First report on the nationwide incidence of type 1 diabetes and ketoacidosis at onset in children in Serbia: a multicenter study.

Data regarding incidence of type 1 diabetes (T1DM), as well as data on frequency and severity of diabetic ketoacidosis (DKA) at the time of T1DM diagnosis is of paramount importance for national and regional healthcare planning. The aim of present multicenter study was to provide the first report regarding nationwide annual incidence rates for T1DM in youth in Serbia, as well as prevalence of DKA at the time of diagnosis. Data on all pediatric patients with newly diagnosed T1DM was retrospectively collected from all 15 regional centers for pediatric diabetes in Serbia during the period 2007-2017. During the study period, average-standardized incidence of T1DM in youth < 19 years was 11.82/100,000, and 14.28/100,000 in 0-14 years age group, with an average yearly increase in incidence of 5.9%. High prevalence of DKA (35.1%) at the time of diagnosis was observed, with highest frequency in children aged < 5 years (47.2%). CONCLUSION: This is the first study reporting the nationwide incidence of T1DM and alarmingly high prevalence of DKA at diagnosis in youth in Serbia. The focus of public health preventive measures should be directed towards the preschoolers, considering the highest frequency and severity of DKA observed in this age group. What is Known: • Knowing regional T1DM incidence is of paramount importance for resource allocation and healthcare services provision. • DKA is the leading cause of acute mortality in youth with T1DM, and public health preventive educational measures could improve early diagnosis and reduce the frequency and severity of DKA at presentation. What is New: • Incidence of pediatric T1DM in Serbia is on the rise, with an average yearly increase of 5.9%. • Worryingly high prevalence of DKA (35.1%) at the time of T1DM diagnosis was observed, with the highest frequency of DKA in children aged < 5 years (47.2%).

Ketoacidosis at presentation of type 1 diabetes mellitus in children: a retrospective 20-year experience from a tertiary care hospital in Serbia.

UNLABELLED: Diabetic ketoacidosis (DKA) has significant morbidity and mortality and is common at diagnosis in children. The aim of this study was to determine the frequency and clinical characteristics of DKA over a 20-year period among children diagnosed with type 1 diabetes mellitus (T1DM) at University children's hospital in Belgrade, Serbia. The study population comprised of 720 patients (366 boys) diagnosed with type 1 diabetes aged <18 years between January 1992 and December 2011. Of all patients diagnosed with T1DM, 237 (32.9 %) presented with DKA. The majority had either mild (69.6 %) or moderate (22.8 %) DKA. Sixty (55.0 %) of all children under 5 years had DKA compared to sixty-two (20.9 %) in the 5- to 10-year-old group and one hundred fifteen (36.6 %) in the 11- to 18-year-old patients (p<0.01), while 2.5 % of the entire DKA cohort were in real coma. During the later 10-year period, children less often had DKA at diagnosis compared with the earlier 10-year period (28.0 vs. 37.4 %) (p<0.01), but the frequency of severe DKA was higher in the age group <5 year and in the age group >11 year during 2002-2011, compared with the earlier 10-year period (12.9 vs. 3.4 %, p<0.01 and 17.1 vs. 3.8 %, p<0.01). CONCLUSION: The overall frequency of DKA in children with newly diagnosed type 1 diabetes decreased over a 20-year period at our hospital. However, children aged <5 years and adolescents are still at high risk for DKA at diagnosis.

First report on the nationwide prevalence of paediatric type 1 diabetes in Serbia and temporal trends of diabetes ketoacidosis at diagnosis-a multicentre study.

We aimed to collect data on all paediatric patients who were diagnosed with type 1 diabetes mellitus (T1DM) between the years 2000 and 2019 in Serbia and estimate for the first time its prevalence. Also, the trends of diabetes ketoacidosis (DKA) occurrence at the time of diagnosis are monitored. We collected and retrospectively analysed the data of patients <19 years with newly diagnosed T1DM. T1DM was diagnosed in 3134 patients (53.2% male). Total number of youth <19 years with T1DM was 1735 with prevalence of 135.25/100000 at the end of study period. T1DM was diagnosed most frequently between the ages of 5 and 11 years (42.1%). At the time of diagnosis, 35.7% presented in DKA. The incidence and severity of DKA were more significant at the youngest age (p<0.001). There were significant annual percentage increase (2.2%) in the number of new cases of DKA (p=0.007). Conclusion: This first report of nationwide prevalence of T1DM in youth shows that Serbia is among countries with high prevalence of T1DM in youth. System changes are needed in order to provide better quality of health care to these patients.

