Rickets is a metabolic bone disease that develops as a result of inadequate mineralization of growing bone due to disruption of calcium, phosphorus and/or vitamin D metabolism. Nutritional rickets remains a significant child health problem in developing countries. In addition, several rare genetic causes of rickets have also been described, which can be divided into two groups. The first group consists of genetic disorders of vitamin D biosynthesis and action, such as vitamin D-dependent rickets type 1A (VDDR1A), vitamin D-dependent rickets type 1B (VDDR1B), vitamin D-dependent rickets type 2A (VDDR2A), and vitamin D-dependent rickets type 2B (VDDR2B). The second group involves genetic disorders of excessive renal phosphate loss (hereditary hypophosphatemic rickets) due to impairment in renal tubular phosphate reabsorption as a result of FGF23-related or FGF23-independent causes. In this review, we focus on clinical, laboratory and genetic characteristics of various types of hereditary rickets as well as differential diagnosis and treatment approaches.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-resident protein that plays a crucial role in attenuating ER stress responses. Although MANF is indispensable for the survival and function of mouse b-cells, its precise role in human b-cell development and function is unknown. In this study, we show that lack of MANF in humans results in diabetes due to increased ER stress, leading to impaired b-cell function. We identified two patients from different families with childhood diabetes and a neurodevelopmental disorder associated with homozygous loss-of-function mutations in the MANF gene. To study the role of MANF in human b-cell development and function, we knocked out the MANF gene in human embryonic stem cells and differentiated them into pancreatic endocrine cells. Loss of MANF induced mild ER stress and impaired insulin-processing capacity of b-cells in vitro. Upon implantation to immunocompromised mice, the MANF knockout grafts presented elevated ER stress and functional failure, particularly in recipients with diabetes. By describing a new form of monogenic neurodevelopmental diabetes syndrome caused by disturbed ER function, we highlight the importance of adequate ER stress regulation for proper human b-cell function and demonstrate the crucial role of MANF in this process.

Objectives Recent studies have demonstrated an increase in the frequency of idiopathic central precocious puberty (CPP) during the severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic. We compared the demographic, anthropometric, and clinical characteristics of idiopathic CPP patients diagnosed during a one-year period of the COVID-19 pandemic with the characteristics of patients diagnosed during the same period in the previous three-years. Methods Demographic, clinical, anthropometric, and laboratory data of all patients diagnosed in our Pediatric Endocrinology clinic with idiopathic CPP during a one-year period of the COVID-19 pandemic (April 2020–March 2021) and a three-year period before the pandemic (April 2017–March 2020) were evaluated retrospectively. Results A total of 124 patients (124 girls, zero boys) diagnosed with idiopathic CPP were included in this study. Sixty-six patients in the three-year period before the COVID-19 pandemic (April 2017–March 2020) and 58 patients (46.8%) in the one-year period during the COVID-19 pandemic period (April 2020–March 2021) were diagnosed with idiopathic CPP. Conclusions This study’s findings suggest that the number of girls diagnosed with idiopathic CPP during the one-year study period during the pandemic was more than double that of any of the previous three-years.

Objective:To investigate the relationship between zonulin levels and clinical and laboratory parameters of childhood obesity.Methods:The study included obese children with a body mass index (BMI) >95th percentile and healthy children who were of similar age and gender distribution. Clinical (BMI, waist circumferences, mid-arm circumference, triceps skinfold, percentage of body fat, systolic blood pressure, diastolic blood pressure) and biochemical (glucose, insulin, lipid levels, thyroid function tests, cortisol, zonulin and leptin levels) parameters were measured.Results:A total of 43 obese subjects (23 males, mean age: 11.1±3.1 years) and 37 healthy subjects (18 males, mean age: 11.5±3.5 years) were included in this study. Obese children had significantly higher insulin, homeostasis model assessment of insulin resistance, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), zonulin and leptin levels than healthy children (p<0.05), while glucose levels were not different (p>0.05). Comparison of the obese children with and without insulin resistance showed no statistically significant differences for zonulin levels (p>0.05). Zonulin levels were found to negatively correlate with HDL-C and positively correlate with leptin levels, after adjusting for age and BMI.Conclusion:To the best of our knowledge, this is the first study investigating the relationship between circulating zonulin level (as a marker of intestinal permeability) and insulin resistance and leptin (as markers of metabolic disturbances associated with obesity) in childhood obesity. The results showed that zonulin was significantly higher in obese children when compared to healthy children, a finding indicating a potential role of zonulin in the etiopathogenesis of obesity and related disturbances.

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