Childhood obesity accelerates biological ageing: is oxidative stress a link?

Obesity is a multifactorial pathophysiological condition with an imbalance in biochemical, immunochemical, redox status and genetic parameters values. We aimed to estimate the connection between relative leucocyte telomere lengths (rLTL) - biomarker of cellular ageing with metabolic and redox status biomarkers values in a group of obese and lean children. The study includes 110 obese and 42 lean children and adolescents, both sexes. The results suggested that rLTL are significantly shorter in obese, compared with lean group (P < 0·01). Negative correlation of rLTL with total oxidant status (TOS) (Spearman's ρ = -0·365, P < 0·001) as well as with C-reactive protein (Spearman's ρ = -0·363, P < 0·001) were observed. Principal component analysis (PCA) extracted three distinct factors (i.e. principal components) entitled as: prooxidant factor with 35 % of total variability; antioxidant factor with 30 % of total variability and lipid antioxidant - biological ageing factor with 12 % of the total variability. The most important predictor of BMI > 30 kg/m2 according to logistic regression analysis was PCA-derived antioxidant factor's score (OR: 1·66, 95th Cl 1·05-2·6, P = 0·029). PCA analysis confirmed that oxidative stress importance in biological ageing is caused by obesity and its multiple consequences related to prooxidants augmentation and antioxidants exhaustion and gave us clear signs of disturbed cellular homoeostasis deepness, even before any overt disease occurrence.

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%).

Single center study of 53 consecutive patients with pituitary stalk lesions.

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.

Neonatal Outcome in Pregnancies with Autoimmune Myasthenia Gravis.

INTRODUCTION: Acquired autoimmune myasthenia gravis (MG) is an autoimmune process in which antibodies (AB) directed against the acetylcholine nicotinic receptor (AChR) cause weakness and fatigue of striated muscles. OBJECTIVES: The objective of this study was to determine the range of clinical manifestations in newborns with transient neonatal myasthenia (TNM). METHODS: 62 newborns with mothers who had autoimmune MG were followed by: anthropometric parameters, gestational age, gender, type of delivery completion, Apgar score (AS) in the first and fifth minute, and the emergence of TNM symptoms. RESULTS: For fourteen consecutive years, from a total of 98,000 infants, 62 (0.06%) were born to mothers with autoimmune MG. Four of them (6.4%) had symptoms of TNM. CONCLUSION: Newborns of mothers with MG manifest clinical features of TNM relative to stage of mother's illness. These newborns need monitoring until the seventh day of life.

Circulating Fatty Acids Associate with Metabolic Changes in Adolescents Living with Obesity.

Fatty acids play a crucial role in obesity development and in the comorbidities of obesity in both adults and children. This study aimed to assess the impact of circulating fatty acids on biomarkers of metabolic health of adolescents living with obesity. Parameters such as blood lipids, redox status, and leukocyte telomere length (rLTL) were measured alongside the proportions of individual fatty acids. The Mann-Whitney U test revealed that individuals with obesity exhibited an unfavorable lipid and redox status compared to the control normal weight group. The group with obesity also had lower plasma n-3 polyunsaturated fatty acids (PUFAs) and a higher ratio of n-6 to n-3 PUFAs than the control group. They also had a shorter rLTL, indicating accelerated biological aging. There was an inverse association of rLTL and plasma n-6-to-n-3 PUFA ratio. Future studies should explore the impact of recommended nutrition plans and increased physical activity on these parameters to determine if these interventions can enhance the health and well-being of adolescents with obesity, knowing that early obesity can track into adulthood.

Retinal Perfusion Analysis of Children with Diabetes Mellitus Type 1 Using Optical Coherence Tomography Angiography.

(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.

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.

Neonatal diabetes mellitus due to a new KCNJ11 mutation - 10 years of the patient`s follow-up.

BACKGROUND: Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-sensitive potassium channel, often result in neonatal diabetes. CASE: In this report, we describe a 10-year-old girl who is heterozygous for a new missense mutation in the KCNJ11 gene and whose treatment was successfully switched from insulin to sulfonylurea (glibenclamide) therapy when she was one month old. 10-year data on a low-dose of glibenclamide monotherapy showed excellent glycaemic control with no reports of severe hypoglycaemia and microvascular complications. CONCLUSION: An early genetic diagnosis of neonatal diabetes mellitus is highly beneficial because early switch from insulin to sulfonylurea is safe, avoids unnecessary insulin therapy and promotes sustained improvement of glycaemic control on long-term follow-up.

Mapping the journey of transition: a single-center study of 170 childhood-onset GH deficiency patients.

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.

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.

Duration of valproic acid monotherapy correlates with subclinical thyroid dysfunction in children with epilepsy.

To identify potential risk factors for the development of subclinical hypothyroidism following long-term valproic acid monotherapy in children with epilepsy. Serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine, thyreoglobulin antibodies, and thyroid peroxidase antibodies were determined in 41 patients and in 41 sex- and age-matched healthy children. Mean valproic acid treatment duration was 2.80±1.96 years. The valproic acid group had higher serum thyroid-stimulating hormone (p<0.001) and free triiodothyronine (p<0.05) levels compared to the control group. Serum thyroid-stimulating hormone and free triiodothyronine were above the upper limit for healthy controls in 34% and 32% of patients, respectively, and no clinical features of thyroid dysfunction were observed. Duration of valproic acid monotherapy for less than four years was a risk factor for elevated thyroid-stimulating hormone levels. One third of children with normal range serum valproic acid levels may have elevated serum thyroid-stimulating hormone and free triiodothyronine levels, especially in the first four years of treatment.

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.

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.

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.

Reference values of capillary blood saturation in neonates and its difference from pulse oximetry.

INTRODUCTION: Haemoglobin saturation is an obligatory oxygen parameter in the assessment of neonatal oxygenation. Although, pulse oximetry is currently one of the major methods in the determination of haemoglobin saturation, capillary blood saturation is still present in the diagnostic process. As well known, haemoglobin saturation value of capillary blood is insufficiently accurate, but not as much as the difference in relation to the values determined by pulse oximetry. Until now published studies have reported that capillary samples are obtained according to a protocol by the principle of free blood outflow, which is practically almost unachievable in the neonate. OBJECTIVE: Determination of the reference values of oxygen saturation (SCO2) and partial pressure (pcO2) of capillary blood by squeezing of the foot. The determination of difference between ScO2 and pulse oximetry (SpO2). METHODS: In 134 term newborns, we determined SpO2. Subsequently, we measured the values of ScO2 and pcO2 from the same extremity. While withdrawing a capillary sample, we exerted multiple squeezing of the foot. The mean value of ScO2, pcO2, SpO2 and the difference between ScO2 and SpO2 were determined. RESULTS: Mean ScO2 value was 80.5 +/- 8.5%, pcO2 was 48.2 +/- 11.4 mm Hg and SpO2 was 98 +/- 1.9%. The difference between ScO2 and SpO2 values was 17.5 +/- 8.6% (t = 23.568; p = 0.000). CONCLUSION: There is a statistically highly significant difference between the values of ScO2 and SpO2. Having the knowledge of this difference can increase the accuracy of clinical evaluation and further diagnostics. Comparison in up-to-now conducted studies suggests that the squeezing of the foot for obtaining a capillary sample in relation to free blood outflow does not bear any significant influence on the resultant values of haemoglobin saturation.

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.