INTRODUCTION: Thyroid surgery in children is a rare operation. The aim of our paper is to point out the specifics of thyroid surgery in children. METHODS: Retrospective analysis of patients hospitalized at the Department of Paediatric Surgery, Faculty of Medicine, Comenius University and National Institute of Childrens Diseases in Bratislava during a 10-year period (20072016) who underwent thyroid surgeries. RESULTS: The retrospective analysis included 81 patients: 66 (81%) girls and 15 (19%) boys. The mean age of the patients was 14 years ±8 months (range 418 years). The most common indications for thyroid surgery were: a nodule in 36 (44.4%) patients, Graves Basedow thyrotoxicosis in 19 (23.5%) patients, and suspected thyroid carcinoma in 11 (13.6%) patients. Cervical lymph node metastases (mts) were diagnosed in 9 (11.1%) patients, and distant pulmonary metastases in 5 (6.17%) patients. Total thyroidectomy (TTE) was performed in 43 (53%) patients, total lobectomy (TL) in 20 (24.7%) patients. Extended surgery on regional lymph nodes was performed in 9 (11.1%) patients. Eight (9.9%) patients underwent reoperation. A total of 12 (14.8%) patients experienced postoperative complications. Unilateral transient recurrent laryngeal nerve (RLN) paralysis occurred in 2 patients, and permanent in one patient. Transient postoperative hypoparathyroidism with hypocalcaemia was reported in 8 (9.9%) patients; no permanent condition of this type was observed. CONCLUSION: Multidisciplinary collaboration ensures that optimal surgical results are achieved in the patients. Experience of the surgeon performing thyroid surgery in children remains crucial.

• Klíčová slova
• thyroid gland − thyroid carcinoma, thyroidectomy − NLR paresis − node in children,
• MeSH
• dítě MeSH
• lidé MeSH
• nádory štítné žlázy * chirurgie   MeSH
• ochrnutí hlasivek * MeSH
• pooperační komplikace MeSH
• retrospektivní studie MeSH
• tyreoidektomie škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Heterozygous inactivating mutations of the glucokinase (GCK) gene are causing GCK-MODY, one of the most common forms of the Maturity Onset Diabetes of the Young (MODY). GCK-MODY is characterized by fasting hyperglycemia without apparent worsening with aging and low risk for chronic vascular complications. Despite the mild clinical course, GCK-MODY could be misdiagnosed as type 1 or type 2 diabetes. In the diagnostic process, the clinical suspicion is often based on the clinical diagnostic criteria for GCK-MODY and should be confirmed by DNA analysis. However, there are several issues in the clinical and also in genetic part that could complicate the diagnostic process. Most of the people with GCK-MODY do not require any pharmacotherapy. The exception are pregnant women with a fetus which did not inherit GCK mutation from the mother. Such a child has accelerated growth, and has increased risk for diabetic foetopathy. In this situation the mother should be treated with substitutional doses of insulin. Therefore, distinguishing GCK-MODY from gestational diabetes in pregnancy is very important. For this purpose, special clinical diagnostic criteria for clinical identification of GCK-MODY in pregnancy are used. This review updates information on GCK-MODY and discusses several currently not solved problems in the clinical diagnostic process, genetics, and treatment of this type of monogenic diabetes.

• MeSH
• diabetes mellitus 2. typu enzymologie   genetika   patologie   MeSH
• glukokinasa genetika   metabolismus   MeSH
• heterozygot MeSH
• hyperglykemie enzymologie   genetika   patologie   MeSH
• lidé MeSH
• mutace * MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• glukokinasa MeSH

MEHMO syndrome is a rare X-linked syndrome characterized by Mental retardation, Epilepsy, Hypogenitalism, Microcephaly, and Obesity associated with the defect of protein synthesis caused by the EIF2S3 gene mutations. We hypothesized that the defect in protein synthesis could have an impact on the immune system. We describe immunologic phenotype and possible treatment outcomes in patient with MEHMO syndrome carrying a frame-shift mutation (I465fs) in the EIF2S3 gene. The proband (currently 9-year-old boy) had normal IgG and IgM levels, but had frequent respiratory and urinary tract infections. On subcutaneous immunoglobulin therapy achieving supra-physiological IgG levels the frequency of infections significantly decreased in Poisson regression by 54.5 % (CI 33.2-89.7, p=0.017). The MEHMO patient had had frequent acute infections despite normal IgG and IgM serum levels and responded well to the immunoglobulin treatment.