The importance of combined NGS and MLPA genetic tests for differential diagnosis of maturity onset diabetes of the young.

INTRODUCTION: Maturity onset diabetes of the young (MODY) is a rare form of monogenic diabetes. Being clinically and genetically heterogeneous, it is often misdiagnosed as type 1 or type 2 diabetes, leading to inappropriate therapy. MODY is caused by a single gene mutation. Thirteen genes, defining 13 subtypes, have been identified to cause MODY. A correct diagnosis is important for the right therapy, prognosis, and genetic counselling. MATERIAL AND METHODS: Twenty-nine unrelated paediatric patients clinically suspected of having MODY diabetes were analysed using TruSight One panel for next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) assay. RESULTS: In this study we identified variants in MODY genes in 22 out of 29 patients (75.9%). Using two genetic tests, NGS and MLPA, we detected both single nucleotide variants and large deletions in patients. Most of the patients harboured a variant in the GCK gene (11/22), followed by HNF1B (5/22). The rest of the variants were found in the NEUROD1 and HNF1A genes. We identified one novel variant in the GCK gene: c.596T>C, p.Val199Ala. The applied genetic tests excluded the suspected diagnosis of MODY in two patients and revealed variants in other genes possibly associated with the patient's clinical phenotype. CONCLUSIONS: In our group of MODY patients most variants were found in the GCK gene, followed by variants in HNF1B, NEUROD1, and HNF1A genes. The combined NGS and MLPA-based genetic tests presented a comprehensive approach for analysing patients with suspected MODY diabetes and provided a successful differential diagnosis of MODY subtypes.

Stressful life events and psychological dysfunctions before the onset of type 1 diabetes mellitus.

AIM: To test the hypothesis that stressful life events and psychological dysfunction increase the risk for development of type 1 diabetes mellitus (DM1). METHOD: A case-control study comprising 105 children with DM1 and 210 controls matched by age +/- 1 year), sex and place of residence. Conditional univariate and multivariate logistic regressions were used to analyze the data. RESULTS: After adjustment for possible confounders, the following factors were positively related to DM1: parents' job-related issues changed or lost job (odds ratio [OR] 11.5, 95% confidence interval [CI] 1.6-81.8); other severe life events--severe accident, hospitalization or death of close friend, quarrels between parents, war in republics of former Yugoslavia, near-drowning in a pool, falling down, unhurt participant of an accident (OR 68.5, 95% CI 13.5-349.0); other minor life events--conflicts with parents/teacher/neighbors, lost in town, physical attack, failure in competition, penalty, examination, death of pet, presence at lightning strike, thrown out of dwelling (OR 32.7, 95% CI 6.3-169.6); and learning problems (OR 17.5, 95% CI 4.3-71.6). CONCLUSION: These results support the hypothesis that stressful life events and psychological dysfunctions are associated with DM1.

Problems in diabetes managment in school setting in children and adolescents with type 1 diabetes in Serbia.

RESULTS: The obtained results show that not all children test blood glucose levels at school (50% of children in the 6-10-year-old age group and 67.3% in the age group over 11 years) and that not all children receive insulin at school (81.1% vs. 18.9%, and 57.7% vs. 42.3%, respectively). The frequency of severe hypoglycemia was 2.7% in children and 3.3% in adolescents. A high proportion of teachers did not have diabetes training. CONCLUSION: This brief report about problems in children and adolescents with type 1 diabetes at school in Serbia indicates what happens in the school setting and suggests how to improve control of this disease and facilitate the complete integration of children with diabetes at school. BACKGROUND/AIM: Children with type 1 diabetes typically spend one-third of the day in school and they should achieve the same level of diabetes management there as they do outside the school environment. The aim of this study was to identify problems in diabetes management in children with type 1 diabetes at school according to the perceptions reported by children and parents. METHODS: This cross-sectional survey was carried out at nine public hospitals in Serbia with a cohort of 6-18-year old children/adolescents. The parents were personally informed about the objectives of the survey and the necessity to involve their children. The self-reporting questionnaire included demographic information as well as some questions that helped to evaluate the general situation of children with type 1 diabetes at school.

Early infant diet and risk of type 1 diabetes mellitus in Belgrade children.

