Exploring systemic inflammation in children with chronic kidney disease: correlates of interleukin 6.

BACKGROUND: Systemic inflammation (SI) is linked to chronic kidney disease (CKD) progression and multiple complications. Data regarding SI biomarkers in pediatric patients are scarce. This case-control and cross-sectional study investigates the correlation of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), total iron binding capacity (TIBC) and serum albumin to serum interleukin-6 (IL-6). METHODS: NLR and PLR were measured in 53 patients (median age: 12.9 years), including 17 on dialysis and 36 with a median glomerular filtration rate of 39 ml/min/1.73m2, and in 25 age and sex-matched healthy controls. Iron profile, serum albumin and IL-6 were measured in the patient group. IL-6 levels > 3rd quartile were classified as high. RESULTS: Patients presented higher NLR and PLR and particularly those on dialysis (p < 0.001 and p = 0.001). We observed a significant correlation between natural logarithm (ln) of IL-6 (lnIL-6) and NLR (rs = 0.344, p = 0.014), serum albumin (rs = -0.350, p = 0.011) and TIBC (rs = -0.345, p = 0.012) after adjustment for CKD stage, while the correlation between lnIL-6 and PLR was not significant (rs = 0.206, p = 0.151). Combination of NLR, serum albumin and TIBC predicted high IL-6 (13 patients) with an AUC of 0.771 (95% CI 0.608-0.943). Pairing of NLR ≥ 1.7 and TIBC ≤ 300 µg/dL exhibited the highest sensitivity (76.9%), while incorporating serum albumin ≤ 3.8 g/dL along with them achieved the highest specificity (95%) for detecting high IL-6 levels. CONCLUSION: Both NLR and PLR levels increase in CKD, especially in patients on chronic dialysis. NLR, rather than PLR, along with TIBC and serum albumin, are associated with IL-6 in pediatric CKD.

Association Between Adipokine Profile, Systemic Inflammation, Muscle and Protein Energy Wasting in Children With Chronic Kidney Disease.

OBJECTIVES: This cross-sectional study explores the association of adipokines and interleukin-6 (IL-6) with muscle and protein energy wasting (PEW) in children with chronic kidney disease (CKD). METHODS: We measured serum adiponectin, leptin, resistin and IL-6 in 53 patients with CKD stage 3-5. Lean tissue (LTI) and fat tissue index (FTI) were estimated by bioimpedance analysis spectroscopy. PEW was defined as muscle wasting [LTI adjusted to height age (LTI HA) z-score < -1.65 SD) and at least 2 of the following: reduced body mass [body mass index adjusted to height age (BMI HA) z-score < -1.65 SD), poor growth [height z-score < -1.88 SD], questionnaire-based decreased appetite, and serum albumin ≤3.8 g/dL. RESULTS: PEW, observed in 8 (15.1%) patients, was more prevalent in CKD stage 5 (P = .010). Among the adipokines, adiponectin, and resistin levels were significantly higher in CKD stage 5 (P < .001, P = .005). Adiponectin was correlated to LTI HA z-score (Rs = -0.417, P = .002), leptin to FTI z-score (Rs = 0.620, P < .001), while no correlation was observed between resistin and body composition parameters. Resistin was the only adipokine correlated to IL-6 (Rs = 0.513, P < .001). After adjustment for CKD stage and patient age, PEW was associated with adiponectin and IL-6 rise by 1 µg/mL and 10 pg/mL respectively (odds ratio (OR) 1.240, 95% confidence interval (CI) 1.040, 1.478 and OR 1.405, 95% CI 1.075-1.836) but not with leptin, while resistin association with PEW lost its significance. CONCLUSIONS: In pediatric CKD, adiponectin is associated with muscle wasting, leptin with adiposity and resistin with systemic inflammation. Adiponectin and cytokine IL-6 may serve as PEW biomarkers.

Sources of error in direct radionuclide cystography in children and the need for a standardized, manometric apparatus.

