Browsing by Author "Jesic, Maja (24073164000)"

Background: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder with heterogeneous presentation, where acute encephalopathy is rarely described in literature. Therefore, initial neurologic symptoms could make the diagnosis and treatment challenging. Case presentation: A four-month-old male infant presented with acute encephalopathy, vomiting, bulging fontanel, decreased appetite and failure to thrive. He had extremely lipemic serum and anemia. Intracranial computed tomography (CT) revealed lipid collection which was suspected to be epidermoid cyst, and also lipid deposits with extra-axial and intravascular location. This was initially described as a ruptured intracranial epidermoid cyst with dissemination of lipid content, including intravascular dissemination. Together with clinical signs of raised intracranial pressure it was discussed whether the cyst should be surgically removed. Since the blood sample appearence was milky and the child was rather stable, surgery wasn’t performed and the treatment with exchange transfusion (ET) was started immediately. Only after ET it was possible to obtain laboratory results including lipid status (triglycerides were 106.8 mmol/l). At that point we suspected that the underlining cause is a genetic disease. Three cycles of plasmapheresis followed ET, after which symptoms resolved almost completely, despite remaining lipid deposits on brain CT scan and brain ultrasound, with some signs of regression. After these repeated imaging studies, it was concluded that the ‘cyst’ was actually the largest brain lipid collection. The definitive genetic diagnosis confirmed FCS. A short course of insulin, antioxidants and fibrates was initially given, but discontinued after the diagnosis confirmation due to lack of supporting data in the literature. Effective and the only maintenance treatment was the diet consisting of formula low in fat and high in medium-chain triglycerides. On the discharge the infant’s neurological status, except mild hypotonia, was normal, he was thriving well, had good appetite and no anemia. Conclusions: This is a rare case of FCS presenting with neurological symptoms that mimicked the clinical picture of ruptured intracranial epidermoid cyst, which was initially the differential diagnosis of this case. Initial interpretation of imaging studies didn’t delay treatment. With the right treatment, the symptoms of the disease could be reversible with satisfactory outcome. © The Author(s) 2024.

Objectives: This study aims to show the distribution of angiotensin-converting enzyme (ACE) rs1799752 (I>D) gene insertion/deletion (I/D) polymorphism and angiotensin II receptor type 1 (AGTR1) rs5186 (A>C) gene polymorphism in adolescents with hypertension (HT) and type 1 diabetes (T1D), as well as its association with hypertension and the diurnal variation of mean blood pressure (dipping phenomenon). Methods: A cross-sectional study was conducted involving 118 adolescents diagnosed with T1D who underwent clinical and laboratory investigations, genetic analyses, and 24 h ambulatory blood pressure monitoring. The genotype frequencies were compared between adolescents with HT and those with normal blood pressure. Additionally, the genotype frequencies were compared between dippers and non-dippers. Results: Patients with HT were more likely to be female and exhibited significantly poorer glycemic control and higher triglycerides, along with increased body mass index and daily insulin dosage. The prevalence of ACE rs1799752 genotypes in the hypertensive group was 20% II, 66.7% ID, and 13.3% DD, which did not significantly differ from the normal blood pressure group with 29.1% II, 53.4% ID, and 17.5% DD (p = 0.625). The prevalence of AGTR1 rs5186 genotypes in the hypertensive group was 53.3% AC, 40% AA, and 6.7% CC, which also did not significantly differ from the normal blood pressure group with 39.8% AC, 52.4% AA, and 7.8% CC (p = 0.608). A total of 46% of the patients exhibited non-dipping phenomena. The prevalence of non-dippers among the ACE genotypes was 13% DD, 33.3% II, and 53.7% ID (p = 0.369), while for the AGTR1 genotypes, it was 50% AA, 42.6% AC, and 7.4% CC (p = 0.976). Conclusions: Our results indicate that in our adolescents with T1D, clinical and metabolic factors such as higher body mass index, triglycerides, suboptimal glycemic control, and female gender are more indicative of the development of hypertension than ACE and AGTR1 gene polymorphisms. A potential reason for this finding could be the young age of the patients or the relatively small size of the study group. Future research involving larger sample sizes is needed to further investigate the genetic predisposition for the development of hypertension. © 2025 by the authors.