OBJECTIVES: This study investigated whether an infant diet is associated with the development of type 1 diabetes. METHODS: A case-control study was conducted in Belgrade from 1994 to 1997. A total of 105 patients with recent onset diabetes (< or = 16 y old) were compared with 210 controls chosen among children with skin disease (first control group). Cases and controls were individually matched by age (+/-1 y), sex, and place of residence. Eighty-six children with diabetes were also compared with their siblings (second control group). RESULTS: According to univariate logistic regression analysis, when cases were compared with the first control group, the risk of type 1 diabetes was greater for children who were breast fed less than 4 mo (odds ratio = 2.09, 95% confidence interval = 1.30 to 3.36) and who received cow's milk at younger than 5 mo (odds ratio = 3.39, 95% confidence interval = 2.04 to 5.66). According to univariate analysis, when cases were compared with their relatives, only early introduction of supplementary milk was associated with a higher risk for diabetes (odds ratio = 5.75, 95% confidence interval = 2.91 to 11.36). After adjusting for different confounding variables, infant diet was not independently associated with diabetes. CONCLUSIONS: The results obtained do not support the hypothesis that infant diet is related to the occurrence of type 1 diabetes.

The Diagnosis of Prediabetes in Adolescents.

BACKGROUND: Prediabetes is characterized by isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT. This study aimed to establish the prevalence of prediabetes and examine possible contributory factors in a cohort of obese adolescents. METHODS: In this prospective study, we recruited 85 obese patients from the Obesity Clinic at the University Children's Hospital and 17 normal weight controls. All patients were of Caucasian origin, 60 males/42 females, aged 7.4-18.3 years, with at least Tanner 2 stage of puberty. RESULTS: Depending on criteria we used, insulin resistance was confirmed in 62-100% of obese patients, predominantly in the group with BMI SDS > 3. oGTT revealed isolated impaired fasting glucose (IFG) in 13.9%, impaired glucose tolerance (IGT) in 20.8% and combined IFG and IGT only in 2.8% of the obese patients. Patients in the prediabetes group were older (14±2.4 vs 12.8±2.5 p=0.04) and had higher glucose levels (p<0.001) during the whole oGTT compared to normal glucose tolerance (NGT) group. There was no difference between groups in respect to family history, BMI, lipids and fasting insulin. Insulinogenic index, WBISI and HOMA%B were significantly lower in the prediabetes group compared to the NGT group (p=0.07, 0.01 and 0.04 respectively). HbA1c level was measured in 58% of patients and was significantly higher in the prediabetes group (5.4±0.3 vs 5.7±0.4, p=0.002). CONCLUSION: Prediabetes occurrence was fairly high in our obese adolescents. Further studies should establish what would be the most appropriate screening test to diagnose these patients at risk for type 2 diabetes and initiate treatment without delay.

Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634).

INTRODUCTION: The multiple endocrine neoplasia type 2A (MEN 2A) syndrome, comprising medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism (PHPT) is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection) proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years) would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. CASE OUTLINE: This is a case report of 3-year-old boy from the MEN 2A family (the boy's father and grandmother and paternal aunt) in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is < 2 pg/ml (normal < 13 pg/ml), has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. CONCLUSION: Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years.

The effect of metabolic and hormonal parameters on microalbuminuria in adolescents with type 1 diabetes mellitus.

INTRODUCTION: The prevalence of microalbuminuria (MA), the most important early marker of incipient nephropathy in patients with type 1 diabetes mellitus (T1DM), increases during puberty, the period of exaggerated physiological insulin resistance. OBJECTIVE: To assess the prevalence of MA and the relationship between MA and metabolic risk factors and pubertal hormones in adolescents with T1DM. METHODS: In a cross-section study involving a group of 100 adolescents of both sexes of mean age 14.90+/-2.18 years and with mean duration ofT1DM 5.99+/-73.64 years, we assessed the presence of MA. In all patients, we determined albumin-to-creatinine ratio (ACR) in two or three morning first-void urine samples in the period up to 6 months. Persistent MA was confirmed in the patients with the finding of ACR rating 2.5-25 mg/mmol in males and 3.5-25 mg/mmol in females in two out of three first morning urine samples. RESULTS: MA developed in 16 (16.0%) patients. Predictors of MA determined by using multiple logistic regression were high HbA1c (OR 4.6; 95% CI 2.1-10.0), higher night-time SBP (OR 1.9; 95% CI 0.8-1.3) and higher insulin dose (OR 62.6; 95% CI 2.3-1678.5). Markers of insulin resistance such as higher body mass index (BMI) which was statistically significantly related to MA (p= 0.241, p<0.05) and higher dehydroepiandrosterone sulfate (DHEA-S) which was significantly higher in patients with MA (7.82 micromol/L vs. 5.02 micromol/L, p<0.01), were also identified as predictors but did not remain significant by multivariate analysis, possibly because of a small sample of subjects with persistent MA. CONCLUSION: In addition to poor glycemic control and higher night-time systolic blood pressure, markers of insulin resistance (higher insulin dose, higher BMI and higher DHEA-S) contribute to the increased risk of MA.