Direct radionuclide cystography (DRC) is a safe and reliable method for the detection and follow-up of vesico-ureteral reflux (VUR). Since the first DRC was performed, during the early 60s, the method has undergone many refinements. Themanometric approach, which was first introduced in 1984, provides a correlation between the bladder pressure and VUR visualization. In this study the sources of error that may alter the results of DRC are discussed and a novel, standardized low costmanometric apparatus is suggested.

Bilateral Gonadoblastoma in a 6-Year-old Girl With Frasier Syndrome: Need for Early Preventive Gonadectomy.

Frasier syndrome (FS) is a rare condition, caused by splice-site mutations of intron 9 in the Wilms' tumor suppressor gene 1 (WT1 gene). The WT1 protein is essential for urogenital development and patients with 46XY karyotype present with female (FS type 1) or male phenotype, gonadal dysgenesis, progressive glomerulopathy, and high risk of gonadoblastoma. We describe a female patient with an IVS9+4C>T donor splice-site mutation, who underwent a preventive gonadectomy at the age of 6 years due to imaging findings of dysplastic gonads. The biopsy revealed bilateral gonadoblastoma, emphasizing the need for early gonadectomy in 46XY FS patients.

Association between insulin growth factor-1, bone mineral density, and frailty phenotype in children with chronic kidney disease.

BACKGROUND: This cohort study investigates the association between insulin growth factor-1 (IGF-1), bone mineral density, and frailty phenotype in children with chronic kidney disease (CKD). METHODS: Forty-six patients (median age 14.5 years) were prospectively enrolled. Frailty phenotype was defined as the presence ≥ 3 of the following indicators: suboptimal growth/weight gain (body mass index height age < 5th percentile or height < 3rd percentile or loss of ≥ 10 percentiles/year in at least one parameter), low muscle mass (lean tissue mass height age < 5th percentile or loss of ≥ 10 percentiles/year), general fatigue reported by parent or child, and C-reactive protein > 3 mg/l. Lumbar bone mineral apparent density (LBMAD) was measured by dual-energy X-ray absorptiometry, body composition by bioimpedance spectroscopy, and IGF-1 by enzyme-labeled chemiluminescent immunometric assay. RESULTS: Frailty phenotype (seven patients) was more frequent in advanced CKD (estimated glomerular filtration rate < 30 ml/min/1.73m2) (p = 0.014). IGF-1 and LBMAD z-scores were lower in patients with suboptimal growth/weight gain (14 patients) (p = 0.013, p = 0.012), low muscle mass (nine patients) (p = 0.001, p = 0.009), and general fatigue (eight patients) (p < 0.001, p = 0.004). IFG-1 and LBMAD z-scores were associated with frailty phenotype (OR 0.109, 95% CI 0.015-0.798 and OR 0.277, 95% CI 0.085-0.903) after adjustment for CKD stage. IGF-1 z-score was associated with LBMAD < 5th percentile (six patients) (OR 0.020, 95% CI 0.001-0.450) after adjustment for CKD stage. The association between LBMAD and frailty phenotype lost significance after adjustment for IGF-1. CONCLUSION: Frailty phenotype is more frequent in advanced pediatric CKD. IGF-1 is negatively associated with frailty phenotype and interferes in the association between frailty and LBMAD.

Association between relative fat mass, uric acid, and insulin resistance in children with chronic kidney disease.

