Agnieszka Zubkiewicz-Kucharska

Background: SPATA5L1-related neurodevelopmental disorder is a recently described condition characterized by psychomotor delay, sensorineural hearing loss, and variable motor dysfunction. Because only a few cases have been reported, the full phenotypic spectrum remains poorly defined. Expanding clinical characterization is crucial for improving early diagnosis and targeted management. Case Presentation: We report a 24-month-old female with compound heterozygous SPATA5L1 variants c.1918C>T (p.Arg640Ter) and c.2066G>T (p.Gly689Val). She presented with global psychomotor delay, bilateral sensorineural hearing loss, strabismus, and craniofacial dysmorphism. Brain MRI showed cortical and white matter atrophy, delayed myelination, and a thin corpus callosum. Vojta neurodevelopmental assessment demonstrated an 11-month motor delay, abnormal responses in all seven Vojta postural reactions, and persistent primitive reflexes. Early EEG recordings were without significant changes, whereas abnormalities emerged later in the clinical course. Genetic testing confirmed the variants in trans. Management and Outcomes: Early rehabilitation including reflex locomotion therapy was initiated. The persistence of primitive reflexes, central hypotonia, and pathological postural reactions provided a coherent neuromotor profile and indicated a high vulnerability to atypical motor development, and do not rule out the possibility of later evolution toward a spastic–dystonic motor pattern. These findings, combined with neuroimaging abnormalities, refined the patient’s neuromotor phenotype and guided individualized therapeutic planning. Conclusions: This case expands the clinical and neurodevelopmental spectrum associated with SPATA5L1 variants and highlights the diagnostic value of integrating genomic sequencing with structured motor assessments. Early, multidimensional evaluation may improve recognition of rare neurodevelopmental disorders and support more precise prognostication and rehabilitation strategies.

Hypergonadotropic hypogonadism is usually caused by the impairment of the structure and function of the gonads, but there are cases caused by reduced stimulation by the follicle-stimulating hormone (FSH) as a result of abnormal variants of genes encoding the follicle-stimulating hormone or its receptor (FSHR). We present the case of an elite athlete with the c.2039A>G variant in one allele of the FSHR gene resulting in hypergonadotropic hypogonadism, low testicular volume, and reduced semen parameters, placing particular emphasis on the diagnostic process and the importance of correct diagnosis in the context of possible treatment with gonadotropins, which can significantly improve fertility, increase testosterone levels, and, in the case of athletes, obtain approval from the anti-doping organization for treatment that increases testosterone levels.

Obesity often coexists with thyroid diseases, and the prevalence of these disorders has been on the rise for years. While hypothyroidism can contribute to excess fat tissue, the relationship between Body Mass Index (BMI) and thyroid function hormones is bidirectional. Research confirms that fat tissue reduction can positively impact thyroid function. Thus, delaying the initiation of therapies beyond substitution treatment to achieve optimal weight reduction in individuals with thyroid dysfunction seems unwarranted. The authors summarize current knowledge on this topic in the article.

Obesity often coexists with thyroid diseases, and the prevalence of these disorders has been on the rise for years. While hypothyroidism can contribute to excess fat tissue, the relationship between Body Mass Index (BMI) and thyroid function hormones is bidirectional. Research confirms that fat tissue reduction can positively impact thyroid function. Thus, delaying the initiation of therapies beyond substitution treatment to achieve optimal weight reduction in individuals with thyroid dysfunction seems unwarranted. The authors summarize current knowledge on this topic in the article.

