Quality of Life of Elementary School Students with Type 1 Diabetes in a Developing Country during the COVID Pandemic.

Type 1 diabetes (T1D) is a condition that affects all aspects of life, and thus is closely related to the quality of life itself. Dealing with it during the COVID-19 pandemic is a big challenge. A case-control study conducted in Montenegro at the end of 2021 included 87 elementary school students with T1D and 248 of their peers as controls matched by gender. Standardized questionnaires were distributed to participants (Peds-QL Generic core 4.0 questionnaire for all participants and Peds-QL Diabetes Module 3.2 only for cases). Based on them, the results of obtained scores were measured and compared using non-parametric statistical methods in relation to gender, region and type of household. Children with T1D reported lower quality of life comparing to matching controls with lower scores in almost all domains. Differences in the same domains among patients and their classmates were also observed in the different gender subgroups, environment type subgroups and in the central region. Results of the study provide insights to prioritizing actions for children with diabetes care as well as for public healthcare planning.

Trends in nationwide incidence of pediatric type 1 diabetes in Montenegro during the last 30 years.

Significant and unexplained variations in type 1 diabetes (T1D) incidence through the years were observed all around the world. The update on this disorder's incidence is crucial for adequate healthcare resource planning and monitoring of the disease. The aim of this study was to give an update on the current incidence of pediatric T1D in Montenegro and to analyze incidence changes over time and how the exposure to different factors might have affected it. This retrospective cohort study included a total of 582 patients younger than 15 years who were newly diagnosed with T1D during the past 30 years. The average age at diagnosis was 8.4 ± 3.91 years. The mean annual incidence of T1D in the Montenegro population during the whole study period of 30 years was 15.2/100,000 person-years. Slightly higher incidence rates were observed in male compared to female individuals, and the incidence increased with age, with the highest incidence in the 10-14 age group. If the model is observed as one without jointpoints, the annual percentage change (APC) for the total population is 3.1 (1.8-4.4); for male individuals, 3.8 (2.1-5.5); and for female individuals, 2.1 (0.6-3.5). In 2020, the first year of the coronavirus disease of 2019 (COVID-19) pandemic, in comparison to 2019, the incidence rate increased from 19.7/100,000 to 21.5/100,000, with the highest increase in the age group of 5-9 years. This is the first nationwide report on a 30-year period of T1D incidence trend in Montenegro. It suggests that T1D incidence among Montenegrin children is rising again and that there is a short-term influence of COVID-19 on new-onset T1D.

The landscape of Mucopolysaccharidosis in Southern and Eastern European countries: a survey from 19 specialistic centers.

BACKGROUND: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by defects in genes coding for different lysosomal enzymes which degrade glycosaminoglycans. Impaired lysosomal degradation causes cell dysfunction leading to progressive multiorgan involvement, disabling consequences and poor life expectancy. Enzyme replacement therapy (ERT) is now available for most MPS types, offering beneficial effects on disease progression and improving quality of life of patients. The landscape of MPS in Europe is not completely described and studies on availability of treatment show that ERT is not adequately implemented, particularly in Southern and Eastern Europe. In this study we performed a survey analysis in main specialist centers in Southern and Eastern European countries, to outline the picture of disease management in the region and understand ERT implementation. Since the considerable number of MPS IVA patients in the region, particularly adults, the study mainly focused on MPS IVA management and treatment. RESULTS: 19 experts from 14 Southern and Eastern European countries in total responded to the survey. Results outlined a picture of MPS management in the region, with a high number of MPS patients managed in the centers and a high level of care. MPS II was the most prevalent followed by MPS IVA, with a particular high number of adult patients. The study particularly focused on management and treatment of MPS IVA patients. Adherence to current European Guidelines for follow-up of MPS IVA patients is generally adequate, although some important assessments are reported as difficult due to the lack of MPS skilled specialists. Availability of ERT in Southern and Eastern European countries is generally in line with other European regions, even though regulatory, organizational and reimbursement constrains are demanding. CONCLUSIONS: The landscape of MPS in Southern and Eastern European countries is generally comparable to that of other European regions, regarding epidemiology, treatment accessibility and follow up difficulties. However, issues limiting ERT availability and reimbursement should be simplified, to start treatment as early as possible and make it available for more patients. Besides, educational programs dedicated to specialists should be implemented, particularly for pediatricians, clinical geneticists, surgeons, anesthesiologists and neurologists.

Current Status of Newborn Screening in Southeastern Europe.