INTRODUCTION: This cross-sectional study investigates the association between insulin resistance (IR) and serum uric acid (sUA) and relative fat (RFM) and lean mass (RLM) profiles in children with chronic kidney disease (CKD). MATERIAL AND METHODS: RLM and RFM were assessed by bioimpedance spectroscopy in 41 children and adolescents. Normal weight obesity (NWO) was defined as normal height-age body mass index and RFM >85th percentile, according to age and sex. Homeostatic model assessment of insulin resistance (HOMA-IR) level >95th percentile, according to sex and pubertal stage, and sUA >7 mg/dl were used to define IR and hyperuricemia, respectively. RESULTS: High RFM (15 patients) and NWO (7 patients) were associated with higher HOMA-IR in total (p < 0.001) and normal-weight patients (p = 0.004), respectively. RFM was positively and RLM negatively correlated to HOMA-IR (rs = 0.500, p = 0.001 and rs = -0.539, p < 0.001, respectively) and sUA (rs = 0.370, p = 0.017 and rs = -0.325, p = 0.038, respectively), while sUA was positively correlated to HOMA-IR (rs = 0.337, p = 0.031). Hyperuricemia (16 patients) was positively associated with higher RFM and HOMA-IR (p = 0.001 and p = 0.010, respectively). The correlation between sUA and HOMA-IR lost significance after adjustment for RFM. In logistic regression analysis, a 5% increase in RFM was associated with IR (11 patients) independently of the age, sex, sUA, and CKD stage in both total (OR 2.174, 95% CI 1.115-4.225) and normal-weight (OR 3.504, 95% CI 1.110-11.123) patients. CONCLUSION: Children with high RFM, including those presenting NWO, are at risk for IR regardless of CKD stage. RFM is probably the mediator of the link between sUA and IR.

Lesch-Nyhan syndrome due to a splice-site mutation in a 14-month-old boy presenting as acute renal failure.

Lesch-Nyhan disease (LND) is a rare X-linked recessive inherited disorder caused by mutations in HPRT1 gene resulting in deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). LND is characterized by hyperuricemia and a spectrum of neurological and behavioral manifestations. We describe a rare case of a 14-month-old boy presenting with acute renal failure and hyperuricemia. The patient exhibited all features of LNS apart from self-injurious behavior. The enzymatic analysis demonstrated total inactivity of the HPRT, and the molecular analysis revealed a splice-site mutation in intron 3 leading to exon 4 exclusion. This splice-site mutation has been previously reported only twice.

Ambulatory hemodynamic patterns, obesity, and pulse wave velocity in children and adolescents.

BACKGROUND: In recent years, pulse wave velocity (PWV) has emerged as a surrogate marker of cardiovascular disease in children with cardiovascular risk factors. The aims of the present study were to identify determinants of PWV in children according to their weight status and to investigate the role of peripheral blood pressure and central hemodynamic parameters in the association between PWV and obesity. METHODS: We included in the study healthy children and adolescents randomly selected from a school-based blood pressure screening study. All participants underwent ambulatory blood pressure monitoring and 24-h pulse wave analysis. RESULTS: Overweight and obese children had higher 24-h PWV, 24-h peripheral and central systolic blood pressure (SBP), and cardiac output than normal weight ones. Children with both overweight and hypertension presented the highest 24-h PWV values (p < 0.001). Peripheral and central SBP, body mass index (BMI), and hemodynamic parameters, including stroke volume, cardiac output, total peripheral resistance, and cardiac index, were all associated with 24-h PWV. However, in stepwise regression analysis, 24-h peripheral and central SBP and cardiac index, but not BMI, were independent predictors of 24-h PWV. There were statistically significant differences in 24-h blood pressure and hemodynamic parameters among those on the lower and highest 24-h PWV quartile, but there were no significant differences in BMI among 24-h PWV quartile groups. CONCLUSIONS: Arterial stiffness is higher in overweight and obese children in the co-presence of hypertension. Peripheral and central SBP are the main determinants of 24-h PWV independent of weight status. Graphical abstract.

Long-term outcome of pediatric kidney transplantation: A single-center experience from Greece.

