DNA polymerase-α regulates the activation of type I interferons through cytosolic RNA:DNA synthesis.

Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations that disrupt nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts the expression of POLA1, which encodes the catalytic subunit of DNA polymerase-α. Unexpectedly, POLA1 deficiency resulted in increased production of type I interferons. This enzyme is necessary for the synthesis of RNA:DNA primers during DNA replication and, strikingly, we found that POLA1 is also required for the synthesis of cytosolic RNA:DNA, which directly modulates interferon activation. Together this work identifies POLA1 as a critical regulator of the type I interferon response.

Clinical and genetic characteristics of patients with congenital hyperinsulinism in 21 non-consanguineous families from Serbia.

Persistent hypoglycaemia in newborns and infants is most commonly caused by congenital hyperinsulinism (CHI). Most CHI studies report outcomes in children from both consanguineous and non-consanguineous families which can affect the phenotype-genotype analysis. The aim of this study was to analyze characteristics of patients with CHI in 21 non-consanguineous families from Serbia. This retrospective cohort study included a total of 21 patients with CHI treated in the Mother and Child Healthcare Institute of Serbia during the past 20 years. The prevalence of macrosomia at birth was very low in our cohort (4.8%). Median age at presentation was 6 days, with seizures as the presenting symptom in 76% of patients. Only four patients (19%) were diazoxide unresponsive, and eventually underwent pancreatectomy. Genetic testing was performed in 15 patients and genetic diagnosis was confirmed in 60%, with all patients being heterozygous for detected mutations. The ABCC8 gene mutations were detected in 55.6%, GLUD1 in three patients (33.3%) with HIHA syndrome and one patient had HNF4A gene mutation and unusual prolonged hyperglycaemia lasting 6 days after diazoxide cessation. Neurodevelopmental deficits persisted in 33% of patients.Conclusion: This is the first study regarding CHI patients in Serbia. It suggests that in countries with low consanguinity rate, majority of CHI patients are diazoxide responsive. The most common mutations were heterozygous ABCC8, followed by GLUD1 and HNF4A mutations, suggesting the potential benefit of population-tailored genetic analysis approach, targeting the mutations causing CHI via dominant inheritance model in regions with low consanguinity rates. What is Known: • Persistent hypoglycaemia during infancy and early childhood is most commonly caused by congenital hyperinsulinism (CHI). • Consanguinity is a very important factor regarding the genetics and phenotype of CHI, increasing the risk of autosomal recessive genetic disorders, including the severe, diazoxide-unresponsive forms caused by recessive inactivating mutations in ABCC8 and KCNJ11. What is New: • Results of the present study which included CHI patients from 21 non-consanguineous families suggest that in countries with low consanguinity rates, majority of CHI patients can be diazoxide responsive, with most common mutations being heterozygous ABCC8, followed by GLUD1 and HNF4A mutations. • Unusually prolonged hyperglycaemic reaction to diazoxide treatment in a patient with HNF4A mutation was also described in the present study.

Appendiceal involvement in a patient with Gaucher disease.

Almost any anatomical compartment may be involved in Gaucher disease (GD). Abdominal lymphadenopathy occurred during enzyme replacement therapy in more than a dozen children with GD so far. A fourteen-year-old boy from Serbia developed clinical signs of acute appendicitis six years after the onset of GD type 3 related abdominal lymphadenopathy. Ultrasound examination showed diffuse thickening of the intestinal wall in the ileocoecal region with periappendicular infiltration. An appendectomy was performed four months after conservative treatment with antibiotics. Histopathology revealed macrophages with cytological characteristics of Gaucher cells densely crammed in mesoappendiceal adipose tissue. Also the multifocal replacement of subserosal tissue by Gaucher cells and their infiltration to a variable depth of muscularis propria of the appendix were verified. Frank infiltration of the vermiform appendix with Gaucher cells represents a novel observation in a wide spectrum of manifestations reported in GD. A possible causative relationship of this infiltration with appendicitis is considered.

Novel intragenic deletions within the UBE3A gene in two unrelated patients with Angelman syndrome: case report and review of the literature.

