Band 33, Heft 2

Background Insulin pumps are a frequently used technology among youth with type 1 diabetes. Air bubbles within insulin pump tubing are common, preventing insulin delivery and increasing the risk of large glycemic excursions and diabetic ketoacidosis (DKA). We sought to determine the prevalence of air bubbles in insulin pump tubing and identify factors associated with clinically significant air bubbles. Methods Fifty-three subjects were recruited over 65 office visits. The insulin pump tubing was visualized, and any air bubbles were measured by length. The length of air bubbles was then converted to time without insulin at the lowest basal rate. Generalized linear model (GLM) was used to determine the associations between air bubble size and other variables. Results Of the 65 encounters, 45 had air bubbles in the tubing. Five (5/65 = 7.7%) encounters had a time without insulin of more than 60 min. Air bubble size was inversely correlated with time since infusion set change (p < 0.001), and directly correlated with age of the subject (p = 0.049). Conclusions Significantly more air bubbles were found in the tubing of insulin pumps soon after infusion set change and with older subjects, suggesting a relationship with the technique of filling the insulin cartridge and priming the tubing.

Background Various gastrointestinal (GI) symptoms are associated with diabetes. Common GI complaints associated with the manifestation of the disease include abdominal pain, diarrhea, nausea, bloating and vomiting. There have been very few studies examining GI problems of pediatric patients with type 1 diabetes mellitus (T1DM). The aims of this study were to find out the prevalence of GI symptoms in pediatric patients with T1DM and to determine the correlation among such symptoms, duration of diabetes and glycemic control. Methods One hundred and thirty-seven (median age 13.2 years, female 45.3%) patients with T1DM were examined. Demographic features, GI symptoms, signs and physical examination findings of the patients were recorded by pediatric gastroenterology specialists for the differential diagnosis and exclusion of other etiologies. Complete blood count, blood glucose, lipid profile, electrolytes, amylase, lipase, celiac antibodies and glycated hemoglobin (HbA 1c ) levels were evaluated and stool examination was performed. Endoscopy was performed on the patients who had refractory GI complaints. Gastric emptying (GE) time was evaluated using GE scintigraphy. Results Overall, 74 (54%) patients had ≥1 GI complaints. Patients often reported gastroesophageal reflux (32.8%) and abdominal pain (18%). The most significant findings in terms of GI symptoms were determined when patients were classified according to the glycemic control status. Reflux and dyspeptic symptoms were significantly more common in poorly or very poorly controlled diabetic patients (p=0.003 and p=0.004, respectively). Conclusions Diabetes can affect the entire GI tract, and GI symptoms are common in pediatric patients. We recommend that T1DM patients be evaluated for GI symptoms.

Background Non-adherence to diabetes medication leads to poor outcomes and increased healthcare costs. Multiple factors affecting adherence in adults with type 2 diabetes (T2D) have been identified, but pediatric data is sparse. We aimed to determine whether initiation of additional oral medications or insulin affects adherence to primary study medication (PSM) in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. Methods Six hundred and ninety-nine youth (aged 10–17 years) with recent-onset T2D were randomized in the TODAY study. Participants were categorized as adherent (≥80% taken by pill count) or non-adherent (<80%), and adherence was compared between those on additional medications or not. Subgroup analyses to assess influence of race/ethnicity, gender, medication type, or depression were performed. Results At 36 months, 46.3% of participants were taking additional oral medications and 31.9% were on insulin. There was no difference in study medication adherence with additional oral medications (55.1%, 67.1%, and 56.7% at month 36 in those prescribed 0, 1, or 2+  additional medications; p = 0.16). Girls on oral contraceptives (OC) had higher adherence (65.2% vs. 55.8% at month 36; p = 0.0054). Participants on insulin had lower adherence (39.7% vs. 59.3% at 36 months; p < 0.0001). There was decreased adherence in participants with baseline depression (p = 0.008). Conclusions Additional oral medications did not influence adherence to diabetes medications in TODAY. Addition of insulin led to reduced adherence. In subgroup analyses, OC use was associated with higher adherence in girls, while baseline depression was associated with lower adherence overall. Further studies examining potentially modifiable risk factors of adherence in pediatric T2D are needed.