Objectives: This study aims to show the distribution of angiotensin-converting enzyme (ACE) rs1799752 (I>D) gene insertion/deletion (I/D) polymorphism and angiotensin II receptor type 1 (AGTR1) rs5186 (A>C) gene polymorphism in adolescents with hypertension (HT) and type 1 diabetes (T1D), as well as its association with hypertension and the diurnal variation of mean blood pressure (dipping phenomenon). Methods: A cross-sectional study was conducted involving 118 adolescents diagnosed with T1D who underwent clinical and laboratory investigations, genetic analyses, and 24 h ambulatory blood pressure monitoring. The genotype frequencies were compared between adolescents with HT and those with normal blood pressure. Additionally, the genotype frequencies were compared between dippers and non-dippers. Results: Patients with HT were more likely to be female and exhibited significantly poorer glycemic control and higher triglycerides, along with increased body mass index and daily insulin dosage. The prevalence of ACE rs1799752 genotypes in the hypertensive group was 20% II, 66.7% ID, and 13.3% DD, which did not significantly differ from the normal blood pressure group with 29.1% II, 53.4% ID, and 17.5% DD (p = 0.625). The prevalence of AGTR1 rs5186 genotypes in the hypertensive group was 53.3% AC, 40% AA, and 6.7% CC, which also did not significantly differ from the normal blood pressure group with 39.8% AC, 52.4% AA, and 7.8% CC (p = 0.608). A total of 46% of the patients exhibited non-dipping phenomena. The prevalence of non-dippers among the ACE genotypes was 13% DD, 33.3% II, and 53.7% ID (p = 0.369), while for the AGTR1 genotypes, it was 50% AA, 42.6% AC, and 7.4% CC (p = 0.976). Conclusions: Our results indicate that in our adolescents with T1D, clinical and metabolic factors such as higher body mass index, triglycerides, suboptimal glycemic control, and female gender are more indicative of the development of hypertension than ACE and AGTR1 gene polymorphisms. A potential reason for this finding could be the young age of the patients or the relatively small size of the study group. Future research involving larger sample sizes is needed to further investigate the genetic predisposition for the development of hypertension. © 2025 by the authors.

Diabetic ketoacidosis is an acute complication in children with type 1 diabetes mellitus. It is diagnosed if the sugar value is > 11 mmol/l, pH <7.3, HCO3-≤ 15 mmol/l, with ketonemia or ketonuria. Based on serum pH and bicarbonate values it could be mild, moderate, and severe. It is manifested by rapid breathing, abdominal pain, nausea, vomiting, altered state of consciousness. Early recognition of symptoms prevents the possibility of serious complications. Treatment includes fluid replacement, rehydration, insulin therapy, electrolyte replacement, glucose correction. This paper presents female patients, aged 2.5 to 15.3 years, with different symptoms. Clinical findings and laboratory test results indicated diabetic ketoacidosis. After starting urgent therapy, they were referred to intensive care units in tertiary centers, where it was concluded that the resulting condition was a newly-diagnosed type 1 diabetes mellitus. Such patients require early recognition of symptoms, urgent care, and treatment in intensive care units, in order to prevent possible complications. © 2021, Serbian Medical Society. All rights reserved.