• MeSH
• dítě MeSH
• epilepsie farmakoterapie   genetika   imunologie   patologie   MeSH
• eukaryotický iniciační faktor 2 genetika   MeSH
• fenotyp MeSH
• hypogonadismus farmakoterapie   genetika   imunologie   patologie   MeSH
• lidé MeSH
• mentální retardace vázaná na chromozom X farmakoterapie   genetika   imunologie   patologie   MeSH
• mikrocefalie farmakoterapie   genetika   imunologie   patologie   MeSH
• mutace * MeSH
• obezita farmakoterapie   genetika   imunologie   patologie   MeSH
• pohlavní orgány abnormality   imunologie   patologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• EIF2S3 protein, human MeSH Prohlížeč
• eukaryotický iniciační faktor 2 MeSH

Recently, the genetic cause of several syndromic forms of glycemia dysregulation has been described. One of them, MEHMO syndrome, is a rare X-linked syndrome recently linked to the EIF2S3 gene mutations. MEHMO is characterized by Mental retardation, Epilepsy, Hypogonadism/hypogenitalism, Microcephaly, and Obesity. Moreover, patients with MEHMO had also diabetes and endocrine phenotype, but detailed information is missing. We aimed to provide more details on the endocrine phenotype in two previously reported male probands with MEHMO carrying a frame-shift mutation (I465fs) in the EIF2S3 gene. Both probands had a neonatal hypoglycemia, early onset insulin-dependent diabetes, and hypopituitarism due to dysregulation and gradual decline of peptide hormone secretion. Based on the clinical course in our two probands and also in previously published patients, neonatal hypoglycemia followed by early-onset diabetes and hypopituitarism may be a consistent part of the MEHMO phenotype.

• MeSH
• diabetes mellitus 1. typu vrozené   genetika   MeSH
• endokrinní žlázy metabolismus   MeSH
• epilepsie genetika   MeSH
• eukaryotický iniciační faktor 2 genetika   MeSH
• fenotyp MeSH
• hypoglykemie vrozené   genetika   MeSH
• hypogonadismus genetika   MeSH
• hypopituitarismus vrozené   genetika   MeSH
• lidé MeSH
• mentální retardace vázaná na chromozom X genetika   MeSH
• mikrocefalie genetika   MeSH
• novorozenec MeSH
• obezita genetika   MeSH
• pohlavní orgány abnormality   MeSH
• posunová mutace MeSH
• transkripční faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• EIF2S3 protein, human MeSH Prohlížeč
• Eif2s3y protein, mouse MeSH Prohlížeč
• eukaryotický iniciační faktor 2 MeSH
• transkripční faktory MeSH

BACKGROUND: Therapy with sulfonylurea is preferable to insulin in the majority of individuals with KCNJ11 mutations, but not all of these people achieve target levels of HbA1c in long-term follow-up. We aimed to compare sulfonylurea therapy with insulin treatment in two sulfonylurea-sensitive individuals with a KCNJ11 mutation who had poorly controlled permanent neonatal diabetes mellitus. CASE REPORT: We report on two individuals with a KCNJ11 mutation (p.R201H) who are currently aged 35 (SVK1) and 21 years (SVK2). These individuals were switched from insulin to sulfonylurea in 2005. Data from the first 4 (SVK2) and 8 years (SVK1) of the follow-up showed improved diabetes control and increased quality of life for both individuals. During the following years, however, both individuals failed to retain good diabetes control (HbA1c ≤ 53 mmol/mol; 7.0%). We therefore changed the therapy to a combination of insulin and sulfonylurea in both individuals, or to insulin monotherapy in SVK1, and compared the effects on HbA1c with those of sulfonylurea monotherapy. HbA1c levels in both individuals worsened after adding insulin to sulfonylurea [67 mmol/mol (8.3%) vs 77 mmol/mol (9.2%) in SVK1 and 106 mmol/mol (11.8%) vs 110±19 mmol/mol (12.2±1.7%) in SVK2], and after switching to only insulin therapy in SVK1 [57 mmol/mol (7.4%) vs 62 mmol/mol (7.8%)] when compared with sulfonylurea monotherapy. DISCUSSION: Our data show that sulfonylurea monotherapy might be preferable to insulin in people with permanent neonatal diabetes mellitus sensitive to sulfonylurea even when HbA1c is above target.