Premature ovarian failure.

Premature ovarian failure (POF) is the occurrence of hypergonadotropic hypoestrogenic amenorrhea in women under the age of forty years. It is idiopathic in 74-90% patients. Known cases can be divided into primary and secondary POF. In primary POF genetic aberrations can involve the X chromosome (monosomy, trisomy, translocations, deletions) or autosomes. Genetic mechanisms include reduced gene dosage and non-specific chromosome effects impairing meiosis, decreasing the pool of primordial follicles and increasing atresia due to apoptosis or failure of follicle maturation. Autoimmune ovarian damage is caused by alteration of T-cell subsets and T-cell mediated injury, increase of autoantibody producing B-cells, a low number of effector/cytotoxic lymphocyte, which decreases the number and activity of natural killer cells. Bilateral oophorectomy, chemotherapy, radiotherapy and infections cause the secondary POF. Symptoms of POF include irritability, nervousness, loss of libido, depression, lack of concentration, hot flushes, weight gaining, dry skin, vaginal dryness, frequent infections etc.The diagnosis is confirmed by the level of FSH of over 40 IU/L and estradiol below 50 pmol/L in women aged below 40 years. Biochemical and other hormonal analysis (free thyroxin, TSH, prolactin, testosterone), karyotype (<30 years of age), ultrasound of the breasts and pelvis are advisable. Optimal therapy is combined estrogen progestagen therapy given in a sequential rhythm, after excluding absolute contraindications. Testosterone can be added to adnexectomized women and those with a low libido. Sequential estrogen progestagen replacement therapy is the first line therapy for ovulation induction in those looking for pregnancy and after that oocyte donation will be advised. Appropriate estro-progestagen therapy improves the quality of life and prevents complications such as cardiovascular diseases, osteoporosis, stroke etc.

[Elements of metabolic control in children with type 1 diabetes before and after introduction to insulin analogues].

INTRODUCTION: Diabetes mellitus type 1 (T1DM) in children is characterized by unstable course. A significant number of studies shows that introduction to insulin analogues treatment aims towards better control of the disease. OBJECTIVE: The assessment of metabolic control in children with T1DM that were introduced to insulin analogue treatment after many years of treatment with classic (human) insulin. METHODS: The study included 59 patients 2-19 years old (12.9 +/- 3.8) with T1DM, transferred from treatment with human insulin to insulin analogues treatment. Data were obtained directly from patients and their parents, as well as from medical records. RESULTS: The introduction to insulin analogues treatment, leads to a decrease in the value of glycolized haemoglobin (HbA1c) after 6 months (9.27 +/- 1.68% vs 8.63 +/- 1:26%, p=0.06). Average daily dose of insulin expressed per IU/kg of classic and insulin analogue (1.04 +/- 0.38 vs 1.03 +/- 0.30; p>0.05), remained almost the same. In 39 examinees (66.1%), 6 months before the introduction to insulin analogue treatment, severe hypoglicemia was registered and 6 months after the introduction to insulin analogue treatment it appeared in only two examinees (3.4%) (p<0.001). Ketoacidosis, 6 months before introduction to insulin analogues treatment, appeared in 16 examinees (27.1%), while 6 months after it was not registered (p<0.001). CONCLUSION: The use of insulin analogue treatment in childhood provides adequate metabolic control and substantially reduces the risk of acute complications (severe hypoglicemia, ketoacidosis).

Successful sulfonylurea treatment of a neonate with neonatal diabetes mellitus due to a new KCNJ11 mutation.

Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-sensitive potassium channel, often result in neonatal diabetes. We describe a female neonate who is a heterozygous for a new missense mutation, V252L, in the KCNJ11 gene and who has been successfully transitioned from insulin to sulfonylurea therapy.

Microalbuminuria in relation to metabolic control and blood pressure in adolescents with type 1 diabetes.