BACKGROUND: Patients with Angelman syndrome (AS) are affected by severe intellectual disability with absence of speech, distinctive dysmorphic craniofacial features, ataxia and a characteristic behavioral phenotype. AS is caused by the lack of expression in neurons of the UBE3A gene, which is located in the 15q11.2-q13 imprinted region. Functional loss of UBE3A is due to 15q11.2-q13 deletion, mutations in the UBE3A gene, paternal uniparental disomy and genomic imprinting defects. CASE PRESENTATION: We report here two patients with clinical features of AS referred to our hospital for clinical follow-up and genetic diagnosis. Methylation Specific-Multiplex Ligation-Dependent Probe Amplification (MS-MLPA) of the 15q11.2-q13 region was carried out in our laboratory as the first diagnostic tool detecting two novel UBE3A intragenic deletions. Subsequently, the MLPA P336-A2 kit was used to confirm and determine the size of the UBE3A deletion in the two patients. A review of the clinical features of previously reported patients with whole UBE3A gene or partial intragenic deletions is presented here together with these two new patients. CONCLUSION: Although rare, UBE3A intragenic deletions may represent a small fraction of AS patients without a genetic diagnosis. Testing for UBE3A intragenic exonic deletions should be performed in those AS patients with a normal methylation pattern and no mutations in the UBE3A gene.

Epidemiology of Rett syndrome in Serbia: prevalence, incidence and survival.

BACKGROUND: Rett syndrome (RTT) is a severe neurodevelopmental disorder that represents the second most common cause of mental retardation in females. However, incidence and prevalence of RTT are scarcely reported. METHODS: A retrospective study included all patients with RTT diagnosed between 1981 and 2012 in Serbia. Estimation of incidence and prevalence was calculated on the basis of vital statistics reported by Statistical Office of Republic of Serbia. RESULTS: From 1981 to 2012, RTT has been diagnosed in 102 girls in Serbia. Incidence of RTT in Serbia is estimated at 0.586:10,000 female live births. We estimated the prevalence of RTT in population of females younger than 19 years at 1:8,439. Death occurred in 19 patients (18.63%), with pneumonia as the most common cause. The lethal outcome by the age of 12 years could be expected for 11% of patients. The mean age at diagnosis was 3.5 years and we have confirmed a significant trend towards earlier dianosis during studied period. CONCLUSIONS: Rett syndrome incidence in Serbia is in accordance with reports from other countries. Serbian RTT patients have increased risk for early death when compared to patients in more developed countries, most commonly due to pneumonia. There was significant trend towards early diagnosis of RTT in Serbia over recent decades.

Reverse Phenotyping after Whole-Exome Sequencing in Children with Developmental Delay/Intellectual Disability-An Exception or a Necessity?

This study delves into the diagnostic yield of whole-exome sequencing (WES) in pediatric patients presenting with developmental delay/intellectual disability (DD/ID), while also exploring the utility of Reverse Phenotyping (RP) in refining diagnoses. A cohort of 100 pediatric patients underwent WES, yielding a diagnosis in 66% of cases. Notably, RP played a significant role in cases with negative prior genetic testing, underscoring its significance in complex diagnostic scenarios. The study revealed a spectrum of genetic conditions contributing to DD/ID, illustrating the heterogeneity of etiological factors. Despite challenges, WES demonstrated effectiveness, particularly in cases with metabolic abnormalities. Reverse phenotyping was indicated in half of the patients with positive WES findings. Neural network models exhibited moderate-to-exceptional predictive abilities for aiding in patient selection for WES and RP. These findings emphasize the importance of employing comprehensive genetic approaches and RP in unraveling the genetic underpinnings of DD/ID, thereby facilitating personalized management and genetic counseling for affected individuals and families. This research contributes insights into the genetic landscape of DD/ID, enhancing our understanding and guiding clinical practice in this particular field of clinical genetics.

Age-specific causes of upper gastrointestinal bleeding in children.