• MeSH
• diabetes mellitus krev   farmakoterapie   genetika   MeSH
• dospělí MeSH
• draslíkové kanály dovnitř usměrňující genetika   MeSH
• glibenklamid terapeutické užití   MeSH
• glykovaný hemoglobin metabolismus   MeSH
• hypoglykemika terapeutické užití   MeSH
• inzulin terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• mladý dospělý MeSH
• mutace genetika   MeSH
• náhrada léků MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• draslíkové kanály dovnitř usměrňující MeSH
• glibenklamid MeSH
• glykovaný hemoglobin MeSH
• hypoglykemika MeSH
• inzulin MeSH
• Kir6.2 channel MeSH Prohlížeč

Familial hypercholesterolemia (FH) is most frequently caused by LDLR or APOB mutations. Therefore, the aim of our study was to examine the genetic background of Slovak patients suspected of FH. Patients with clinical suspicion of FH (235 unrelated probands and 124 family relatives) were recruited throughout Slovakia during the years 2011-2015. The order of DNA analyses in probands was as follows: 1. APOB mutation p.Arg3527Gln by real-time PCR method, 2. direct sequencing of the LDLR gene 3. MLPA analysis of the LDLR gene. We have identified 14 probands and 2 relatives with an APOB mutation p.Arg3527Gln, and 89 probands and 75 relatives with 54 different LDLR mutations. Nine of LDLR mutations were novel (i.e. p.Asp90Glu, c.314-2A>G, p.Asp136Tyr, p.Ser177Pro, p.Lys225_Glu228delinsCysLys, p.Gly478Glu, p.Gly675Trpfs*42, p.Leu680Pro, p.Thr832Argfs*3). This is the first study on molecular genetics of FH in Slovakia encompassing the analysis of whole LDLR gene. Genetic etiology of FH was confirmed in 103 probands (43.8 %). Out of them, 86.4 % of probands carried the LDLR gene mutation and remaining 13.6 % probands carried the p.Arg3527Gln APOB mutation.

• MeSH
• dospělí MeSH
• hyperlipoproteinemie typ II diagnóza   epidemiologie   genetika   MeSH
• kvantitativní polymerázová řetězová reakce metody   MeSH
• lidé MeSH
• mladý dospělý MeSH
• receptory LDL genetika   MeSH
• statistika jako téma metody   MeSH
• zdravotnické přehledy * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika epidemiologie   MeSH
• Názvy látek
• LDLR protein, human MeSH Prohlížeč
• receptory LDL MeSH

OBJECTIVES: The mutations in gene for the melanocortin-4 receptor (MC4R) are the most common etiology factors of monogenic obesity development. Recently, it has been shown that current life style has a significant impact on the phenotype of MC4R mutation carriers - increases the penetrance of the mutations. We aimed to study the impact of the current age on the time of obesity onset among MC4R mutation carriers. METHODS: DNA analysis of the MC4R gene was performed in 268 unrelated Slovak and Moravian obese children and adolescents 18 years and 28 blood relatives >18 years of the probands with a mutation. RESULTS: Three different previously described heterozygous loss of function MC4R mutations (p.Ser19Alafs*34, p.Ser127Leu, and p.Gly181Asp) were found in 3 <18 years probands, 3 adult probands, and 6 adult obese/overweight family relatives. The age of obesity onset in mutation carriers was 1 year in all probands in the children group and 1-35 years (median 11 years) in adults. The age of the obesity onset significantly correlated (R=0.809, p=0.028) with the current age in all of the MC4R mutation carriers. CONCLUSIONS: The age of obesity onset in the present child generation of MC4R mutation carriers is decreasing compared to the age of onset in their parents' generation. This is in agreement with similarly increasing penetrance of obesity in MC4R mutation carriers and it points out to escalation of obesogenic potential of environment.