The impact of obesity on kidney injury and the development of chronic kidney disease (CKD) is well documented. Unfortunately, the early stages of CKD are asymptomatic, leading to a delayed diagnosis and a worse prognosis. There is a need for more sensitive indicators of kidney damage than those currently used. We aimed to assess the usefulness of serum t-CAF, urinary netrin-1, α-GST, π-GST, calbindin, and calprotectin as biomarkers of early kidney damage in obese children and to investigate the relationship between these indicators and the degree of obesity. A total of 125 simple obese, normoalbuminuric children and 33 non-obese children as controls were selected. Patients were divided into 2 subgroups according to SDS BMI (I: 2 ≤ 4, II: >4). Serum t-CAF was significantly higher in the obese group compared to the controls, as were urinary α-GST, netrin-1, π-GST, and calprotectin. No difference was found between the two obese groups. In normoalbuminuric obese children and adolescents without significant metabolic disorders, serum t-CAF may be a new biomarker for the early detection of renal dysfunction, and urinary netrin-1, α-GST, π-GST, and calprotectin may be better indicators for the detection of early tubular damage, independent of the severity of obesity.

Background and aims: Due to the severe acute respiratory syndrome coronavirus 2 pandemic, governments of many countries decided to implement lockdowns, which included school closures. This major lifestyle change also applied to people with diabetes. The aim of this paper was to analyze how the COVID-19 pandemic and related restrictions influenced the metabolic compensation of diabetes in the pediatric population.Methods: Patients with type 1 diabetes (T1D), treated by one therapeutic team, who in 2020 and 2021 paid at least two in-person visits in the outpatient clinic, were included in the study. The time in range (TIR) and HbA1c, as well as the total daily dose (TDD) of insulin and BMI from the visit before the announcement of the pandemic restrictions (March 2020) and during the lockdown (second visit after 6 months) and within the period of loosened restrictions (two visits in 2021) were analyzed.Results: A total of 185 patients with T1D were included in the study (96 boys), aged 2–18 years (11.5 ± 3.5); 135 of them (72.9%) use CSII and 142 (76.8%) use CGM or FGM. During the first months of the studied period, despite comparable (p>0.05) TIR (57.5 ± 21.4% vs. 59.9 ± 20.5%), improvement of HbA1c was noticed (7.9 ± 1.6% vs. 7.5 ± 1.4%, p=0.0336), whereas in the following months, both HbA1c and TIR were comparable. Also, the TDD increased significantly (from 37.3 ± 18.9 units/day on the first visit up to 46.8 ± 22.7 units/day on the last visit, p=0.0003); however, TDD/kg remained constant (p>0.05) (0.8 ± 0.2 units/kg/day vs. 0.8 ± 0.3 units/kg/day) possibly due to an increased BMI (19.1 ± 3.7 kg/m²vs. 20.9 ± 4.1 kg/m², p=0.0001). The percentage of basal insulin in the TDD remained stable (p>0.05) (39.7 ± 11.3% vs. 39.3 ± 13.6%). Furthermore, a significant (p=0.0001) change in the BMI percentile was noticed [from 58.9 ± 26.2 percentiles (%iles) before lockdown vs. 64.6 ± 26.0%iles on the second visit]. However, the BMI percentile returned to baseline (58.1 ± 28.4%iles) at the visit at the end of the observation period.Conclusions: The parameters of metabolic control in pediatric patients with T1D during the pandemic period remained stable; however, weight gain and an increase in daily insulin dose have been observed, possibly due to reduced physical activity.

There are several observations that the onset of coronavirus 19 (COVID‐19) pandemic was associated with an increase in the incidence of diabetic ketoacidosis (DKA). However, due to heterogeneity in study designs and country‐specific healthcare policies, more national‐level evidence is needed to provide generalizable conclusions. To compare the rate of DKA in Polish children diagnosed with type 1 diabetes (T1D) between the first year of COVID‐19 pandemic (15 March 2020 to 15 March 2021) and the preceding year (15 March 2019 to 15 March 2020). Reference centers in 13 regions (covering ~88% of Polish children) retrospectively reported all new‐onset T1D cases in children from assessed periods, including DKA status at admission, administered procedures and outcomes. Secondly, we collected regions' demographic characteristics and the daily‐reported number of COVID‐19‐related deaths in each region. We recorded 3062 cases of new‐onset T1D (53.3% boys, mean age 9.5 ± 4.3 years old) of which 1347 (44%) had DKA. Comparing pre‐ and post‐COVID‐19 period, we observed a significant increase in the rate of DKA (37.5%–49.4%, p < .0001). The fraction of moderate (+5.4%) and severe (+3.4%) DKA cases increased significantly (p = .0089), and more episodes required assisted ventilation (+2.1%, p = .0337). Two episodes of DKA during 2020/2021 period were fatal. By region, change in DKA frequency correlated with initial COVID‐19 death toll (March/April 2020) (R = .6, p = .0287) and change in T1D incidence (R = .7, p = .0080). The clinical picture of new‐onset children T1D in Poland deteriorated over a 2‐year period. The observed increase in the frequency of DKA and its severity were significantly associated with the overlapping timing of the COVID‐19 epidemic.