Pediatric kidney Tx has critically altered the outcome in ESRD pediatric patients. The aims of this study were to determine long-term graft and patient survival in a homogeneous ethnic population. We reviewed the medical charts of pediatric kidney Tx performed between 1990 and 2012 in Greece. Seventy-five kidney Txs were performed from LRD and 62 from DD. The 10- and 20-yr graft survival was higher in LRD Tx compared with DD Tx. Both patient and graft survival at 10 and 20 yr after Tx were similar in LRD Tx from grandparents compared with parents (92.9% vs. 93.4% 20-yr patient survival, 71.4% vs. 78.7% and 57.1% vs. 72.1%, 10- and 20-yr graft survival, respectively). However, there was a decreasing tendency in LRD Tx rates in period 2001-2012 compared with period 1990-2000 (47.1% vs. 62.7%). Risk factors for poor five-yr graft survival were DD Tx, and induction treatment with ALG compared with basiliximab, but their effect attenuated at 10 yr after Tx. In conclusion, Tx from LRD may offer efficient survival outcomes irrespective of donor age, suggesting that even older LRD could be an excellent option for the 1st kidney Tx in children and adolescents.

aHUS associated with C3 gene mutation: a case with numerous relapses and favorable 20-year outcome.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is frequently associated with gene mutations in complement-regulatory proteins and activators. Different complement C3 gene mutations have been associated with different outcomes in aHUS. CASE-DIAGNOSIS/TREATMENT: We report the case of a 21-year-old male with a C3 heterozygous gene mutation (p.Ile1157Thr) who developed aHUS at the age of 10 months and had six relapses, the last at the age of 14.5 years. Each relapse was characterized by an apparent predominance of hematological manifestations with milder renal involvement and was followed by complete recovery, with creatinine values and hematological parameters usually recovering after the 3rd to 6th day of hospitalization. The patient was treated with plasma infusion, apart from the initial and the last episode, when dialysis was needed. Twenty years after the onset, he retains normal renal function, with no proteinuria or hypertension. One similar case of highly recurrent aHUS carrying the same C3 mutation as our patient with recovery of renal function has been previously reported. CONCLUSIONS: We further support that aHUS associated with the p.Ile1157Thr C3 mutation may be highly recurrent, but with recovered renal function. The prevalent p.Ile1157Thr C3 gene mutation has variable disease manifestations and both severe and milder renal phenotypes have been found.

Comparison of cotrimoxazole vs. second-generation cephalosporins for prevention of urinary tract infections in children.

BACKGROUND: Antimicrobial prophylaxis is recommended for the prevention of urinary tract infections (UTI) in high-risk children. However, there is growing concern about the use of ß-lactams as prophylaxis and subsequent development of antibiotic resistance. METHODS: In this prospective, randomized, crossover controlled trial we compared cotrimoxazole (SXT) and second-generation cephalosporins (2GC) as UTI prophylaxis in children ranging in age from 1 to 60 months. Eligible patients were 1:1 randomized to receive either SXT or 2GC for the initial 6-month period (1 course), then switched to the other antimicrobial agent class for the subsequent course, with switching continuing after each course until the end of the study. Urethral orifice cultures (UOCs) were obtained at the time of switching antimicrobial prophylaxis. RESULTS: Among 97 children (mean age 13.6 months) on prophylaxis, breakthrough UTIs occurred during 13.3 % (10/75) of SXT courses and 10.3 % (8/78) of 2GC courses (p = 0.62). 2GC failed earlier than SXT (mean ± standard error: 0.81 ± 0.1 vs. 2.37 ± 0.36 months, respectively; p = 0.028). Pseudomonas aeruginosa and Enterococcus spp. were more frequently isolated after 2GC courses than after SXT courses [22.6 vs. 4.8 % (p = 0.02) and 20.7 vs. 4.8 % (p = 0.035), respectively]. Prophylaxis with 2GC significantly increased resistance to both 2GC and SXT, while SXT prophylaxis did not affect susceptibility to 2GC. CONCLUSIONS: While SXT and 2GC appear to be equally efficacious as UTI prophylaxis in children, the latter exert a broader effect on patients' flora and development of bacterial resistance, suggesting that SXT may be more appropriate for UTI prophylaxis than 2GC.

Longitudinal assessment of bone quality in pediatric patients with chronic kidney disease in relation to treatment modality.