Objective: To analyze metabolic parameters, body composition (BC), and bone mineral density (BMD) in childhood-onset GH deficiency (COGHD) patients during the transition period (TP). Design: Single-center, retrospective study was performed on 170 consecutive COGHD patients (age 19.2 ± 2.0 years, range 16–25) transferred after growth completion from two pediatric clinics to the adult endocrine unit. Two separate analyses were performed: (i) cross-sectional analysis of hormonal status, metabolic parameters, BC, and BMD at first evaluation after transfer from pediatrics to the adult department; (ii) longitudinal analysis of BC and BMD dynamics after 3 years of GH replacement therapy (rhGH) in TP. Results: COGHD was of a congenital cause (CONG) in 50.6% subjects, tumor-related (TUMC) in 23.5%, and idiopathic (IDOP) in 25.9%. TUMC patients had increased insulin and lipids levels (P < 0.01) and lower Z score at L-spine (P < 0.05) compared to CONG and IDOP groups. Patients treated with rhGH in childhood demonstrated lower fat mass and increased BMD compared to the rhGH-untreated group (P < 0.01). Three years of rhGH after growth completion resulted in a significant increase in lean body mass (12.1%) and BMD at L-spine (6.9%), parallel with a decrease in FM (5.2%). Conclusion: The effect of rhGH in childhood is invaluable for metabolic status, BC, and BMD in transition to adulthood. Tumor-related COGHD subjects are at higher risk for metabolic abnormalities, alteration of body composition, and decreased BMD, compared to those with COGHD of other causes. Continuation of rhGH in transition is important for improving BC and BMD in patients with persistent COGHD. © 2021, BioScientifica Ltd. All rights reserved.

Objective: To analyze metabolic parameters, body composition (BC), and bone mineral density (BMD) in childhood-onset GH deficiency (COGHD) patients during the transition period (TP). Design: Single-center, retrospective study was performed on 170 consecutive COGHD patients (age 19.2 ± 2.0 years, range 16–25) transferred after growth completion from two pediatric clinics to the adult endocrine unit. Two separate analyses were performed: (i) cross-sectional analysis of hormonal status, metabolic parameters, BC, and BMD at first evaluation after transfer from pediatrics to the adult department; (ii) longitudinal analysis of BC and BMD dynamics after 3 years of GH replacement therapy (rhGH) in TP. Results: COGHD was of a congenital cause (CONG) in 50.6% subjects, tumor-related (TUMC) in 23.5%, and idiopathic (IDOP) in 25.9%. TUMC patients had increased insulin and lipids levels (P < 0.01) and lower Z score at L-spine (P < 0.05) compared to CONG and IDOP groups. Patients treated with rhGH in childhood demonstrated lower fat mass and increased BMD compared to the rhGH-untreated group (P < 0.01). Three years of rhGH after growth completion resulted in a significant increase in lean body mass (12.1%) and BMD at L-spine (6.9%), parallel with a decrease in FM (5.2%). Conclusion: The effect of rhGH in childhood is invaluable for metabolic status, BC, and BMD in transition to adulthood. Tumor-related COGHD subjects are at higher risk for metabolic abnormalities, alteration of body composition, and decreased BMD, compared to those with COGHD of other causes. Continuation of rhGH in transition is important for improving BC and BMD in patients with persistent COGHD. © 2021, BioScientifica Ltd. All rights reserved.

(1) Background: This study aims to evaluate retinal perfusion by optical coherence tomography angiography (OCTA) in pediatric patients with type 1 diabetes mellitus (T1D) without diabetic retinopathy (DR). (2) Methods: Thirty-one patients affected by T1D were enrolled. All participants were evaluated using OCTA. The foveal avascular zone (FAZ) and superficial and deep macular vessel density (VD) were analyzed. The correlation of these parameters with metabolic factors such as body mass index (BMI), glycated hemoglobin (HbA1c), and the type of insulin therapy (multiple daily injections, MDI vs. continuous subcutaneous insulin infusion, CSII) was determined. (3) Results: None of the OCTA parameters were significantly different between the groups. The patients’ HbA1C level did not influence any of the OCTA parameters. The use of MDI tended to reduce the parafoveal and perifoveal deep VD (p = 0.048 and p = 0.021, respectively) compared to CSII. An elevated BMI tended to increase the deep macular (p = 0.005) and perifoveal VD (p = 0.006). (4) Conclusion: VD and FAZ are normal in pubescent children with T1D without signs of DR. Treatment with CSII may be a better choice compared to MDI, as CSII may be protective against retinal microvascular damage. Our results indicate the need for new clinical parameters of glycemic control in addition to HbA1c which could assess the risk of DR. © 2024 by the authors.