Diabetic kidney disease belongs to the major complications of diabetes mellitus. Here, hyperglycaemia is a key metabolic factor that causes endothelial dysfunction and vascular changes within the renal glomerulus. The aim of the present study was to assess the function of the vascular endothelium in children with type 1 diabetes mellitus (type 1 diabetes) by measuring selected endothelial lesion markers in blood serum. The selected markers of endothelial lesions (sVCAM-1, sICAM-1, sE-SELECTIN, PAI-1, ADMA and RAGE) were assayed by the immunoenzymatic ELISA method. The study involved 66 patients (age: 5–18 years) with type 1 diabetes and 21 healthy controls (age: 5–16 years). In the type 1 diabetes patients, significantly higher concentrations of all of the assayed markers were observed compared to the healthy controls (p < 0.001). All of the evaluated markers positively correlated with the disease duration, the age, and BMI of the patients, while only PAI-1 and sE-SELECTIN were characteristic of linear correlations with the estimated glomerular filtration rate (eGFR). It can be concluded that endothelial inflammatory disease occurs in the early stages of type 1 diabetes mellitus in children. The correlations between PAI-1, sE-SELECTIN, and eGFR suggest an advantage of these markers over other markers of endothelial dysfunction as prognostic factors for kidney dysfunction in children with type 1 diabetes.

Klotho concentration may be considered as a prognostic factor in the development of chronic complications of diabetes. Moreover, decrease in sKlotho concentration may contribute to beta cell apoptosis and type 1 diabetes development. The aim of this study was to evaluate if sKlotho protein concentration in children with type 1 diabetes (T1D) and its correlation with classical risk factors of chronic complications of diabetes: dysglycemia and endothelial dysfunction.Material and methods: In a cross-section single center study the levels of soluble Klotho protein in 80 T1D (37 boys) and 34 healthy children (controls, 15 boys). Micro- and macroangiopathy were excluded and renal function was normal in all participants. Serum sKlotho, sICAM-1, sVCAM-1 and E-selectin levels were measured.Results: The concentration of sKlotho was lower in T1D than in the controls (2041.9 ± 1017.6 pg/mL vs. 2790.3 ± 1423.9 pg/mL, p=0.0113). sICAM-1, sVCAM-1 and E-selectin concentrations were comparable in patients and controls. In T1D, sKlotho was not correlated with the duration of diabetes. Klotho and E-selectin were correlated with HbA1c (r=-0.31, P=0.0066 and r=0.25, P=0.0351, respectively), but not with AVBG and blood glucose SD. Correlations of sKlotho with total cholesterol (r=0.31, P=0.0129), HDL-cholesterol (r=0.43, P=0.0011) and LDL-cholesterol (r=0.28, P=0.0412), but not with triglycerides, were found. Likewise, Klotho was not correlated with sICAM-1, sVCAM-1, and E-selectin concentrations.Conclusions: This study reports the significantly lower level of s-Klotho in children with type 1 diabetes, correlated with HbA1c and HDL cholesterol, but not with the adhesion molecules concentrations nor the duration of the disease. Negative correlation between the levels of HbA1c and soluble Klotho may suggest its possible involvement in the development of chronic diabetes complications.