The etiology of upper gastrointestinal bleeding (UGIB) varies by age, from newborns to adolescents, with some of the causes overlapping between age groups. While particular causes such as vitamin K deficiency and cow's milk protein allergy are limited to specific age groups, occurring only in neonates and infants, others such as erosive esophagitis and gastritis may be identified at all ages. Furthermore, the incidence of UGIB is variable throughout the world and in different hospital settings. In North America and Europe, most UGIBs are non-variceal, associated with erosive esophagitis, gastritis, and gastric and duodenal ulcers. In recent years, the most common causes in some Middle Eastern and Far Eastern countries are becoming similar to those in Western countries. However, variceal bleeding still predominates in certain parts of the world, especially in South Asia. The most severe hemorrhage arises from variceal bleeding, peptic ulceration, and disseminated intravascular coagulation. Hematemesis is a credible indicator of a UGI source of bleeding in the majority of patients. Being familiar with the most likely UGIB causes in specific ages and geographic areas is especially important for adequate orientation in clinical settings, the use of proper diagnostic tests, and rapid initiation of the therapy. The fundamental approach to the management of UGIB includes an immediate assessment of severity, detecting possible causes, and providing hemodynamic stability, followed by early endoscopy. Unusual UGIB causes must always be considered when establishing a diagnosis in the pediatric population because some of them are unique to children. Endoscopic techniques are of significant diagnostic value, and combined with medicaments, may be used for the management of acute bleeding. Finally, surgical treatment is reserved for the most severe bleeding.

Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib.

BACKGROUND: Glycogen storage disease type Ib (GSD-Ib) is an inherited metabolic disorder caused by autosomal recessive mutations in SLC37A4 coding for the glucose-6-phosphate transporter. Neutropenia represents major feature of GSD-Ib along with metabolic disturbances. Previous research in GSD-Ib patients did not reveal significant genotype-phenotype correlation. Our objective was to explore the frequency and severity of neutropenia and it's complications in relation to genotype of GSD-Ib patients. METHODS: We estimated cumulative incidence of neutropenia and severe neutropenia, relation of genotype to absolute neutrophil count (ANC), and dynamics of ANC during serious bacterial infections (SBI) in a cohort of Serbian GSD Ib patients. Impact of genotype on GSD Ib-related inflammatory bowel disease (IBD) was also assessed. RESULTS: Absolute neutrophil count (ANC) < 1500/mm3 was present in all 33 patients, with severe neutropenia (ANC<500/mm3) occurring in 60.6% of patients. The median age at neutropenia onset was 24 months, while severe neutropenia developed at median of 4.5 years. The ANC was elevated during 90.5% episodes of SBI. Genotypes c.81T>A/c.785G>A and c.81T>A/c.1042_1043delCT are associated with earlier onset of neutropenia. Patients carrying c.785G>A mutation express a higher capacity for ANC increase during SBI. Inflammatory bowel disease was diagnosed in 8 patients (24.2% of total) with median age of onset at 7 years. Risk for IBD occurrence was not significantly affected by gender, genotype and severity of neutropenia. CONCLUSIONS: We may conclude that certain mutations in SLC37A4 influence the risk for severe neutropenia occurrence but also affect the capacity to increase ANC during SBI.

Postprandial hyperinsulinemic hypoglycemia in a child as a late complication of esophageal reconstruction.

BACKGROUND: Postprandial hyperinsulinemic hypoglycemia (PHH) is an increasingly recognized complication of gastric bypass surgery in obese adults, distinct from the "dumping syndrome". CASE PRESENTATION: Upon birth, primary repair of esophageal atresia was performed, and at the age of 14 months definite esophageal reconstruction was performed. At the age of 3 years, recurrent brief episodes of symptomatic hypoglycemia started. At the age of 5.7 years the girl was admitted to our clinic and investigations indicated hyperinsulinemic hypoglycemia. Oral glucose tolerance test (OGTT) and continuous glucose monitoring results revealed frequent postprandial hypoglycemic events, which were always preceded by early postprandial hyperglycemia. It was concluded that the patient had PHH caused by a delayed and hyperinsulinemic response to carbohydrate intake as a result of esophagogastric surgery. Treatment with acarbose was titrated using flash glucose monitoring, which resulted in satisfactory glucose regulation. CONCLUSIONS: This is the first described case of a child with PHH following esophageal reconstruction.

Early Presentation of Hyperinsulinism/Hyperammonemia Syndrome in Three Serbian Patients.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is considered as the second most common type of hereditary HI. Correlation of genotype and phenotype in HI/HA syndrome has been described in several studies. We present three Serbian patients with HI/HA syndrome with emphasis on a possible correlation between genotype and clinical manifestations. Patient 1 was heterozygous for a de novo mutation p.S445L in the GLUD1 gene, while patients 2 and 3 (son and mother) both carry the p.R221C mutation. Early onset of hypoglycaemia with generalized seizures was recorded in infancy in all three patients. The two male patients had mild developmental delay, while the female patient presented with epilepsy. Analysis of Serbian patients with HI/HA syndrome confirms the association of p.S445L and p.R221C mutations with hypoglycaemic seizures noted within the first three months of life and with subsequent risk for cognitive impairment and/or epilepsy.