Background Ghrelin and obestatin are two gastric hormones encoded by the same preproghrelin gene that convey information concerning nutritional status to the central nervous system. Ghrelin has been considered as an appetite stimulating peptide that has a role in the regulation of energy homeostasis. Obestatin has been described for its appetite suppressing effects opposing ghrelin’s effect on food intake. The study aimed to evaluate ghrelin, obestatin and the ghrelin/obestatin ratio in obese children compared to non-obese and correlate them to food macronutrients intake. Methods This study is a cross-sectional case control study comprising 60 obese children, in addition to 31 age- and sex-matched controls. All children were subjected to clinical examination, anthropometric assessment, and a 3-day 24-h dietary recall. Fasting serum ghrelin and obestatin levels were evaluated, the ghrelin/obestatin ratio was calculated and they were correlated to macronutrients intake. Results Obese children had significantly lower serum fasting levels of ghrelin, obestatin and the ghrelin/obestatin ratio than the control group. The mean intake of total energy and macronutrients was significantly higher in obese children. Ghrelin showed positive correlation with total energy and fat intake in the obese group. Obestatin had positive correlations with total energy and fat intake while the ghrelin/obestatin ratio had a negative correlation with the total energy intake in the control group. Conclusions Ghrelin, obestatin and the ghrelin/obestatin ratio were significantly lower in obese children and significantly associated with their total energy intake. Disturbed ghrelin to obestatin balance may have a role in the etiology and pathophysiology of obesity.

Background Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disorder in the pediatric population and has grown along with the obesity pandemic in which we live today. Adipose tissue storage in the upper body segment has been positively correlated with visceral adiposity and metabolic disease, which suggests that neck circumference could represent an easily accessible and replicable anthropometric measurement to identify patients with a higher risk of developing NAFLD. The main purpose of this study is to determine if there is an association between neck circumference and NAFLD. The secondary objectives are to establish cutoff values based on gender and puberty staging. Methods We included a sample pediatric population of 112 patients diagnosed with obesity aged between 6 and 18 years. We performed anthropometric and metabolic measurements on every patient, and NAFLD diagnosis was determined with hepatic ultrasound. Results The neck circumference was larger in NAFLD pediatric patients compared to those without NAFLD (p = 0.001). In a multivariate analysis, the neck circumference was associated with NAFLD as an independent risk factor (odds ratio [OR] = 1.172; 95% CI = 1.008–1.362; p = 0.038). Tanner 2–3 = 35 cm and Tanner 4–5 = 38 cm were established as risk cutoff values to develop NAFLD in the male adolescent population. Conclusions There is an association between the neck circumference and NAFLD in pediatric patients with obesity, particularly in the male population.

Background There is no consensus on the definition of metabolically healthy obesity (MHO) and the diagnostic criteria in children. Objectives To estimate the prevalence of MHO and compare clinical and biochemical characteristics between MHO and metabolically unhealthy obesity (MUO), and to evaluate the association between MUO and cardiovascular disease (CVD) risk, anthropometrics and family background using different definitions in children. Methods This was a cross-sectional study. Participants included 224 obese children between the years 2007 and 2017. MHO was defined by three different criteria: (i) absence of metabolic syndrome (MHO-MS), (ii) no insulin resistance (IR) by homeostatic model assessment (HOMA) <3.16 cut-off (MHO-IR3.16) and (iii) absence of IR at <95th percentile for Mexican children (MHO-95th). Results The prevalence of MHO-MS, MHO-IR3.16 and MHO-IR95th was 12.9%, 56.3% and 41.5%, respectively. The prevalence of simultaneous MHO-MS plus MHO-IR95th was 5.36%. Children with MHO-MS vs. MUO-MS showed lower height, weight and body mass index (BMI) percentiles; MHO-IR3.16 vs. MUO-IR3.16 showed lower age, acanthosis, Tanner, waist circumference (WC), waist-to-height ratio (WHtR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and glucose; and MHO-IR95th vs. MUO-IR95th showed lower acanthosis, WC, DBP, glucose and high high-density lipoprotein cholesterol (HDL-C). MUO-MS was associated with WC > 90th, type 2 diabetes mellitus (T2DM) in first-degree relatives and obesity in siblings. MUO-IR3.16 was associated with pubertal stages, WC > 90th, WHtR > 0.55 and fasting hyperglycemia. MUO-IR95th was associated with WHtR > 0.55 and HDL < 10th. MHO-MS and MHO-IR3.16 or MHO-IR95th did not have agreement. Conclusions The prevalence of MHO varied depending on the definition, although the real MHO with no MS or IR is very low. Low DBP and high HDL-C in MHO were present in any definition. Association of MUO with anthropometric, biochemical and family background differs across definitions.