Significant part of Southeastern Europe (with a population of 76 million) has newborn screening (NBS) programs non-harmonized with developed European countries. Initial survey was conducted in 2013/2014 among 11 countries from the region (Albania, Bulgaria, Bosnia and Herzegovina (BIH), Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, and Slovenia) to assess the main characteristics of their NBS programs and their future plans. Their cumulative population at that time was ~52,5 million. At that time, none of the countries had an expanded NBS program, while phenylketonuria screening was not introduced in four and congenital hypothyroidism in three of 11 countries. We repeated the survey in 2020 inviting the same 11 countries, adding Cyprus, Greece, Hungary, and Malta (due to their geographical position in the wider region). The aims were to assess the current state, to evaluate the change in the period, and to identify the main obstacles impacting the implementation of expanded NBS and/or reaching a wider population. Responses were collected from 12 countries (BIH-Federation of BIH, BIH-Republic of Srpska, Bulgaria, Croatia, Greece, Hungary, Kosovo, North Macedonia, Malta, Montenegro, Romania, Serbia, Slovenia) with a population of 68.5 million. The results of the survey showed that the regional situation regarding NBS only modestly improved in this period. All of the surveyed countries except Kosovo screened for at least congenital hypothyroidism, while phenylketonuria was not screened in four of 12 countries. Croatia and Slovenia implemented an expanded NBS program using tandem mass spectrometry from the time of last survey. In conclusion, the current status of NBS programs in Southeastern Europe is very variable and is still underdeveloped (or even non-existent) in some of the countries. We suggest establishing an international task-force to assist with implementation and harmonization of basic NBS services where needed.

Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010.

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders ("conditions") then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40-50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together.

Standardized Map of Iodine Status in Europe.

Background: Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods: We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results: In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from -36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 µg/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 µg/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC <150 µg/L. Conclusions: We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.

Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25 year period 1989-2013: a multicentre prospective registration study.

AIMS/HYPOTHESIS: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years. METHODS: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends. RESULTS: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012. CONCLUSIONS/INTERPRETATION: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.

RECENT INCIDENCE OF TYPE 1 DIABETES MELLITUS IN MONTENEGRO: A SHIFT TOWARD YOUNGER AGE AT DISEASE ONSET.

In the last several decades, a great number of studies have pointed to a dramatic increase of type 1 diabetes mellitus (T1DM) incidence in the whole world, especially in younger age groups. Therefore, the aim of the study was to assess changes in the age distribution at onset of T1DM in Montenegro children aged < 15 years during a 15-year period (1997-2011) and analyze the seasonal pattern. Primary case ascertainment was from diabetes register, secondary and tertiary independent data sources were hospital case records and register of children receiving free test stripes in pharmacy. Standardized incidence rates were calculated using the Poisson regression. Case ascertainment was 100% complete using the capture-recapture method. The mean age-standardized incidence was 18.6/100,000 (95% CI: 13.0-24.1) from 2007 to 2011 compared with 13.4/100,000 95% CI, 11.5-15.5) from 1997 to 2006. The incidence of T1DM increased predominantly in younger age groups. Relative increase of incidence per 5-year period was largest in boys aged 0-4 and 5-9 years: 64.7% (95% CI: 20.6-10.7; p = 0.004) and 52.8% (95% CI: 16.9-88.8; p = 0.004), respectively. Seasonality in monthly case counts of T1DM was apparent. The greatest number of cases were diagnosed during autumn and winter months. In conclusion, the onset of T1DM was found to occur at an ever younger age in Montenegro children. Our results indicated a seasonal pattern of the disease onset.

Health-related quality of life in children and adolescents with type 1 diabetes mellitus from Montenegro: relationship to metabolic control.

BACKGROUND: The aim of this study was to evaluate health-related quality of life (HRQOL) in children and adolescents with type 1 diabetes (TIDM) in Montenegro compared with healthy controls and to estimate the effect of metabolic control on perceptions of HRQOL. METHODS: This study involved children and adolescents with T1DM, age- and gender-matched healthy children and their parents. Children and adolescents with T1DM and their parents completed Peds QL 4.0 Generic Core Scales (GCS) and PedsQL 3.0 Diabetes Module. Healthy children and their parents completed self- and proxy-report of Peds QL 4.0 GCS. RESULTS: Our study (self- and proxy-report) showed that children and adolescents with T1DM had lower HRQOL on domain "Psychosocial health" and "School functioning" compared with healthy population (p=0.008; p≤0.001). Lower glycosylated hemoglobin (HbAlc) values were associated with fewer worries, and better health perception by diabetic children and their parents. We did not find notable differences between boys and girls on health perception. Different age groups reported similar QOL. Parents reported that the illness has a greater impact on children's lives than the children reported themselves. CONCLUSIONS: Compared with the healthy children, the HRQOL was lower among children and adolescents with T1DM. Lower HbA1c was associated with better quality of life.

