. Skin contact with a child in intensive care was provided to more than a quarter of the parents surveyed. All mothers were allowed to visit their child in intensive care and pump milk. Overall, parents experience regarding healthcare workers support during infancy and at diagnosis is good. Parents pointed out a gap in the knowledge and experience of healthcare workers and a lack of literature on the syndrome in the Slovenian language. The study showed that parents who had received the diagnosis earlier were more satisfied with the support of healthcare workers. Discussion and conclusion: Early support provided to parents can have a major impact on future acceptance of illness. Midwives should pay more attention to emotional support, empathy, information provision, and skin contact immediately after birth. More effort should be invested in providing literature on the syndrome in the Slovenian language. Healthcare workers should be better aware of the specifics of dealing with a rare disease and also provide lifelong learning. It is important to guide the patient and his family to a credible source of information.

Introduction. Developmental delay and dysmorphic features affect 1 - 3 % of paediatric population. In the last few years molecular cytogenetic high resolution techniques (comparative genomic hybridization arrays and single-nucleotide polymorphism arrays) have been proven to be a first-tier choice for clinical diagnostics of developmental delay and dysmorphic features. Methods and results. In the present article we describe the clinical advantages of molecular cytogenetic approach (comparative genomic hybridization arrays and single nucleotide polymorphism arrays) in the diagnostic procedure of two children with developmental delay, dysmorphic features and additional morphological phenotypes. Additionally, we demonstrate the necessity of fluorescent in situ hybridization utilisation to identify the localisation and underlying mechanism of detected chromosomal rearrangement. Conclusions. Two types of chromosomal abnormalities were identified and confirmed using different molecular genetic approaches. Comparative genomic hybridization arrays and single nucleotide polymorphism arrays are hereby presented as important methods to identify chromosomal imbalances in patients with developmental delay and dysmorphic features. We emphasize the importance of molecular genetic testing in patients’ parents for the demonstration of the origin and clinical importance of the aberrations prior determined in the patients. The results obtained using molecular cytogenetic high resolution techniques methods are the cornerstone for proper genetic counselling to the affected families.