Background Chronic inflammation plays a critical role in the development of obesity-related metabolic dysfunction. The tri-ponderal mass index (TMI) may be more effective than body mass index (BMI) for estimating body fat levels. This study compared the efficacy of BMI and TMI in screening for dyslipidemia, insulin sensitivity, and inflammation in childhood obesity. Methods This study included 80 children who were classified as normal weight, overweight or obese using standardized BMI (BMI standard deviation score [SDS]) and TMI measurements. Fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), triglycerides, total cholesterol, liver function enzymes, leptin, serum free fatty acid (FFA), fetuin-A, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-6 levels were evaluated using both classification systems. Results LDL-C levels significantly differed within the groups by BMI, and serum FFA levels differed only according to the TMI. Serum MCP-1, TNF-α, IL-6, and fetuin-A levels showed no difference according to the TMI or BMI SDS. Fetuin-A levels did not differ between the insulin-resistant and non-resistant cases. Fetuin-A was the only inflammatory marker positively correlated with BMI. No inflammatory markers correlated with TMI. Fetuin-A, MCP-1, TNF-α, and IL-6 correlated with each other, but not with metabolic parameters. Conclusions BMI SDS and TMI were associated with metabolic disturbances in childhood obesity. Weight versus height n values may be related more to metabolic parameters than to inflammatory changes.

Background Metabolic syndrome (MetS) is not only a problem of adulthood but is already present in children and adolescents. The aim of this study was to estimate the prevalence of MetS in adolescents and to identify the associated factors. Methods This was a cross-sectional study with 354 overweight and obese school-aged adolescents (10–19 years). Sociodemographic, anthropometric, clinical, biochemical and lifestyle variables were collected. MetS was identified according to the criteria proposed by the International Diabetes Federation (IDF). Multivariate logistic regression models were used to examine the associations between risk variables and MetS. Results The prevalence of MetS was 9.6%. Among adolescents with MetS, all of them had low high-density lipoprotein cholesterol (HDL-c), while 76.5% had hyperglycemia and 38.2% had hypertriglyceridemia. Only 12.1% did not present any component of MetS, while 40% had at least two components. Multivariate analysis showed that being a girl was a protective factor (odds ratio [OR] = 0.29, confidence interval [CI] = 0.13–0.65) for the presence of MetS, while obesity (OR = 3.63, CI = 1.62–8.17) and being insufficiently active (OR = 4.60, CI = 1.01–20.96) were the risk factors for MetS. Conclusions Obese and insufficiently active male adolescents are more likely to have MetS. Early identification of MetS components, especially among obese adolescents, is an important tool for the prevention of cardiovascular complications in adult life.

Background The salivary circadian diurnal cortisol plays an important role in growth and development. Inappropriate levels may induce changes associated with an increased risk of obesity later in life. It is unknown if there are differences in cortisol secretion pattern between overweight/obese infants when compared with theirs peers in infancy. Thus, this study aimed to compare the salivary cortisol secretion pattern in overweight/obese and normal-weight infants. Methods Thirty-three (overweight/obese = 17 and normal weight = 16) infants between 6 and 24 months of age had saliva samples collected upon awakening (T1), 30 min after waking (T2), at 12:00 am or before the baby’s meal (T3), and prior to bedtime (T4). Highly sensitive enzyme immunoassays were used for cortisol analyses. Results Salivary cortisol levels were similar between the groups: T1 (p = 0.22; 95% confidence interval [CI]: −5.65, 1.37), T2 (p = 0.24; 95% CI: −8.23, 2.17), T3 (p = 0.95; 95% CI: −3.16, 2.96), and T4 (p = 0.81; 95% CI: −1.39, 1.08); and no differences were observed between area under the curve (AUC) (p = 0.80; 95% CI: −4.58–13.66). The cortisol level reduced in T4 (95% CI: 1.35–2.96) compared to T1 (95% CI: 5.15–8.49) and T2 in the overweight/obese group (p < 0.001; 95% CI: 6.02–11.04). In the normal-weight group, the cortisol reduced in T3 (95% CI: 2.86–8.18) compared to T1 (95% CI: 5.64–12.28) and decreased until T4 (p = 0.001; 95% CI: 1.25–3.37). Conclusions The overweight/obese infant group presented a different pattern of cortisol secretion, although cortisol levels did not differ between the control group.