Rising incidence of childhood type 1 diabetes in Montenegro.

Introduction: The incidence rate of childhood type1 diabetes continues to rise across Europe by an average of approximately 3­4% per annum. Objective: The aim of this study was to examine incidence and trends of type 1 diabetes in children aged 0­14 years in Montenegro from 1997 to 2011. Methods: This was a prospective study. Primary case ascertainment was from a diabetes register, and a secondary independent data source was from hospital notifications. Case ascertainment was 100% complete using the capture-recapture method. Standardized incidence rates were calculated and trends estimated using the Poisson regression. Results: A total of 298 children (157 boys and 141 girls) were diagnosed with type 1 diabetes before 15 years of age during 1997­2011. The mean age-standardized incidence was 15.0/100,000 persons (95% CI: 12.3­17.6) during this period, increasing from 11.7/100,000 in 1997 to 18.8/100,000 in 2011. The agespecific rates per 100,000 persons per year were 10.7, 17.2, and 18.2 at ages 0­4 years, 5­9 years, and 10­14 years, respectively. A significant linear trend in incidence (p = 0.002) has been observed over time, with an average annual increase of 4.2%. The increase in incidence was present in both genders, with the largest relative increase in the 0­4 years age group for boys (11.0%; p = 0.006). Conclusion: The incidence of type 1 diabetes in Montenegro children continues to increase. We need further monitoring and additional research in order to explain the cause.

Phenylketonuria screening and management in southeastern Europe - survey results from 11 countries.

BACKGROUND: We aimed to assess the current state of PKU screening and management in the region of southeastern Europe. METHODS: A survey was performed involving all identified professionals responsible for the PKU management in the 11 countries from South-Eastern region of Europe (Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, Slovenia). The questionnaire was designed to assess the characteristics regarding PKU management in three main areas: nation-wide characteristics, PKU screening, and characteristics of the PKU management in the responding centre. It consisted of 56 questions. The distribution and collection of the questionnaires (via e-mail) was taking place from December 2013 to March 2014. RESULTS: Responses from participants from 11 countries were included; the countries cumulative population is approx. 52.5 mio. PKU screening was not yet introduced in 4 of 11 countries. Reported PKU incidences ranged from 1/7325 to 1/39338 (and were not known for 5 countries). National PKU guidelines existed in 5 of 11 countries and 7 of 11 countries had PKU registry (registries included 40 to 194 patients). The number of PKU centers in each country varied from 1 to 6. Routine genetic diagnostics was reported in 4 of 11 countries. Most commonly used laboratory method to assess phenylalanine levels was fluorometric. Tetrahydrobiopterine was used in only 2 of 11 countries. Most frequently, pediatricians were caring for the patients. Dietitian was a member of PKU team in only 4 of 11 countries, while regular psychological assessments were performed in 6 of 11 countries. Patient's PKU society existed in 7 of 11 countries. CONCLUSIONS: The region of southeastern Europe was facing certain important challenges of PKU screening and management. Neonatal PKU screening should be introduced throughout the region. Furthermore, PKU management was falling behind internationally established standards-of-care in many aspects.

Prevalence of and contributing factors for overweight and obesity among Montenegrin schoolchildren.

BACKGROUND: Newly emerging Western style economic systems provide new opportunities to study the prevalence and predictors of childhood obesity. We also provide for the first time a national study of childhood obesity using all three international anthropometric criteria. METHODS: The sample included 4097 Montenegrin children, 2076 boys (50.7%) and 2021 girls. Anthropometric measurements were performed in school. The questionnaire for parents included questions on 24 potential contributing factors for childhood obesity. Nutritional status was assessed according to World Health Organization, US Center for Disease Prevention and Control and International Obesity Task Force (IOTF) criteria. RESULTS: Overall percentage of Montenegrin children who are overweight or obese (IOTF) is 22.9% of which 5.3% are obese (7.0% boys vs. 3.5% girls). We found 10 factors to be independently associated with child obesity. Positive relations [odds ratio (95% confidence interval)] were found with maternal obesity [2.05 (1.68-2.51)], paternal obesity [1.67 (1.32-2.10)], paternal employment [1.40 (1.12-1.74)], maternal smoking [1.32 (1.08-1.61)], obesity at birth [1.33 (1.04-1.70)] and computer game playing [per hour--1.11 (1.00-1.24)]. Negative relations were found with female gender [0.64 (0.53-0.78)], the number of siblings [0.88 (0.78-0.98)], birth order [0.73 (0.64-0.83)] and age [0.92 (0.88-0.98)]. CONCLUSION: One out of four Montenegrin children is overweight, with two times more frequent obesity among boys compared with girls. Some previously salient predictors did not appear salient in this sample. To enable worldwide comparability, we propose the use of all three childhood obesity criteria in national studies.