Background: The etiological spectrum of pituitary stalk lesions (PSL) is wide and yet specific compared to the other diseases of the sellar and suprasellar region. Because of the pituitary stalk’s (PS) critical location and role, biopsies of these lesions are rarely performed, and their underlying pathology is often a conundrum for clinicians. A pituitary MRI in association with a clinical context can facilitate their diagnosis. Aim: To present the various causes of PSL—their clinical, hormonal, histopathological, and MRI characteristics in order to gain better insight into this pathology. Method: A retrospective observational study consisting of 53 consecutive patients with PSL of the mean age 32 ± 4.2 years (range 6–67), conducted at the Department for Neuroendocrinology, Clinical Center of Serbia 2010–2018. Results: Congenital malformations were the most common cause of PSL in 25 of 53 patients (47.1%), followed by inflammatory (9/53; 16.9%) and neoplastic lesions (9/53; 16.9%). The exact cause of PSL was established in 31 (58.4%) patients, of whom 23 were with congenital PS abnormalities and 8 with histopathology of PSL (7 neoplastic and 1 Langerhans Cell Hystiocytosis). A probable diagnosis of PSL was stated in 12 patients (22.6%): 6 with lymphocytic panhypophysitis, while Rathke cleft cyst, tuberculosis, dissemination of malignancy in PS were each diagnosed in 2 patients. In 10 patients (18.8%), the etiology of PSL remained unknown. Conclusion: Due to the inability of establishing an exact diagnosis, the management and prognosis of PSL are difficult in many patients. By presenting a wide array of causes implicated in this condition, we believe that our study can aid clinicians in the challenging cases of this pathology. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

Background: The etiological spectrum of pituitary stalk lesions (PSL) is wide and yet specific compared to the other diseases of the sellar and suprasellar region. Because of the pituitary stalk’s (PS) critical location and role, biopsies of these lesions are rarely performed, and their underlying pathology is often a conundrum for clinicians. A pituitary MRI in association with a clinical context can facilitate their diagnosis. Aim: To present the various causes of PSL—their clinical, hormonal, histopathological, and MRI characteristics in order to gain better insight into this pathology. Method: A retrospective observational study consisting of 53 consecutive patients with PSL of the mean age 32 ± 4.2 years (range 6–67), conducted at the Department for Neuroendocrinology, Clinical Center of Serbia 2010–2018. Results: Congenital malformations were the most common cause of PSL in 25 of 53 patients (47.1%), followed by inflammatory (9/53; 16.9%) and neoplastic lesions (9/53; 16.9%). The exact cause of PSL was established in 31 (58.4%) patients, of whom 23 were with congenital PS abnormalities and 8 with histopathology of PSL (7 neoplastic and 1 Langerhans Cell Hystiocytosis). A probable diagnosis of PSL was stated in 12 patients (22.6%): 6 with lymphocytic panhypophysitis, while Rathke cleft cyst, tuberculosis, dissemination of malignancy in PS were each diagnosed in 2 patients. In 10 patients (18.8%), the etiology of PSL remained unknown. Conclusion: Due to the inability of establishing an exact diagnosis, the management and prognosis of PSL are difficult in many patients. By presenting a wide array of causes implicated in this condition, we believe that our study can aid clinicians in the challenging cases of this pathology. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

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. © 2019 Via Medica. All rights reserved.

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. © 2019 Via Medica. All rights reserved.