Background The prevalence of childhood obesity and its related comorbidities in Malaysia are alarming. Malaysia ranked second in childhood obesity among South-east Asian countries with a prevalence of 12.7%. This study was conducted to investigate the prevalence of non-alcoholic fatty liver disease (NAFLD) among obese children and to ascertain the predictors associated with NAFLD. Methods NAFLD was diagnosed via ultrasonographic evidence of fatty liver in obese and overweight children who presented to the Paediatric Obesity Clinic of University Malaya Medical Centre (UMMC), Malaysia. Demographic, anthropometric, clinical and biochemical parameters were analysed and compared between the NAFLD and non-NAFLD groups. Statistical analyses were carried out. Results Twenty-one out of 33 obese and overweight children (63.6%) were found to have NAFLD. We found that 62% of our study population in the NAFLD group had metabolic syndrome based on the definition by the International Diabetes Federation (IDF). Mean body mass index (BMI), waist circumference (WC), triglyceride (TG) and alanine aminotransferase (ALT) were found to be significantly greater in the NAFLD group compared to the non-NAFLD group (35.2 [6.1] vs. 29.3 [4.7] kg/m 2 [p-value 0.007]; 104.1 [11.4] vs. 94.1 [12] cm [p-value 0.034]; 1.5 [0.9] vs. 0.9 [0.3] mmol/L [p-value 0.002]; 60.7 [53.8] vs. 27.3 [13] U/L [p-value 0.007]). Multivariate regression analysis revealed TG as the independent predictor for NAFLD, with an odds ratio of 41.7 (95% confidence interval [CI] 0.001, 0.819) (p-value 0.04). Conclusions Prevalence of NAFLD among children who are obese and overweight is alarming with 62% having metabolic syndrome. TG was found to be a strong predictor for NAFLD.

Background Severe early-onset obesity (SEOO) in children is a common feature of monogenic obesity. Gene defects of the leptin-melanocortin pathway can be analysed biochemically and genetically. The aim of this study was to search for children with leptin deficiency or biologically inactive leptin in a cohort of children with SEOO and to study associations between leptin parameters and anthropometric data. Methods The cohort included n = 50 children with SEOO (22 boys) who were recruited at one of four study centres (Germany: Ulm; Poland: Katowice, Szczecin, Rzeszow) between October 2015 and October 2017. Weight (kg) and height (m) were measured, Tanner stage was obtained and a fasting serum blood sample was taken. Serum levels of total leptin (LEP, ng/mL), biologically active leptin (bioLEP, ng/mL) and soluble leptin receptor (sLEPR, ng/mL) were measured. The body mass index (BMI [kg/m 2 ]), BMI z-score (World Health Organization [WHO]), quotient of bioLEP/LEP and leptin-standard deviation score (LEP-SDS) (Tanner stage, BMI and sex-adjusted) were calculated. Results We did not find any child with leptin deficiency or biologically inactive leptin in our cohort. The serum LEP and bioLEP levels were strongly correlated with age (r = 0.50, p < 0.05) and BMI (r = 0.70; p < 0.0001). Girls had higher LEP and bioLEP levels (49.7 ± 35.9 vs. 37.1 ± 25.5 ng/mL, p > 0.05) as well as lower LEP-SDS than boys (−1.77 ± 2.61 vs. −1.40 ± 2.60, p > 0.05). sLEPR levels were negatively correlated with BMI values (r = −0.44; p < 0.05), LEP (r = −0.39; p < 0.05) and bioLEP levels (r = −0.37; p < 0.05). Interestingly, there was a strong inverse relationship between LEP-SDS and BMI (r = −0.72, p < 0.001). Conclusions In this cohort with SEOO, we identified no new cases of children with leptin deficiency or bioinactive leptin. A strong negative correlation between the LEP-SDS and BMI values could be interpreted as relative leptin deficiency in children with SEOO. In case this hypothesis can be confirmed, these children would benefit from a substitution therapy with methionyl human leptin (metreleptin™).

