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Objective: Diabetic kidney disease (DKD) is influenced by multiple factors, yet its precise progression mechanisms remain largely unclear. This study aimed to create a clinical risk-scoring system based on genetic polymorphisms in the AFF3, CARS, CERS2, ERBB4, GLRA3, RAET1L, TMPO, and ZMIZ1 genes., Methods: The study included a DKD group diagnosed with diabetic kidney disease before age 18 and a WDC group matched by age, gender, and age at diabetes diagnosis. Genetic data and clinical data from diabetes diagnosis to moderately increased albuminuria (MIA) detection were compared between the groups., Results: Among 43 DKD cases, 22 were girls and 21 were boys. At MIA diagnosis, mean body weight SDS was -0.24 ± 0.94, height SDS was 0.34 ± 1.15, and BMI SDS was -0.26 ± 0.94. Systolic blood pressure was at the 72nd percentile (2-99), and diastolic blood pressure was at the 74th percentile (33-99). Significant differences in rs267734, rs267738, and rs942263 polymorphisms were found between DKD and non-complication diabetic groups (13[30.2 %] vs 5[11.6 %], p = 0.034; 14[32.6 %] vs 5[11.6 %], p = 0.019; 26[60.5 %] vs 40[93 %], p < 0.001)., Conclusion: Several factors were identified as significant in DKD onset, including low follow-up weight SDS, elevated diastolic blood pressure, presence of rs267734, and absence of rs942263 polymorphisms. The model demonstrated a specificity of 81.4 % and a sensitivity of 74.4 %., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ferda Evin reports financial support, article publishing charges, statistical analysis, and writing assistance were provided by Ege University Scientific Research Projects. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Spondylo-epimetaphyseal dysplasia-aggregan (SEMD-ACAN) is a rare form of osteo-chondrodysplasia that includes vertebral, epiphyseal and metaphyseal dysplasia. It occurs as a result of loss-of-function mutations in the ACAN gene, which encodes aggregan protein, which is the basic component of the extracellular matrix in cartilage. It results in disproportionately short stature and skeletal abnormalities. Here, we aimed to present the fourth SEMD-ACAN report in the literature., Case Presentation: A 9-year-old girl was admitted to our clinic with growth retardation. She was born from a first-degree cousin marriage with severe short stature (41 cm; -3.54 SDS). Her mother also had severe short stature. Her height was 110 cm (-4.6 SDS); she had midface hypoplasia, low-set ears, short neck, short limbs, and central obesity. Biochemical and hormonal tests were normal. Skeletal survey showed moderate platyspondylia, thoracolumbar scoliosis, lumbar lordosis, bilateral femoro-acetabular narrowing, and advanced bone age (10 years). The patient's brother was 100 cm (-3.97 SDS). He had similar but milder clinical findings. Biallelic ACAN variation (c.512C>T; p. Ala171Val) was detected in two siblings by next-generation sequencing. The parents were heterozygous carriers. Before, the heterozygous form of this variant has been reported in a 15-year-old boy with short stature, advanced bone age, and dysmorphic features., Conclusions: SEMD-ACAN is a rare genetic condition that affects bone growth and development and can cause physical and developmental abnormalities. This article highlights the importance of considering genetic testing in characteristic symptoms associated with SEMD-ACAN, such as severe growth retardation and skeletal abnormalities., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: Nuclear receptor subfamily 5 group A member 1 ( NR5A1 ) is a transcription factor critical for the development of various organs. Pathogenic variants in NR5A1 are associated with a spectrum of disorders of sex development (DSD)., Case Presentation: A 15-month-old baby, raised as a girl, was referred for genital swelling and ambiguous genitalia. Born to healthy consanguineous parents, the baby had a phallus, perineal hypospadias, labial fusion, and a hypoplastic scrotum. Hormonal evaluation showed normal levels, and ultrasonography revealed small gonads and absence of Müllerian derivatives. Post-human chorionic gonadotropin (hCG) testing indicated an adequate testosterone response. The karyotype was 46,XY, and in it was found a homozygous NR5A1 variant (c.307 C>T, p.Arg103Trp) in a custom 46 XY DSD gene panel. Notably, the patient exhibited complete sex reversal, hyposplenia, and no adrenal insufficiency., Conclusions: Previously, NR5A1 pathogenic variants were considered to be dominantly inherited, and homozygous cases were thought to be associated with adrenal insufficiency. Despite the homozygous pathogenic variant, our patient showed hyposplenism with normal adrenal function; this highlights the complexity of NR5A1 genotype-phenotype correlations. These patients should be monitored for adrenal insufficiency and DSD as well as splenic function., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: Advanced glycation end products (AGEs) are irreversible macromolecules formed by nonenzymatic reactions due to chronic hyperglycemia. The aim of this study was to assess the relationship between AGEs and the microvascular complications of children and adolescents with type 1 diabetes mellitus (T1DM)., Materials and Methods: Twenty-six T1DM patients with microvascular complications and 58 complication-naive patients who were similar regarding age, sex, and pubertal status enrolled in the study. Anthropometric, biochemical, ophthalmologic, and neurologic variables were compared with serum AGEs levels by the fluorescence method., Results: There was no significant difference observed between the patients with complications and those without complications in terms of serum levels of AGEs and other biochemical parameters. However, the duration of T1DM and urine microalbumin-creatinine ratio (uACR) were significantly higher in the complication-positive group (P < .001). Serum levels of AGEs were found to be similar when retinopathy, peripheral, and optic neuropathy were separately compared with the complication-naive group (P > .05). However, patients with nephropathy had significantly higher serum levels of AGEs than patients without complications (P = .023). In addition, there was a significant positive correlation between serum AGEs levels and uACR (P = .042) but not other parameters (P > .05)., Conclusion: This study is the first to evaluate the association between serum AGEs levels and microvascular complications in children and adolescents with T1DM. Our study highlights that serum AGEs levels are significantly correlated with nephropathy but not with retinopathy and neuropathy. Further long-term studies with a larger sample size are required to establish a better relationship between diabetic complications and AGEs. Cite this article as: Kırkgöz T, Acar S, Küme T, et al. Evaluation of serum advanced glycation end product levels and microvascular complications in children and adolescents with type 1 diabetes mellitus. Turk Arch Pediatr. 2024;59(1):31-37.

Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH., Materials and Methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed., Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR., Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.

Objectives: Central precocious puberty (CPP) develops as a result of early stimulation of the hypothalamic-pituitary-gonadal (HPG) axis. The loss-of-function mutations in the Makorin-ring-finger3 (MKRN3) gene appear to be the most common molecular cause of familial CPP. We aimed to identify MKRN3 gene mutations in our CPP cohort and to investigate the frequency of MKRN3 mutations., Methods: 102 patients with CPP included. 53 of them had family history of CPP in the first and/or second-degree relatives. MKRN3 gene was analyzed by next-generation sequencing., Results: Possible pathogenic variants were found in 2/53 patients with family history of CPP (3.8%) and 1/49 patient without family history (2%). A novel heterozygous c.1A>G (p.Met1Val) mutation, a novel heterozygous c.683&#95;684delCA (p.Ser228*) and a previously reported c.482dupC (Ala162Glyfs*) frameshift variations were detected. The two novel variants are predicted to be pathogenic in silico analyses., Conclusions: In our cohort, possible pathogenic variants in MKRN3 gene were detected in 2.9% of the total cohort, 3.8% of the familial and 2% of the nonfamilial cases, slightly lower than that reported in the literature. Two novel variants detected contribute to the molecular repertoire of MKRN3 defects in CPP. Classical pattern of paternal inheritance has been demonstrated in all three cases. However, the father of the patient 3 did not have history of CPP suggesting that the father inherited this variant from his mother and had phenotype skipping. Therefore, we emphasize that the absence of history of CPP in the father does not exclude the possibility of a MKRN3 mutation., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Dysosteosclerosis (DOS) is a rare sclerosing bone dysplasia characterized by unique osteosclerosis of the long tubular bones and platyspondyly. DOS is inherited in an autosomal recessive manner and is genetically and clinically heterogeneous. To date, four individuals with DOS who have five different TNFRSF11A mutations have been reported. Based on their data, it is hypothesized that mutations producing aberrant mutant RANK proteins (missense or truncated or elongated) cause DOS, while null mutations lead to osteopetrosis, autosomal recessive 7 (OPTB7). Herein, we present the fifth case of TNFRSF11A -associated DOS with a novel homozygous frame-shift mutation (c.19&#95;31del; p.[Arg7CysfsTer172]). The mutation is predicted to cause nonsense mutation-mediated mRNA decay (NMD) in all RANK isoform transcripts, resulting in totally null allele. Our findings suggest genotype-phenotype relationship in TNFRSF11A -associated OPTB7 and DOS remains unclear, and that the deficiency of TNFRSF11A functions might cause DOS, rather than osteopetrosis. More data are necessary to understand the phenotypic spectrum caused by TNFRSF11A mutations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kırkgöz, Özkan, Hazan, Acar, Nalbantoğlu, Özkaya, Kulalı, Gürsoy, Ikegawa and Guo.)