Tetrahydrobiopterin deficiency among Serbian patients presenting with hyperphenylalaninemia.

Hyperphenylalaninemia (HPA) [phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficiencies] is rare inborn metabolic disease characterized by elevated phenylalanine level in body fluids. In Serbia, 62 HPA patients have been identified through newborn screening since 1983. However, pterin pattern analysis is not performed. We present a patient initially diagnosed and treated as classical PKU. At 3 years of age, during infection with H1N1 influenza A virus, the patient first developed a neurologic crisis with encephalopathy and dystonic movements. We suspected that the patient is the first case of BH4 deficiency identified in Serbia. Genetic analyses showed that the patient does not have disease-causing variants of the PAH gene and carries a p.Asp136Val mutation in homozygous state in the PTS gene. For patients with treatable rare diseases, like PKU and BH4 deficiencies, correct diagnosis is crucial for the implementation of optimal treatment. If biochemical tests needed for differential diagnosis are not available, our experience emphasizes the necessity of immediate genetic testing after newborn screening.

Assessment of health status and quality of life of homeless persons in Belgrade, Serbia.

BACKGROUND/AIM: Homelessness is a problem with social, medical, economic, political and other implications. Despite a large number of studies, reports about health-related quality of life (HRQoL) of homeless persons remain sparse. There is a summary of consistent evidence that homeless people have higher prevalence of chronic disease (mental and somatic) than general population. The aim of this study was to assess HRQoL and depression in homeless persons in Belgrade, to describe their sociodemographic factors and health status (the presence of chronic mental and somatic diseases and addiction disorders) and analyse impact of sociodemographic factors and health status to HRQoL and depression of homeless persons. METHODS: The study was conducted in the Shelter for Adult and Elderly Persons in Belgrade, from January 1 to January 31, 2012. A set of questionnaires used in survey included Serbian translation of SF-36 questionnaire, Serbian translation of Beck Depression Inventory-II (BDI-II) and sociodemographic questionnaire. Statistical analysis was performed by descriptive and analytic methods. RESULTS: Our study sample consisted of 104 adult participants. The majority of them were male (74%) and the mean age in the sample was 48.2 +/- 13.0 years. We have found that 35.6% participants had lifetime diagnosis of psychiatric disorder, most frequently depression (lifetime prevalence of 15.4% in the study group). The history of suicide attempts was registered in 28 (26.9%) participants. Lifetime illicit drugs use was reported by 12.5%, daily smoking by 82.7% and daily alcohol consumption by 8.7% of the participants. Most common somatic chronic diseases were cardiovascular while chronic lung diseases were the second most frequent. Single chronic disaese was present in 33 (31.7%) of the participants and comorbidity of 2 chronic diseases was present in 20 of them. A statistically significant difference between participants HRQoL SF-36 domain scores and norms of general population was found only for role physical domain (lower in homeless, p < 0.001). ANOVA showed no statistically significant difference in SF-36 HRQoL domain and composite scores between different age groups, nor did marital status, education level, length of homelessness, alcohol use or smoking significantly affect the HRQoL. The mean BDI-II score in the studied population was 19.1 +/- 11.6. Severe depression was registered in 20.2% of the participants, moderate in 23.1%, mild in 19.2% and minimal in 37.5%. A highly significant negative correlation was verified between BDI-II and all domains and composite scores of SF-36 (p < 0.001). CONCLUSION: Measures for prevention of homelessness should include: foundation of national registry of homeless persons, development of systemic multisectorial cooperation and special psychosocial intervention strategies. In homeless population, health care measures should be focused on prevention and treatment of mental health disorders and chronic somatic diseases.

Health-related quality of life and depression in Rett syndrome caregivers.