Background The relationship between cytokines and lipid metabolism has garnered attention given their potential metabolic interaction. However, the relationship between adropin and lipopolysaccharide-binding protein (LBP) and obesity-related inflammation has not been reported, as well as their relationship with serum lipid profiles. Objective This study analyzed the association of serum adropin, leptin, LBP levels and lipid profiles in obese children ranging from 5 to 14 years old. Methods Plasma lipid measurements included total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) by standard methods, and serum adropin, leptin and LBP levels was measured by enzyme-linked immunosorbent assay (ELISA). Results One hundred and twenty-four children (9.25 ± 1.59 years) with obesity and 42 controls (8.81 ± 1.94 years) were assessed. Compared with the control group, the serum adropin concentrations in the obesity group were significantly lower, whereas the serum leptin and LBP levels were significantly higher. Pearson’s correlation analysis showed that serum adropin levels negatively correlated with TG, waist to hip ratio (WHR) and body mass index (BMI), and positively correlated with HDL-c. Serum LBP levels positively correlated with LDL-c and WHR. After adjusting for LBP, the correlation coefficients of adropin with TG, HDL-c and leptin were more robust. Also, after adjusting for serum LBP, the correlation coefficient of leptin with TG was attenuated, yet remained statistically significant, and the correlation coefficient of leptin with HDL-c was enhanced. Conclusions Children with obesity have decreased serum adropin levels and elevated leptin and LBP levels. Each of the three serum cytokines were associated with lipid metabolism, and this association warrants further study.

Background The olfactory bulb (OB) and eyeball size change depending on age and puberty. There is a well-established trade-off between sensory structures of the brain such as the eye and the olfactory bulb that depend on environmental circumstances in the evolutionary history of animals. The aim of this study was to developmentally investigate the potential reciprocal changes between OB and eyeball volumes (EV) in girls with precocious puberty (PP). Methods A total of 148 girls aged between 5 and 8 years (63 PP, 85 healthy) were included in the study. Exclusion criteria: Cases of anosmia/hyposmia, neurodegenerative disorder, refractive errors and trauma. The pituitary height (PH), EV and OB volumes were measured on segmentation of a magnetic resonance image (MRI) slice using manual countering. The corrected measurements by body surface were used in all statistical analyses. Results In girls with PP, the means of the OB volume and PH were larger (71.11 ± 20.64 mL) and higher (4.62 ± 1.18 mm), respectively, while the mean of EVs was smaller (11.24 ± 2.62 cm 3 ) (p = 0.000). Cut-off values were 62.27 mL, 10.7 cm 3 and 4.71 mm for OB volume, EV and PH, respectively. While negative correlations were found between OB volume-EV and EV-PH (r 63  = −0.224, p = 0.001 and r 63  = −0.116, p = 0.001, respectively), OB volume was positively correlated with PH (r 63  = 0.578, p = 0.001). Conclusions The present study demonstrates that girls with PP have significantly larger OB volume, but smaller EV, and there is negative correlation between the two structures. These results indicate that there is trade-off between anatomical dimensions of OB and eyeball in favor of OB in PP girls.