Newborn screening in southeastern Europe.

The aim of our study was to assess the current state of newborn screening (NBS) in the region of southeastern Europe, as an example of a developing region, focusing also on future plans. Responses were obtained from 11 countries. Phenylketonuria screening was not introduced in four of 11 countries, while congenital hypothyroidism screening was not introduced in three of them; extended NBS programs were non-existent. The primary challenges were identified. Implementation of NBS to developing countries worldwide should be considered as a priority.

Blood pressure among rural Montenegrin children in relation to poverty and gender.

BACKGROUND: Health inequalities may begin during childhood. The aim of this study was to investigate the main effect of poverty and its interactive effect with gender on children's blood pressure. METHODS: The study was performed in two elementary schools from a rural region near Podgorica, the capital of Montenegro. A questionnaire including questions on family monthly income, children's physical activity and the consumption of junk food was self-administered by parents of 434 children (223 boys and 211 girls) aged 6-13 years. Children's poverty level was assessed using the recommendations from the National Study on Poverty in Montenegro. Children's body weight and height were measured and body mass index-for-gender-and-age percentile was calculated. An oscillometric monitor was used for measurement of children's resting blood pressure in school. RESULTS: A two-factorial analysis of variance with body mass index percentile, physical activity and junk food as covariates showed an interaction of gender and poverty on children's blood pressure, pointing to synergy between poverty and female gender, with statistical significance for raised diastolic pressure (F = 5.462; P = 0.021). Neither physical activity nor the consumption of junk food explained the interactive effect of poverty and gender on blood pressure. CONCLUSION: We show that poverty is linked to elevated blood pressure for girls but not boys, and this effect is statistically significant for diastolic pressure. The results are discussed in the light of gender differences in stress and coping that are endemic to poverty.

Forensic aspects of water intoxication: four case reports and review of relevant literature.

Water intoxication (WI) is a rare condition that originates from over-consumption of water, with a potentially fatal outcome. Increased water intake (polydipsia) is followed by urination of high amount of diluted urine (polyuria) which are the main initial symptoms of WI. We present four case reports of WI. Two of them are unusual pediatric clinical cases using medical documentation and police case files, one of which is related to child abuse, and the other to a psychiatric disorder. The other two cases are fatal adult cases submitted to autopsy from a psychiatric hospital. Also, we present a diagnostic algorithm for polydipsia and polyuria before death. WI is usually seen in patients with psychiatric disorders, victims of child abuse or torture, drug abusers or it can be iatrogenically induced.

[Diabetic ketoacidosis in children with newly detected type 1 diabetes in Montenegro from 1999 to 2008].

INTRODUCTION: The aim of the study was to analyze the prevalence of diabetic ketoacidosis during the period of 10 years (1999-2008) among children diagnosed with type 1 diabetes in Montenegro. MATERIAL AND METHODS: A retrospective population-based incidence study was performed. The study participants were selected from two independent sources: the diabetes register and hospital records. The following parameters were measured before the first insulin injection: plasma glucose, blood gas analysis, electrolytes, creatinine, insulin, c-peptide, and HbA1c. Diabetic ketoacidosis was defined as pH <7.3 and severe diabetic ketoacidosis as pH <7.1. The obtained data were analysed using SPSS for Windows (version 17). RESULTS: During the study period, 208 children <15 years of age (107 boys and 101 girls) were found to have newly diagnosed type 1 diabetes. The age- and sex-standardized incidence rate was 15.8/100,000 children/yr. Of these, 51 (24.5%) presented with diabetic ketoacidosis at the time of diagnosis and 8 (3.8%) had a severe form. and no one died. In children <5 years the prevalence was 30.4%. We found no statistically important correlation between diabetic ketoacidosis incidence, pH value and the age of children (p>0.05). There was also no significant difference in diabetic ketoacidosis incidence between the boys and girls (p>0.05). CONCLUSION: The frequency of diabetic ketoacidosis in children with newly diagnosed type 1 diabetes in Montenegro is still high with a trend to decrease in the last ten years. In particular, children under 5 years of age are at a high risk of developing diabetic ketoacidosis at the onset.