BACKGROUND/AIM: Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily affecting females with an estimated incidence of 1:10,000-15,000 female births. Currently, there is no specific treatment that halts or reverses the progression of RTT. Therefore, management was mainly symptomatic, focussed on optimising patient's abilities. The aim of this study was to investigate factors influencing health-related quality of life (HRQoL) and depression in mothers who care for children with Rett syndrome (RTT) in Serbia. METHODS: The cross-sectional study was conducted on 49 mothers giving care to females with RTT. Caregivers" HRQoL was assessed by using the SF-36 questionnaire. Clinical severity score (CSS) of RTT patients and Beck Depression Inventory II (BDI -II) scale were used to quantify RTT severity and mothers' depression, respectively. Statistical assessment included descriptive statistics, t-test, Pearson correlation coefficient and multiple logistic regression. RESULTS: The age of mothers ranged from 22 to 55 years and of their affected children from 3 to 29 years. Severe depression was observed in 15 (30.6%) participants. CSS and BDI-II scores correlated negatively with all SF-36 domains and composite scores. Lowest scoring domains of HRQoL in mothers giving care to RTT children were mental health, vitality and role functioning emotional. Multiple linear regression analysis revealed that severity of RTT patients' disability (CSS) and caregivers' age are factors with strongest influence to HRQoL and depression in care giving mothers. CONCLUSION: Mothers giving care to children with RTT are at high risk of severe depression and lower HRQoL scores of domains that reflect mental well-being. Results of this study can help in planning subsequent interventions directed at families dealing with Rett syndrome.

Vitamin D deficiency in Serbian patients with Rett syndrome.

INTRODUCTION: Rett syndrome (RTT) is a severe neurodevelopmental disorder. Bone manifestations of RTT include osteopenia and fractures. Studies addressing serum vitamin D levels in patients with RTT are scarce. GOALS: The goals of this study were (1) to determine the prevalence of vitamin D deficiency in patients with RTT, (2) to compare serum vitamin D levels between patients with RTT and those with other neurological diseases, and (3) to explore the correlation between demographic and clinical characteristics of patients with RTT and vitamin D levels. METHODS: Demographic and clinical characteristics included age, body mass index Z-score, mutation status, clinical severity score, presence of epilepsy, number of antiepileptic drugs, history of fractures, scoliosis, and ambulation ability. Laboratory parameters included serum 25-hydroxyvitamin D [25(OH)D], PTH, calcium, and alkaline phosphatase. RESULTS: The study included 35 patients with RTT and 35 age-matched females with other neurological diseases. The median serum 25(OH)D concentration in the RTT group was 26.25 nmol/L, with values <75 nmol/L in all participants. Severe deficiency (<25 nmol/L) was detected in 17 of 35 (48.6%) patients. The median 25(OH)D concentration was significantly lower in patients with RTT than in control subjects. The risk for fracture by 12 years of age in patients with RTT was 35.3%. An inverse correlation of the 25(OH)D level to age and PTH level was detected. Patients receiving antiepileptic polytherapy had a 3.3 times greater chance for severe vitamin D deficiency than patients receiving monotherapy. CONCLUSION: The prevalence of vitamin D deficiency in patients with RTT is higher than that in patients with other neurological diseases. The high risk for vitamin D deficiency should be accounted for in the strategy of antiepileptic treatment in RTT, especially when polytherapy is considered.

Molecular Genetics and Genotype-Based Estimation of BH4-Responsiveness in Serbian PKU Patients: Spotlight on Phenotypic Implications of p.L48S.

Phenylketonuria (PKU) is caused by mutations in the gene encoding phenylalanine hydroxylase (PAH) enzyme. Here, we report the updated spectrum of PAH mutations in 61 Serbian PKU patients. By using both DGGE/DNA sequencing and PCR-RFLP, we identified 26 disease-causing mutations (detection rate 99%). The most frequent ones were p.L48S (31%), p.R408W (16.4%), p.P281L (6%), p.E390G (5.2%), and p.I306V (5.2%). Homozygosity value indicated high heterogeneity of Serbian population.To overcome possible pitfalls of patients' phenotypic classification, we used two parameters: pretreatment/maximal phenylalanine blood concentration and Phe tolerance. The two phenotypes did not match only for patients with p.L48S. Therefore, we used Mann-Whitney statistical test to compare pretreatment/maximal blood Phe concentration and Phe tolerance detected in patients with p.[L48S];[null] and p.[missense];[null] genotypes. For patients with p.L48S, our results implied that Phe tolerance is a better parameter for phenotypic classification. Also, Fisher's exact test was used to compare p.L48S effect on phenotype of homozygous and functionally hemizygous patients. Our findings showed that effect of p.L48S was altered in functional hemizygotes. Moreover, phenotypic inconsistency found in homozygotes suggested that interallelic complementation and/or additional factors play a role in genotype-phenotype correlation.Since BH4-supplementation therapy is not available in Serbia, we made the first estimation of its potential benefit based on patients' genotypes. In the analyzed cohort, the total frequency of BH4-responsive mutations was 52.6%. Furthermore, we found a significant number of genotypes (26.2% BH4-responsive and 51% probably BH4-responsive) that may respond to BH4 therapy. This led us to a conclusion that BH4-supplementation therapy could bring benefit to Serbian PKU patients.