Children with chronic kidney disease (CKD) are at high risk of developing impaired bone quality. Our aim was to investigate changes of bone quality in children with CKD in relation to their treatmant using two imaging techniques-dual energy X-ray absorptiometry and quantitative ultraSonography (QUS). Thirty-three patients with CKD (18 boys and 15 girls, mean age 10.37 ± 3.37 years) were evaluated with bone mineral density (BMD) measured by DXA at the lumbar spine and hip and with speed of sound (SOS) measured by QUS at the radius and tibia at the beginning and at the end of the study. The patient cohort consisted of 14 patients with CKD stage 3-4 not treated with dialysis (CKD group), 5 patients on peritoneal dialysis treatment (PD group) and 14 patients after kidney transplantation (RTx group). BMD measurements did not show any significant changes in CKD and PD patients during the study. There was a reduction in BMD measured at the lumbar spine, femoral neck and total hip in RTx patients that was approaching significance. During the 2-year follow-up, SOS measurements at the radius decreased significantly in PD patients, whereas SOS measurements at the tibia significantly improved in RTx patients. No significant changes in QUS parameters were recorded for patients in the CKD group. In conclusion, our study shows that QUS parameters seem to better reflect the state of hyperparathyroidism of renal osteodystrophy as they deteriorate significantly in patients on dialysis and improve after renal transplantation.

X-linked hypophosphatemia due to a de novo novel splice-site variant in a 7-year-old girl with scaphocephaly, Chiari syndrome type I and syringomyelia.

X-linked hypophosphatemia (XLH) is a rare X-linked dominant inherited disorder caused by loss-of-function variants in the PHEX gene and characterized by renal phosphate wasting, hypophosphatemia, abnormal vitamin D metabolism, growth retardation and lower limb deformities. We describe a case of XLH-rickets in a 7-year-old girl with scaphocephaly, Chiari syndrome type I and syringomyelia, with a de novo non-canonical splice variant (c.1080-3C > G) in intron 9 of the PHEX gene, that has not been previously described.

Prevalence of masked hypertension and its association with left ventricular hypertrophy in children and young adults with chronic kidney disease: a systematic review and meta-analysis.

OBJECTIVES: There are limited studies using ambulatory blood pressure monitoring (ABPM) to assess blood pressure (BP) status in young patients with chronic kidney disease (CKD) on dialysis or after kidney transplantation. The aim of this meta-analysis is to estimate the prevalence of both white-coat hypertension (WCH) and masked hypertension, along with the prevalence of left ventricular hypertrophy (LVH), in children and young adults with CKD on dialysis or after kidney transplantation. METHODS: We performed a systematic review and meta-analysis of observational studies assessing the prevalence of BP phenotypes using ABPM, in children and young adults with CKD stages 2-5d. Records were identified by search in databases (Medline, Web of Science, CENTRAL) and sources of grey literature, until 31 December 2021. A random-effects meta-analysis of proportions (double arcsine transformation) was conducted. RESULTS: Ten studies were included in the systematic review, reporting data from 1140 individuals (children and young adults with CKD with a mean age of 13.79 ±â€Š4.35 years). Masked hypertension and WCH were diagnosed in 301 and 76 patients, respectively. It was estimated an overall pooled masked hypertension prevalence of 27% [95% confidence interval (95% CI) 18-36, I2  = 87%] and an overall pooled WCH prevalence of 6% (95% CI 3-9, I2  = 78%). Among kidney transplant recipients, masked hypertension had a prevalence of 29% (95% CI 14-47, I2  = 86%). The prevalence of LVH was found 28% (95% CI 0.19-0.39) in a total of 238 CKD patients with ambulatory hypertension. In 172 CKD patients with masked hypertension, LVH was present in 49, with the estimated prevalence being 23% (95% CI 0.15-0.32). CONCLUSION: Masked hypertension has a significant prevalence in children and young adults with CKD. Masked hypertension carries an adverse prognosis, with an increased risk of LVH, warranting clinical attention when assessing cardiovascular risk in this population. Therefore, ABPM and echocardiography is of high importance when assessing BP status in children with CKD. PROTOCOL REGISTRATION NUMBER DOI: 10.17605/OSF.IO/UKXAF.