Effect of growth hormone replacement therapy in a boy with Dent's disease: a case report.

INTRODUCTION: Dent's disease is an X-linked recessive proximal tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis and progressive renal failure. To the best of our knowledge, this is only the third report on the use of growth hormone therapy in a child with poor growth associated with Dent's disease. CASE PRESENTATION: We report on a 7-year-old Montenegrin boy with proteinuria, hypercalciuria, nephrocalcinosis, rickets and short stature with unimpaired growth hormone secretion. A molecular genetic analysis showed S244L substitution on the CLCN5 gene. After two years of conventional treatment with hydrochlorothiazide, laboratory tests revealed more prominent proteinuria, mild hypophosphatemia, increased values of alkaline phosphatase and features of rickets. Phosphate salts, calcitriol, potassium citrate and growth hormone were included in the therapy. After three years of therapy, his adjusted parental stature was 1.53 standard deviations higher than at the initiation of growth hormone therapy. His global kidney functions and levels of proteinuria and calciuria remained relatively stable. In spite of the growth hormone therapy, his tubular reabsorption of phosphate deteriorated. CONCLUSION: Treatment with recombinant human growth hormone may have a positive effect on final height in poorly growing children with Dent's disease and hypophosphatemic rickets. However, it is not possible to reach definite conclusions due to the small sample within the literature and the brief duration of the therapy.

Increasing incidence of childhood type 1 diabetes in Montenegro from 1997 to 2006.

OBJECTIVE: To determine and analyze the incidence of type 1 diabetes mellitus (T1DM) in 0- to 14-yr-old children in Montenegro from 1997 to 2006. RESEARCH DESIGN AND METHODS: This was a prospective study. Primary case ascertainment came from a diabetes register and secondary independent data source was from prescription data. Age and sex-standardized incidence rates were calculated using direct method, assuming an equal distribution in each age/sex group. The 95% confidence interval (CI) were estimated assuming the Poisson distribution. The independent effects of calendar year, two 5-yr time periods, sex and age groups were estimated with Poisson regression modeling. RESULTS: During the 10-yr period, 184 new cases of type 1 diabetes were identified. Case ascertainment was 100% complete using the capture-recapture method. The mean annual standardized incidence rate over the 10-yr period was 13.4/100 000/yr (95% CI: 11.5-15.5). It increased on average by 4.6% per year (95% CI: -0.4 to -9.6%, p = 0.07). The time-period specific incidence rate from year 1997 to 2001 was significantly lower (10.8; 8.5-13.5) compared with the second period from 2002 to 2006 (16.3; 13.3-19.7), (p < 0.0001). The age-specific incidence for the 0-4-yr age group was significantly lower (8.9; 6.3-12.3) than in 5- to 9-yr age group (14.1; 10.8-18.1); and in the 10-14 yr group (17.2; 13.7-21.3) per 100,000 children. CONCLUSIONS: The incidence rate in last 5 yr places Montenegro in the group of countries with moderate risk for development of type 1 diabetes in children. The average annual increase in incidence is 4.6%.

[Dent's disease].

INTRODUCTION: Dent disease is X-linked recessive proximal tubulopathy, due to mutations in the CLCN5 gene. It is characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis and progressive renal failure. CASE OUTLINE: A seven-year-old boy was referred after endocrinological examination where abdominal ultrasound showed nephrocalcinosis. There were anamnestic data neither of oedema, macrohaematuria, nor polyuria or hypertension. There were also no data of chronic renal failure in the family. We determined: proteinuria (1.8 g/day), elevated urinary excretion of Beta 2 microglobulin, microscopic haematuria, hypercalciuria (8-10 mg/kg/day), nephrocalcinosis, decreased tubular reabsorption phosphate (65%). Values of growth hormone, parathormone on thyroid hormone were normal. Except hypercalciuria, which was registered in the patient's mother, all other analyses performed in family members were between reference values. Diagnosis was finalized by mutation analysis, which showed S244L substitution on CNCL5. Mutation carrier was mother with normal phenotype. CONCLUSION: Dent disease is rare X-linked nephrocalcinosis. Definitive diagnosis of this proximal tubulopathy which leads to progressive renal damage is not possible without evidence of gene mutation in renal chlorine channel.