Pulmonary involvement in siblings with Gaucher disease type III.

INTRODUCTION: Pulmonary involvement has been described in all types of Gaucher disease (GD) but it is considered as relatively rare manifestation. There are reports suggesting that homozygosity for L444P mutation in GBA gene is associated with a substantial risk for developing primary pulmonary disease in GD. CASE REPORT: We reported sisters with pulmonary involvement in GD type III. Respiratory failure with fatal outcome at 3 years and 4 months of age occurred in K.K. due to pulmonary complications of GD. At the time enzyme replacement therapy (ERT) was not available in Serbia. J.K., homozygous for L444P mutation, developed asymptomatic pulmonary involvement at the age of 6 after 2.5 years of ERT. Pulmonary disease in J.K. was verified by high resolution computerized tomography, cytology of bronchoalveolar lavage fluid and histopathology of transbronchial lung biopsy. CONCLUSION: Primary lung disease in children homoallelic for L444P mutation in GBA gene emerges as a significant clinical manifestation of GD with unclear response to ERT.

Clinical characteristics of respiratory syncytial virus infection in neonates and young infants.

INTRODUCTION/AIM: Infection with respiratory syncytial virus (RSV) occurs during the first year of life in 50% of children and 20%-40% of them have signs of lower respiratory tract infection (bronchiolitis or pneumonia). There is an increased risk for complicated course and death from RSV infection in premature infants, especially those with bronchopulmonary dysplasia (BPD) or congenital heart disease. The aim of our study was to analyze clinical characteristics of laboratory confirmed RSV infection in order to evaluate the need for preventive measures in neonates and young infants. METHODS: The prospective study included children under age of 12 months admitted to our hospital in the period November 2008-March 2009 who were positive for RSV by enzyme immunoassay membrane test. The course of disease was assessed by clinical score and radiographic findings. RESULTS: Infection with RSV was confirmed in 91 patients: 21 (23.0%) were under the age of 30 days, 37 (40.7%) were between 31-60 days, and 33 patients (36.3%) were older than 60 days (p > 0.05). The highest hospitalization rate was in January--33 patients (36.3%; p < 0.01). Disease severity score in these age groups (AG) were: 8.4 +/- 0.4 (AG 0-30 days); 9.0 +/- 0.3 (AG 31-60 days) and 8.3 +/- 0.3 (AG > 60 days), without statistically significant difference among the groups (p > 0.05). Clinical scores in patients with and without risk factors were 10.5 +/- 0.5 and 8.3 +/- 0.2, respectively (p < 0.01). Pathological radiographic findings were observed in 72 (79.1%) and complications (apnea, significant atelectasis, encephalopathy) occured in 15 (16.5%) patients. The average length of hospital stay in complicated and uncomplicated course of the disease was 9 days and 6 days, respectively (p < 0.01). Therapy in 85 (93.4%) patients included bronchodilators, while systemic glucocorticoids and oxygen therapy were used in 51 (56.0%) and 44 (48.4%) patients, respectively. Death occured in 2 (2.2%) patients, both from a high risk group (the patient with BPD and the other one with congenital heart disease and Down syndrome). CONCLUSION: Infection with RSV in our settings showed marked seasonal characteristics with highest hospitalization rate in January. Although the course and outcome of the disease were favorable in the majority of our patients, the need for hospitalization and administration of therapy with possible side effects warrants that general measures for prevention of respiratory infections are followed especially in the first year of life. Severe disease and death are more probable in neonates and infants with risk factors. In these children passive immunisation with specific monoclonal antibody (e.g. palivizumab) during RSV season should be considered.