• Klíčová slova
• MC4R mutation carriers, adolescents., children, obesity,
• MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie MeSH
• heterozygot MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace * MeSH
• mutační analýza DNA MeSH
• obezita dětí a dospívajících diagnóza   epidemiologie   genetika   MeSH
• předškolní dítě MeSH
• receptor melanokortinový typ 4 genetika   MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Slovenská republika epidemiologie   MeSH
• Názvy látek
• MC4R protein, human MeSH Prohlížeč
• receptor melanokortinový typ 4 MeSH

The most common etiology of non-syndromic monogenic obesity are mutations in gene for the Melanocortin-4 receptor (MC485) with variable prevalence in different countries (1.2-6.3 % of obese children). The aim of our study was 1) to search for MC4R mutations in obese children in Slovakia and compare their prevalence with other European countries, and 2) to describe the phenotype of the mutation carriers. DNA analysis by direct Sanger sequencing of the coding exons and intron/exon boundaries of the MC4R gene was performed in 268 unrelated Slovak children and adolescents with body mass index above the 97(th) percentile for age and sex and obesity onset up to 11 years (mean 4.3+/-2.8 years). Two different previously described heterozygous loss of function MC4R variants (i.e. p.Ser19Alafs*34, p.Ser127Leu) were identified in two obese probands, and one obese (p.Ser19Alafs*34), and one lean (p.Ser127Leu) adult family relatives. No loss of function variants were found in lean controls. The prevalence of loss-of-function MC4R variants in obese Slovak children was 0.7 %, what is one of the lowest frequencies in Europe.

• MeSH
• dítě MeSH
• fenotyp MeSH
• genotyp MeSH
• heterozygot MeSH
• lidé MeSH
• mladiství MeSH
• mutační analýza DNA MeSH
• obezita dětí a dospívajících genetika   MeSH
• předškolní dítě MeSH
• receptor melanokortinový typ 4 genetika   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Slovenská republika MeSH
• Názvy látek
• MC4R protein, human MeSH Prohlížeč
• receptor melanokortinový typ 4 MeSH

Monogenic diabetes mellitus is a type of diabetes, where genetics without any other factors is strong enough to cause the disease. According to the clinical features monogenic diabetes can be divided to the mild familial early onset diabetes, familial fasting hyperglycemia, diabetes with extrapancreatic features and neonatal diabetes mellitus. During the last several years the number of genes causing monogenic diabetes has continuously increased. The clinical picture of the monogenic diabetes is very heterogeneous, thus DNA analysis is required for identification of the diabetes etiology, which influences also the choice of treatment. This article is an overview of current knowledge on monogenic diabetes, focusing at the clinically and epidemiologically most important forms.

• MeSH
• diabetes mellitus genetika   MeSH
• komplikace diabetu genetika   MeSH
• lidé MeSH
• mutace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

High prevalence of obesity in all of age categories is currently one of the biggest problem in medicine. Identification of etiology of obesity can individualise an approach to the patient and it is essential for choosing a target management and therapy. Beside the largest group with polygenic inheritance are clinically important also patients with "syndromic obesity", where obesity is only one of the signs and monogenic obesity, where obesity is the major clinical phenotype (patients with mutations in gene for leptin, leptine receptor, prohormone convertase 1, melanocortine receptor 4, brain-derived neurotropic factor and tyrosin kinase receptor B). The monogenic obesity includes 3-4% of all patients with obesity. This review article brings newest insight on genetics, clinical manifestation, diagnostics and therapy of these diseases.

• MeSH
• leptinové receptory genetika   MeSH
• lidé MeSH
• mozkový neurotrofický faktor genetika   MeSH
• mutace MeSH
• obezita genetika   MeSH
• pro-opiomelanokortin genetika   MeSH
• proproteinkonvertasy genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• leptinové receptory MeSH
• mozkový neurotrofický faktor MeSH
• pro-opiomelanokortin MeSH
• proproteinkonvertasy MeSH