INTRODUCTION: The objective of this study was to assess the frequency of microalbuminuria and the relationship with other risk factors for the development of diabetic nephropathy. MATERIAL AND METHODS: Our cross-section study involved a group of 60 adolescence of both sexes, mean age 15.3 ±2.43 years with mean duration of diabetes 7.74 ±3.44 years. Albumin excretion rate was measured on 2-3 samples of the first morning urine in the period below 6 months and persistent microalbuminuria was defined if its increased in two out of three urine specimens. Ambulatory blood pressure was monitored (ABPM, SpaceLabs 90207). RESULTS: Microalbuminuria developed in 13.3% of adolescents with mostly completed sexual development, statistically significantly poorer metabolic control (9.79% vs. 8.7%) and higher BMI (23.59 kg/m(2) vs. 20.85 kg/m(2)) than in the patients with normoalbuminuria. The mean night-time systolic blood pressure (SBP) was statistically significantly higher in microalbuminuric patients than in normoalbuminurics. The nocturnal dip was reduced in 41.7% of our patients; 38.5% of nondippers were in normoalbuminuric and 62.5% in microalbuminuric patients. CONCLUSIONS: Diabetic adolescents require particular attention in order to minimize the factors such as high HbA(1c), elevated body mass index and night-time SBP in the development of incipient nephropathy.

A case of new mutation in maturity-onset diabetes of the young type 3 (MODY 3) responsive to a low dose of sulphonylurea.

We describe a girl aged 10.5 years with hyperglycemia, whose mother and maternal father had insulin treated diabetes since adolescence. Using genetic analysis in mother and child, we identified identical new mutation of the HNF-1alpha sequence. Treatment with small doses of sulphonylurea was initiated and that therapy gave good results.

[IPEX syndrome--case report].

INTRODUCTION: IPEX syndrome, namely, a hereditary (X-linked) immunodysregulation with autoimmune polyendocrinopathy and enteropathy, as the basic manifestations, presents a rare and exceptionally severe disease. It develops due to gene mutation responsible for the synthesis of a specific protein (FOXP3), which, by differentiation and activation of regular T-lymphocytic CD4+CD25+, has the key role in the induction and maintenance of the peripheral tolerance of one's own tissue. CASE OUTLINE: We present a male infant with classic clinical features of IPEX syndrome, which manifested by the end of the first month after birth, first with type 1 diabetes mellitus and chronic diarrhoea followed by dehydration and disordered development, and then with facial eczema and laboratory signs of thyroiditis without thyroid dysfunction (antithyreoglobulin antibodies 1:5500, antimicrosomal antibodies 1:40). In addition, plasma IgE level was high (517 IU/l), while antibodies to tissue transglutaminase were mildly increased (IgA 7.5 U/ml), and anti-smooth muscle and anti-DNA antibodies were absent. Based on the typical clinical features, as well as the laboratory findings, IPEX syndrome was diagnosed, which was further confirmed by proved IVS7+5G>A mutations in the FOXP3 gene. Therapy with insulin and Pronison, combined with parenteral and semielementary nutrition resulted in the patient's clinical improvement. At the age of 9 months, despite Pronison and hypoallergenic nutrition, the child had a relapse of severe and persistent diarrhoeal disorder followed by dehydration, weight loss and deterioration of general condition. Beside the complete parenteral nutrition, as well as other measures, azathioprine was introduced into the treatment, but without the desired effect. At the age of 12.5 months, due to bacteraemia and disseminated intravascular coagulation as complications, the patient ended lethally. CONCLUSION: IPEX syndrome should be kept in mind in all the cases of associated type 1 diabetes mellitus and chronic diarrhoea in male neonates or infants. Although treatment results have still been modest, it is quite certain they will be far better in the near future.

[Lingual thyroid].

Lingual thyroid is a rare congenital malformation that occurs more frequently in the female population. It occurs because of the error in transcriptional factors, the key for the normal differentiation of thyrocyte, so the thyroid gland tissue does not descend normally down the thyroglossal duct to the final position in the neck. Due to that, it can entirely or partially remain at the base of the tongue. This is the most frequent localization of the ectopic tissue while it can remain in the sublingual, suprahyoid and infrahyoid area as well. This disease can be diagnosed in the asymptomatic phase, as well as in the phase of compensatory and manifest hypothyroidism. In the ectopic thyroid gland, all diseases of the thyroid gland can occur as in the usual localization in the neck. The authors show a 6-year old patient, who had a routine medical examination for the inflamed throat, during which a vascular tumefaction was discovered at the base of the tongue. A cyst at the base of the tongue was suspected, but additional examination showed that it was an ectopic thyroid tissue marked as a lingual thyroid gland. Diagnosis of this disease starts with the laboratory analysis of the thyroid status. The next step involves scintigraphy of the thyroid gland with technetium-pertechnetate (99mTc) or radioactive iodine (123I). The therapy of the compensatory hypothyroidism is suppressive therapy with levothyroxine and in the manifest hypothyroidism it is hormone substitution therapy with levothyroxine. Although there are recommended age-related daily doses, they should not be accepted as final, but rather prescribed according to the individual thyroid status.

