Epidemiological and Clinical Study of Rett Syndrome in population of Serbia

Retov sindrom (RTT) je teţak neurorazvojni poremećaj koji se uglavnom susreće kod osoba ţenskog pola. U različitim delovima sveta RTT ima prevalenciju od 0,4-2,23:10000 devojčica. Kod većine bolesnika nastaje usled mutacija MECP2 gena. Ciljevi rada: ispitavanje epidemioloških i kliničkih karakteristika RTT u populaciji Srbije; ispitivanje genotipsko-fenotipske korelacije u našoj sredini, te prognostičkog značaja odabranih demografskih, kliničkih i genetičkih varijabli; ispitivanje depresivnosti i kvaliteta ţivota majki koje se staraju o deci sa RTT. Materijal i metode: Studija je obuhvatila 102 bolesnice kod kojih je RTT dijagnostikovan izmeĎu 1987. i 2011. godine. Za utvrĎivanje epidemioloških parametara (incidencije i prevalencije) korišćeni su podaci o vitalnoj statistici Republičkog zavoda za statistiku Srbije. Korišćena je medicinska dokumentacija Instituta za zdravstvenu zaštitu majke i deteta Srbije i rezultati molekularnih analiza učinjenih u laboratoriji Biološkog fakulteta u Beogradu. Za analizu rezultata korišćene su deskriptivne i analitičke statističke metode. Rezultati: Incidencija RTT u Srbiji iznosi 0,586:10000 ţivoroĎene ţenske dece. Većina bolesnica (86%) ima klasični oblik RTT. Najčešće mutacije u MECP2 genu u populaciji bolesnica sa RTT u Srbiji su T158M, R255X i R168X. Epilepsija je prisutna kod 70,5% obolelih u ispitivanoj grupi. Prema rezultatima Kaplan-Meierove funkcije preţivljavanja, bolesnice sa RTT u Srbiji imaju veći rizik za rani smrtni ishod nego što pokazuju studije iz razvijenih sredina. Najčešći uzrok smrti ovih bolesnica u Srbiji bila je pneumonija. Klinički skor teţine bolesti (Clinical Severity Score, CSS) je bio najsnaţniji prediktor smrtnog ishoda kod RTT. Pokazana je visoka prevalencija teške depresije od 30,6% meĎu majkama koje se staraju o deci sa RTT. Zaključak: Incidencija RTT u Srbiji odgovara nalazima velikih studija iz drugih zemalja. Postoji genotipsko-fenotipska korelacija za više kliničkih aspekata RTT. PotvrĎena je vrednost skora CSS u proceni teţine stanja i predikciji smrtnog ishoda. Neophodno je planirati psihosocijalne interventne mere u porodicama obolelih zbog visoke prevalencije depresije meĎu majkama dece sa RTT.Introduction: Rett Syndrome (RTT) is severe neurodevelopmental disorder which mainly affects females. Prevalence of RTT ranges from 0,4-2,23:10000 girls in different populations worldwide. Majority of cases are caused by mutations in MECP2 gene. Objectives: investigation of epidemiological and clinical features of RTT in population of Serbia; investigation of genotype-phenotype correlation and evaluation of prognostic value of selected demographic, clinical and genetic factors; investigation of depression and health-related quality of life in mothers giving care to children with RTT. Matherial and methods: Study included 102 female patients with RTT diagnosed between 1987. and 2011. Estimation of epidemiological parameters (incidence i prevalence) was based on vital statistics provided by Statistical Office of the Republic of Serbia. Medical documentation of Mother and Child Health Institute of Serbia was used, as well as genetic diagnosis reports from Biological Faculty in Belgrade. Data analysis included descriptive and analytical statistical methods. Results: Incidence of RTT in Serbia is estimated at 0,586:10000 live female births. Majority of patients (86%) have classical type of RTT. Most common mutations in Serbian population with RTT were T158M, R255X and R168X. Epilepsy was present in 70,5% of our group. According to Kaplan-Meier survival analysis, Serbian RTT patients had higher risk for earlier mortality than shown in studies from developed countries. Pneumonia was the most frequent cause of death in our RTT group. Clinical Severity Score (CSS) was the strongest single predictor of lethal outcome in RTT patients. High prevalence of severe depression (30,6%) was noted in mothers giving care to children with RTT. Conclusion: Incidence of RTT in Serbia corresponds to findings of major epidemiological studies. The genotype-phenotype correlation is present regarding certain clinical aspects of RTT. Value of CSS in evaluating severity of the RTT and predicting fatal outcome was reconfirmed. There is a necessity of psychosocial interventional measures directed at families with RTT children due to high prevalence of depression in care giving mothers