Background We depicted gender-differences in metabolic syndrome (MS) clustering before and after puberty in pediatrics, in order to develop gender specific preventive strategies for childhood obesity. Methods We considered 1079 children and adolescents (529 females and 550 males; mean age 11.5 ± 2.8 year). According to body mass index (BMI) percentiles the subjects were classified as normal weight BMI <75th, overweight BMI 75–95th and with obesity BMI >95th. MS was diagnosed when three of the following criteria for age and sex percentiles were met: BMI >95th, triglycerides (TGs) level >95th, high-density lipoprotein-cholesterol (HDL-c) level <5th, blood pressure (blood pressure) >95th percentile, fasting blood glucose (FBG) >100 mg/dL and/or homeostatic model assessment- insulin resistance (HOMA-IR) >97.5th percentile. Results The prevalence of dismetabolic factors was similar in both genders, except for pathological BP, which was higher in males (p = 0.02). MS was detected only in patients with obesity, with a higher prevalence in pubertal than late/post-pubertal subjects (p < 0.001), without any significant difference between gender. In pre-puberty, the most common MS combination was obesity (HBMI) + hypertension (HBP) + hyperglycemia/insulin resistance (HGLY/IR) followed by HBMI + low HDL-levels (LHDL) + HGLY/IR versus HBMI + HBP + HGLY/IR followed by HBMI + HBP + LHDL, respectively, in females and males. In the early and late/post-pubertal periods, the most prevalent combination remained similar to pre-puberty, additionally in both sexes other combinations, such as HBMI + HTG + HBP + HGLY/IR, HBMI +  HBP + LHDL + HGLY/IR, HBMI + HTG + LHDL + HGLY/IR and HBMI + HTG + LHDL + HBP + HGLY/IR were also detected, differently distributed in males and females. Conclusions We confirm that MS is an important consequence related to obesity, particularly in the post-puberty stage. Some gender-based differences should be considered early in order to identify specific preventive and treatment strategies.

Background Alkaptonuria (OMIM: 203500) is an inborn error of metabolism due to homogentisate 1,2-dioxygenase homogentisic acid 1,2 dioxygenase (HGD) enzyme deficiency. Due to the enzyme deficiency, homogentisic acid cannot be converted to maleylacetoacetate and it accumulates in body fluids. Increased homogentisic acid is converted to benzoquinones, the resulting benzoquinones are converted to melanin-like pigments, and these pigments are deposited in collagen – this process is called ochronosis. In patients with alkaptonuria, the urine is darkened, which is misinterpreted as hematuria, the incidences of renal stones, arthritis and cardiac valve calcification are increased, and spontaneous tendon ruptures, prostatitis and prostate stones can be encountered. The present study aimed to evaluate the HGD gene mutations in 14 patients with alkaptonuria. Methods Fourteen patients diagnosed with alkaptonuria and followed up from 1990 to 2014 were retrospectively evaluated. Their demographic, clinical and treatment-related data were retrieved from hospital files. For mutation analysis, genomic DNAs of the patients were isolated from their peripheral blood samples. Variations in the HGD gene were scanned on the HGD-mutation database (http://hgddatabase.cvtisr.sk). Results Among 14 patients, the female/male ratio was 1/1 and the median age was 9 years (range, 6–59 years). All patients were symptomatic at their first visit and the most common symptom was dark urine (71%) followed by arthralgia. Independent of the urinary homogentisic acid concentrations, patients with the presenting symptom of arthralgia were elder. Nine different mutations including p.Ser59AlafsX52, p.Gly161Arg, p.Asn219Ser, p.Gly251Asp, p.Pro274Leu, p.Arg330Ser, p.Gly372Ala, c.656_657insAATCAA and a novel mutation of p.Val316Ile were detected. All of the pediatric-age patients (n = 13) were treated with ascorbic acid at a dose of 250–1000 mg/day. Conclusions Nine different HGD gene mutations with a novel one, p.Val316Ile, were detected. The most common mutation was p.Ser59AlafsX52 for the HGD gene followed by p.Gly161Arg and p.asn219Ser, which can be considered specific to the Turkish population.

Background Congenital adrenal hyperplasia (CAH) is a chronic disorder causing adrenal insufficiency and hyperandrogenism affecting the quality of life (QOL). The objective of the study was to assess the health-related QOL (HRQOL) in Egyptian children and adolescents with CAH and to identify factors affecting it. Methods This cross-sectional study included 200 CAH patients (with 21-hydroxylase deficiency [21-OHD]) who were assessed according to their age, sex, clinical phenotype, timing of genitoplasty, hospital admissions within the last year, compliance to treatment, regularity of follow-up, presence of complications and hormonal control. HRQOL was assessed using the World Health Organization (WHO)QOL-BREF questionnaire with four domains analyzed independently including physical, psychological, social and environmental domains, with higher scores indicating better QOL. Results The study included 140 females and 60 males with a mean age of 6.6 ± 4.5 years, and 88% were salt-wasting (SW). Older patients had significantly lower QOL scores (r = − 0.151, p = 0.033). The physical domain correlated significantly with the degree of virilization (r = − 0.491, p = 0.001) and frequency of hospitalization (r = − 0.495, p < 0.001). The psychological domain was affected by age (r = − 0.157, p = 0.026) and timing of genitoplasty (r = − 0.326, p = 0.001), while the social domain was affected by age (r = −0.277, p < 0.005) and pubertal stage (r = − 0.195, p = 0.006). Females had lower scores at the psychological domain (p < 0.001), whereas males had lower scores at the physical domain (p = 0.003). Salt-losing patients had lower scores at the physical domain (p = 0.001). Patients with good hormonal control had higher scores at the physical domain (p = 0.03). Genitoplasty affected both psychological and social domains (p = 0.003 and 0.01, respectively). Patients with hypertension and hirsutism had lower QOL scores (p < 0.05). Conclusions HRQOL was relatively more affected in CAH patients with older age, poor hormonal control, high frequency of hospital admissions and those who developed complications.