Severe hypophosphataemia can be an early sign of osteopetrorickets: a case report.

Osteopetrorickets is a rare complication of autosomal recessive ("malignant") osteopetrosis. Its prompt diagnosis is essential, because early suspicion of infantile osteopetrosis enables treatment with human stem cell transplantation, depending on the gene involved. It is important to identify not only the characteristic radiological changes of rickets, but also the coexistence of increased bone density, so as not to miss this very rare entity. Herein, a brief case report is presented.

Comparison of the 2017 American Academy of Pediatrics with the fourth report and the 2016 European Society of Hypertension guidelines for the diagnosis of hypertension and the detection of left ventricular hypertrophy in children and adolescents: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: In 2017, the American Academy of Pediatrics (AAP) recommended new blood pressure (BP) thresholds for the diagnosis of hypertension in children and adolescents. We assessed the impact of the AAP guideline, as compared to the Fourth Report and the 2016 European Society of Hypertension guidelines (ESH), on the prevalence of hypertension and the detection of left ventricular hypertrophy (LVH). METHODS: We systematically searched for studies evaluating the impact of the 2017 AAP guidelines on the prevalence of hypertension and LVH compared with the Fourth Report or the 2016 ESH guidelines. Meta-analysis was performed to compare the overall risk of LVH between the guidelines. We used a random-effects model to synthesize quantitative data. RESULTS: We included 18 observational studies in the systematic review with an overall moderate to high risk of bias. The AAP guideline identified more children with hypertension than the Fourth Report and the ESH guidelines. In the meta-analysis of three observational studies, the guidelines revealed similar associations with LVH [odds ratio (OR) = 3.89, 95% confidence interval (95% CI) 1.68-8.99 for AAP and OR = 3.19, 95% CI 1.14-8.88 for Fourth Report/ESH guidelines]. Qualitative analysis of two observational studies revealed similar predictive value of the guidelines for LVH in adult life. CONCLUSION: Despite the higher prevalence of hypertension frequently reported by the adoption of AAP guideline BP thresholds compared with Fourth Report and the ESH guidelines, the new thresholds have not been proved to advance assessment of cardiovascular risk in terms of LVH currently the most accepted subclinical marker in youth.

Arterial stiffness and nocturnal hypertension in preterm children and adolescents.

BACKGROUND AND OBJECTIVES: Preterm birth has been associated with increased risk for developing hypertension and other chronic diseases during childhood and adulthood. The aim of the current prospective case-control study was to investigate the associations of preterm birth with ambulatory blood pressure (BP) levels and arterial stiffness during childhood and adolescence. METHODS: The study population included 52 children and adolescents born preterm and 26 healthy children born full term with similar age. The participants underwent ambulatory BP monitoring (ABPM) and assessment of carotid-femoral pulse wave velocity (PWV). RESULTS: Preterm children presented higher night SBP z score values compared to controls, but did not differ in other ABPM parameters, office peripheral and central SBPs. Nocturnal hypertension was found in 78% (7/9) of ex-preterm children with ambulatory BP hypertension. Preterm birth was an independent predictor of PWV z score adjusted for heart rate. Estimated marginal means for PWV z score adjusted for age, sex, presence of kidney disease at birth, office BPs, night BPs, central SBP, and BMI z scores were significantly higher in preterm individuals compared to controls (0.703, 95% confidence interval [CI] 0.431-0.975 versus -0.19, 95% CI -0.574-0.536, respectively, P  = 0.027). Preterm children who were overweight presented the highest values of night SBP and PWV z score. CONCLUSION: Preterm birth is associated with higher nocturnal BP and increased arterial stiffness in childhood and adolescence. Increased awareness for detection of hypertension and prevention of obesity in childhood could prevent future adverse cardiovascular outcomes in preterm individuals.

Comparative study of quantitative ultrasonography and dual-energy X-ray absorptiometry for evaluating renal osteodystrophy in children with chronic kidney disease.