Objective: To evaluate the efficacy of degludec/aspart (IDegAsp) insulin co-formulation in children and adolescents with poorly controlled type 1 diabetes (T1DM)., Methods: Patients with poorly controlled T1DM on basal-bolus insulin regimes and having compliance problems related to insulin injections were switched to IDegAsp and were included. Data on hemoglobin A1c (HbA1c) levels, hypoglycemic episodes, frequency of diabetic ketoacidosis (DKA) and insulin doses were recorded at baseline and after one year of IDegAsp treatment., Results: Fifty patients (22 girls; 44%) were started on IDegAsp. The mean±standard deviation (range) age and duration of diabetes were 12.9±3.4 (4-18) and 5.2±3.1 (1.0-13.7) years, respectively. At the end of one year, 38 patients were still on IDegAsp, whereas 12 patients had opted to resume their original treatments. In those who continued on IDegAsp, HbA1c levels did not change, but the number of self-reported mild-moderate hypoglycemic episodes decreased significantly (p<0.05). In the year before switching to IDegAsp, 11 DKA attacks in 9 patients were observed, whereas this decreased to 4 DKA attacks in 4 patients after one year of IDegAsp therapy (p=0.06)., Conclusion: IDegAsp regimen may improve clinical management in poorly controlled basal-bolus insulin regimen T1DM patients who have frequent hypoglycemia and DKA attacks, as well as in those with poor compliance with multiple injections. Although a simplified basal-bolus IDegAsp regimen is an attractive option for patients with T1DM, some may not adapt to this treatment due to the fixed IAsp dose of IDegAsp.

The novel coronavirus disease (COVID-19) has emerged as a global pandemic. This was a prospective, case-control study conducted in Izmir, Turkey. The aim of this study was to assess the relationship between COVID-19 and new-onset T1DM. We included pediatric patients (aged 6 mo-18 yr) with new-onset type-1 diabetes mellitus (T1DM) diagnosed during the COVID-19 pandemic, between April 2020 and January 2021. Polymerase chain reaction was used to diagnose COVID-19 after hospital admission. An enzyme-linked immunoassay for IgM and IgG against SARS-CoV-2 was performed after the diagnosis was confirmed. In the control group, the blood antibody test was conducted as close as possible to the time of the T1DM patient referral. A total of 118 participants were included in the study, comprising 57 (48%) patients with new-onset T1DM and 61 (52%) healthy controls. Of the 57 patients, 36 (63.2%) presented with DKA, 17 (29.7%) with diabetic ketosis, and four (7%) incidentally. The SARS-CoV-2 antibody test was positive in five (8.7%) patients with T1DM and six (10%) controls. The rate of positivity did not differ between the two groups (p = 0.901). It was not possible to demonstrate a clear association between SARS-CoV-2 infection and new-onset T1DM. Whether SARS-CoV-2 increases susceptibility to diabetes by triggering islet cell autoimmunity and affects the timing of overt diabetes in patients with existing autoimmunity should be studied in large cohorts., Competing Interests: None of the authors have any potential conflicts of interest associated with this research., (2022©The Japanese Society for Pediatric Endocrinology.)

Background. Acute otitis media [AOM] may affect the accuracy of tympanic temperature measurements. We aimed to compare tympanic temperature measurements in patients with AOM against control groups, as well as compare the tympanic temperatures with axillary thermometry. Methods. This is a prospective, observational study. Patients from pediatric outpatient and emergency clinics who were diagnosed as single-sided AOM were included consecutively in the study. Normal ears of patients and children having the same age and gender who were not diagnosed as AOM were also studied as controls. Results. In patients with AOM, infected ears had higher temperatures than normal ears with a mean of 0.48 ± 0.01°C. There was no significant difference between the right and left tympanic temperatures in control group. Compared with axillary temperature, the sensitivity of tympanic temperature in the infected ear was 91.7% and the specificity was 74.8%. Conclusion. Comparisons of axillary and tympanic temperatures in children with AOM during the active infection concluded higher tympanic temperatures in infected ears. We suggest that the higher tympanic temperatures, approximately 0.5°C in our study, in infected ears may aid in diagnosis of patients with fever without a source in pediatric clinics.