Background Familial hypophosphatemic rickets, which is usually acknowledged as X-linked hypophosphatemic rickets (XLH), is a rare hereditary disease. XLH caused by mutations in the PHEX gene often manifests as growth retardation, skeletal deformities, osteodynia and dental dysplasia. NPR2 mutations are reported to cause disproportionate short stature. Our study was designed to identify the gene mutations of three patients in one family. Case description A 40-year-old Chinese male visited the hospital for continuous osteodynia and presented with bilateral leg bowing, absent teeth and a progressive limp. The age of onset was approximately 2 years old. His 63-year-old mother and 42-year-old brother both shared identical symptoms with him. The laboratory tests were consistent with XLH, which showed decreased levels of blood phosphorus and 1,25-dihydroxyvitamin D 3 as well as increased urinary phosphorus excretion. Mutation analysis revealed that the proband as well as his mother and his brother all had a PHEX mutation in exon 14 (c.1543C > T), and the proband also had a NPR2 mutation in exon 21 (c.3058C > T). Conclusions We report the familial hypophosphatemic rickets of three patients in a Chinese family caused by a PHEX gene mutation in exon 14 (c.1543C > T), which had never been reported in Chinese patients. We first report an XLH case together with a NPR2 mutation that had never been reported before.

Background Hereditary vitamin D resistant rickets (HVDRR) is a bone disorder characterized by a phenotype of rickets with onset at early stage of life with elevated alkaline phosphatase, hypocalcemia, hypophosphatemia, hyperparathyroidism and elevated levels of 1,25-dihydroxyvitamin D (calcitriol) as a consequence of the resistance of the vitamin D receptor (VDR). Mutations in the DNA-binding domain of the VDR of the vitamin D receptor have been characterized by a lack of response to traditional treatment with calcium and calcitriol. Secondary hyperparathyroidism and hypophosphatemia are the main factors in its pathogenesis. Cinacalcet is a calciomimetic drug that reproduces the action of calcium by increasing the sensitivity of the calcium-sensitive receptors (CASR) of the parathyroid glands that regulate the secretion of the parathyroid hormone (PTH). Case presentation We describe its effectiveness and safety in a patient with HVDRR and review other published report cases in the literature. According to published experience, cinacalcet could be used as an adjunctive treatment for the HVDRR with mutations in the DNA-binding domain of the VDR refractory to traditional treatment. Due to lack of knowledge of possible effects of cinacalcet on CASR in the skeleton, long-term use should be avoided. Conclusions The optimal dose of cinacalcet for treatment of HVDRR ranges between 0.25 and 0.5 mg/kg/day. Serious side effects of cinacalcet have not been published in this type of patient, although we considered that a close monitoring is necessary in order to detect hypocalcemia.

Background Cerebral edema (CE) is one of the most serious complications of diabetic ketoacidosis (DKA) and can result in central nervous system (CNS) disorders and even lead to death of the patient. Case presentation We present the case of a 11-year-old boy with severe DKA in the course of newly diagnosed type 1 diabetes (T1D). The delay in the diagnosis of DKA and some therapeutic problems contributed to the development of CE and direct life-threatening conditions. Early diagnosis of CE development in the course of DKA using non-invasive methods such as pachymetry or transorbital ultrasound seems to be a very important prognostic factor. Conclusions This case highlights the importance of appropriate treatment according to the newest recommendations and presents the usefulness of new diagnostic methods to assess the risk of CE in children with newly diagnosed T1D.