Procena zdravstvenog stanja i kvaliteta života beskućnika u Beogradu

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 disease 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 lt 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 lt 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.Uvod/Cilj. Beskućništvo predstavlja problem sa širokim društvenim, zdravstvenim i ostalim implikacijama. Postoje brojni dokazi da beskućnici imaju višu prevalenciju hroničnih (mentalnih i somatskih) oboljenja u odnosu na opštu populaciju. Cilj rada je bio utvrđivanje kvaliteta života (KŽ) i depresivnosti kod beskućnika, socijalnodemografskog i zdravstvenog statusa u ovoj populaciji, te analiza faktora koji utiču na KŽ i depresivnost beskućnika. Metode. Istraživanje je sprovedeno u Centru za smeštaj odraslih i starih lica u Beogradu tokom januara 2012. godine. Korišćen je komplet upitnika: SF-36 za ispitivanje KŽ, Bekova skala depresije II (BDI-II) i sociodemografski upitnik. Analiza je obavljena metodama deskriptivne i analitičke statistike. Rezultati. Studija je obuhvatila 104 ispitanika. Većinu su činili muškarci (74%), a prosečna starost je iznosila 48,2 ± 13,0 godina. Kod 35,6% ispitanika utvrđena je dijagnoza psihijatrijske bolesti (najčešće depresije). Samoubistvo je pokušalo 28 (26,9%) ispitanika. U uzorku je bilo 82,7% pušača, a najčešće hronične somatske bolesti su bile kardiovaskularne bolesti. Komorbiditet više somatskih bolesti je bio prisutan kod trećine ispitanika. Fizička uloga je jedini domen KŽ koji je bio niži nego u opštoj populaciji (p lt 0,001). Depresija teškog stepena utvrđena je kod 20,2% ispitanika. Negativna korelacija postojala je između skorova BDI-II i svih skorova KŽ (p lt 0,001). Zaključak. Mere za prevenciju beskućništva bi trebalo da uključe formiranje nacionalnog registra beskućnika, razvoj sistemske međusektorske saradnje i primenu specijalnih psihosocijalnih interventnih strategija. Kod beskućnika zdravstveni sistem treba da bude fokusiran na prevenciju i lečenje mentalnih poremećaja i hroničnih somatskih oboljenja

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

Altres ajuts: The financial support for carrying out this work was received from Fundació Parc Taulí- Institut d'Investigació i Innovació Parc Taulí I3PT (CIR2015/040), Asociación Española de Síndrome de Angelman [...].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. 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. 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

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

Chronic kidney disease in TARS2-related mitochondrial disease – A case report

This case report describes a patient harboring TARS2 mutations where chronic kidney disease stands out as the predominant clinical feature. The distinct manifestation observed in this case underscores the importance of continual exploration and documentation of diverse clinical presentations associated with TARS2 mutations, contributing to an enriched comprehension of the spectrum of effects linked to this genetic variatio

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) lt 1500/mm(3) was present in all 33 patients, with severe neutropenia (ANC lt 500/mm(3)) 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 gt A/c.785G gt A and c.81T gt A/c.1042_1043delCT are associated with earlier onset of neutropenia. Patients carrying c.785G gt 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

Use of mechanical ventilation in pediatric patients

Background/Aim. Major aims of mechanical ventilation (MV) in pediatrics mean the contribution to complete recovery of acute disorder or to establishing stability of previously long-term changed health condition. MV is used today in 16-46% of patients treated in pediatric intensive care units. The aim of this paper was to get insight into the presence of the disease and pathologic conditions and outcome of MV regarding previous health condition of pediatric patients. Methods. This retrospective study included 476 pediatric patients (beyond neonatal age) who underwent mechanical ventilation (MV). On the basis of previous health status the patients were classified in two groups: the group A consisted of 157 children with no previous chronic disease leading to MV and the group H comprised of 319 children who received MV due to worsening of previous chronic disease. Results. In both groups of pediatric patients there was significant predominance of younger age patients. Acute and chronic neurological disorders were the most frequent conditions requiring use of MV. Out of a total number (476) of the patients, 178 patients (37.4%) died. In the group A 17 patients (10.9%) died, while in the group H mortality rate was significantly higher (161 or 50.5% patients died; p < 0.01; RR 4.85; CI 3.1-7.6). Total duration time of MV in all the patients was 7 525 days, with 1 345 days (15%) accounted for the group A and 4 567 days (85%) for the group H. Mean MV duration was 7.48 (± 9.23) days for the patients in the group A which is significantly shorter in comparison to mean 21.8 (± 57.96) days for the group H patients (p < 0.001). Conclusion. These results point out significant contribution of MV to better outcome in pediatric patients with different acute disorders. Clear dominance of chronically ill children requiring mechanical ventilation due to acute worsening of their condition implies new complexity of problems regarding organization of pediatric intensive care and treatment