[Transient neonatal pseudohypoparathyroidism].

INTRODUCTION: Pseudohypoparathyroidism (PHP) is a heterogeneous group of diseases characterized by end organ unresponsiveness to parathormone (PTH), due to receptor or postreceptor defects. The characteristic biochemical disturbances include hypocalcaemia, hyperphosphataemia and high serum parathormone levels. CASE OUTLINE: We present a 17-day-old male baby who was brought to our hospital because of seizures. He was found to have hypocalcaemia, hyperphosphataemia and an elevated serum level of parathyroid hormone. The diagnosis of PHP was based on the elevated serum level of PTH during hypocalcaemia and persistence of normocalcaemia after administering alphacalcidiol with oral calcium. After 4 months of therapy, with tapering of the oral calcium doses, the treatment was discontinued. During the following six months without therapy, the infant did not have seizures and the serum levels of calcium and phosphorus were normal, so we established the final diagnosis of transient neonatal pseudohypoparathyroidism. CONCLUSION: At the time when the newborn was diagnosed to have PHP, there was no indication whether it was of a permanent or transient form. A considerably lower number of patients have a transitory form of PHP, which is then confirmed in the infant period by a gradual reduction and withdrawal of therapy, with sustaining serum calcium and PTH within normal limits.

[Camptomelic dysplasia--a case report].

Campomelic/camptomelic dysplasia is a very rare, severe osteochondrodysplasia characterised by severe skeletal and nonskeletal malformations and lethal outcome mainly in neonatal period. Characteristic abnormality by which the syndrome got its name is short, bowed long bones of lower extremities, most often of femur, manifested by short and bowed legs. Skin dimpling on tibial anterior side is another prominent characteristic of this syndrome. Severe cases are inherited by autosomal dominant trait, by mutation Sox9 gene on chromosome 17, with lethal outcome in the first days of life. Less severe forms of the disease are due to balanced translocation t (13;17) with life span up to the third decade of life. A majority of karyotypic males present as phenotypic females. We report a case of a female neonate, without consanguinity between parents, with characteristic signs of camptomelic dysplasia with short birth length of 46 cm, macrocephaly (head circumference 39 cm), dolichocephaly, hydrocephalus, short trunk and legs. Narrow rib cage, bowed lower extremities, short hand and foot phalanges, nail hypoplasia were noticed. Anterior fontanelle was enlarged, high forehead, face small and flat, hypertelorism, low nasal bridge, micrognathia, low set ears, cleft palate, were found. Characteristc skin dimpling on anterior side of tibia was present on both legs. Bone X-ray studies presented the following changes: anterior bowing of shortened femurs, hip dislocation, cervical vertebrae, scapulas, eleven pairs of slender ribs. Hip luxation. Karyotype was normal for a female, 46 XX. Respiratory insufficiency was present since birth, exacerbated, and led to lethal outcome in the second day of life, as described in the majority of these patients.

The Belgrade childhood diabetes study - comparison of children with type 1 diabetes with their siblings.

A case-control study was conducted in Belgrade (about 320,000 inhabitants 0-16 years old) during the period 1994-97, comprising 68 diabetic children (cases) and 68 controls chosen from the siblings of the cases. Analysis using multivariable logistic regression analysis indicated the following independent risk factors for Type 1 diabetes: higher birth order, infections during the 6 months preceding the onset of the disease and stressful events. Out of individual stressful and psychological factors, 'other' stressful events (severe accident or hospitalisation or death of a close friend, conflict with a teacher, death of a pet, failure in competition, quarrel between parents, punishment, physical attack, war in republics of former Yugoslavia and near drowning in the pool) and learning problems were independent risk factor for Type 1 diabetes. The results obtained in this study of siblings supports the hypothesis that environmental factors play a role in the development of Type 1 diabetes.