Our aim was to assess bone parameters in children with chronic kidney disease (CKD) with both dual-energy X-ray absorptiometry (DXA) and quantitative ultrasonography (QUS) and additionally with biochemical markers of bone turnover. Twenty children (12 boys and 8 girls) with CKD and a mean decimal age of 9.47 ± 4.44 years were included in the study where anthropometric parameters (height and weight), pubertal status, bone mineral density (BMD) at lumbar spine, speed of sound (SOS) measured by QUS at radius and at tibia, and biochemical markers of bone metabolism were measured. Six patients (30%) had tibial SOS Z score <-1, and 52.7% had radial SOS Z score <-1, whereas only 16.67% had BMD Z score <-1. Patients had significantly increased levels of serum intact parathormone (p < 0.001), serum bone alkaline phosphatase (BAP) (p < 0.001) and serum N-terminal-mid fragment (aminoacids 1-43) of osteocalcin (p < 0.001) compared to controls, whereas serum osteoprotegerin was significantly decreased in patients compared to controls (p = 0.001). SOS was significantly correlated to BAP (r = -0.586, p = 0.013 and r = -0.709, p = 0.001, respectively, for radius and tibia). In conclusion no association between DXA and QUS measurements was documented in our study, whereas QUS was better correlated to biochemical indices of ROD.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) due to AIRET16M mutation in a consanguineous Greek girl.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) or autoimmune polyendocrine syndrome type 1 (APS-1) is a rare autosomal recessive disease caused by mutations of the AutoImmune REgulator (AIRE) gene, an important mediator of tolerance to self-antigens. It is characterized by two out of three major components: chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. We present an 11-year-old girl suffering from recurrent episodes of mucocutaneous candidiasis and onychomycosis from 1 to 6 years of age, and transient alopecia at the age of 4 years. Hypoparathyroidism and dental enamel hypoplasia were diagnosed at 8 years. Autoantibodies to thyroid and adrenal glands were not detected and all other endocrine functions have remained normal. Genetic analysis revealed that the patient was homozygous for the mutation T16M in exon 1 of the AIRE gene (p.T16M, c.47C>T). This is the first APECED case reported for carrying this mutation in homozygous form. Parents were third cousins and heterozygous carriers of this mutation.

Arterial stiffness in children and adolescents with masked and sustained hypertension.

This study recruited 85 healthy children and adolescents, aged 6-18 years, from a school-based blood pressure (BP) screening study and performed office BP measurements, 24-h ambulatory blood pressure monitoring (24-h ABPM) and 24-h pulse wave analysis. Prevalence of BP phenotypes was assessed, factors that may predict hypertension (HTN) in ABPM were examined and the effect of BP phenotypes, as well as school, office, and ambulatory BP parameters on pulse wave velocity (PWV), was investigated. Forty-five (54.9%) of the children were normotensives, 8 (9.7%) were white coat hypertensives (WCH), 19 (23.2%) had masked hypertension (MH), and 10 (12.2%) had sustained HTN. Estimated adjusted marginal means for 24-h PWV were 4.79 m/s (95% CI 4.65-4.94) for sustained hypertensives, 4.72 m/s (95% CI 4.62-4.82) for MH, 4.38 m/s (95% CI 4.23-4.54) for WCH, and 4.33 m/s (95% CI 4.26-4.40) for normotensives (sustained hypertensives versus normotensives and WCH, p < 0.001, MH versus normotensives and WCH, p < 0.005). Neither body mass index (BMI) z-score nor school systolic BP (SBP) z-score could predict HTN by ABPM. Office SBP z-score was associated with 1.74 times increased odds ratio to have HTN in ABPM. Sustained HTN and MH were independent predictors of 24-h PWV after adjustment for age, sex, and BMI z-score. In conclusion, arterial stiffness in children and adolescents was assessed by 24-h PWV associates with mean ambulatory BP. Both school and office BP measurements could not predict HTN in ABPM or increasing PWV. HTN in ABPM was independently associated with the risk of higher PWV compared with normotensive and WCH phenotype.