Serum angiopoietin-2: a promising biomarker for early diabetic kidney disease in children and adolescents with type 1 diabetes.

Albuminuria has been considered the golden standard biomarker for diabetic kidney disease (DKD), but appears once significant kidney damage has already occurred. Angiopoietin-2 (Angpt-2) has been implicated in the development and progression of DKD in adults. We aimed to explore the association of serum Angpt-2 levels with DKD in children and adolescents with type 1 diabetes mellitus (T1DM) of short duration (3-5 years) and to evaluate the predictive power of serum Angpt-2 in the early detection of DKD prior to the microalbuminuric phase. The current cross-sectional study included 90 children divided into three age and sex-matched groups based on urinary albumin-to-creatinine ratio (UACR): microalbuminuric diabetic group (n = 30), non-albuminuric diabetic group (n = 30), and control group (n = 30). All participants were subjected to anthropometric measurements, serum Angpt-2 and fasting lipid profile (total cholesterol, triglycerides, LDL-C, HDL-C, and Non-HDL-C) assessment. Glomerular filtration rate was estimated based on serum creatinine (eGFR-Cr). Higher serum Angpt-2 levels were detected in both diabetic groups compared to controls and in microalbuminuric compared to non-albuminuric diabetic group. There was no detected significant difference in eGFR-Cr values across the study groups. Serum Angpt-2 was positively correlated with triglycerides, LDL, Non-HDL-C, HbA1c, and UACR, while UACR, HbA1c, and Non-HDL-C were independent predictors for serum Angpt-2. Serum Angpt-2 at level of 137.4 ng/L could discriminate between microalbuminuric and non-albuminuric diabetic groups with AUC = 0.960 and at level of 115.95 ng/L could discriminate between the non-albuminuric diabetic group and controls with AUC = 0.976.Conclusion: Serum Angpt-2 is a promising potent biomarker for the detection of early stage of DKD in childhood T1DM before albuminuria emerges. What is Known? • Urine albumin-to-creatinine ratio (UACR) and glomerular filtration rate (GFR) are the golden standard but late biomarkers for DKD. • Angiopoietin-2 has been implicated in the development and progression of DKD in adults with diabetes, but has not been explored in T1DM children with DKD. What is New? • Higher serum angiopoietin-2 was detected in diabetic groups compared to controls and in microalbuminuric compared to non-albuminuric group. • Angiopoietin-2 correlated positively with triglycerides, LDL, Non-HDL-C, HbA1c, and UACR. • Serum angiopoietin-2 is a promising early diagnostic biomarker for DKD in children with T1DM.

Serum apelin-12 and obesity-related markers in Egyptian children with Down syndrome.

Children with Down syndrome (DS) exhibit higher overweight/obesity rates than their typically developing peers. Apelin-12 is a bioactive adipokine that exerts vital roles in obesity-related cardiometabolic comorbidities. To date, apelin-12 has not been investigated in obese-DS. This study aimed to explore the possible association between serum apelin-12 and obesity-related markers and to evaluate the efficiency of apelin-12 in the prediction of metabolic syndrome (MetS) in obese-DS compared to BMI Z-score matched obese-control. The cross-sectional study included 150 prepubertal children classified into three groups; obese-DS (n = 50), obese-control (n = 50), and normal-weight-control (n = 50). Anthropometric parameters, body adiposity, fasting serum levels of blood glucose (FBG), insulin, lipid profile, and apelin-12 were evaluated. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from FBG and insulin. MetS was defined using Adult Treatment Panel III criteria modified for the pediatric age group. ROC curves were analyzed to evaluate the efficiency of apelin-12 in predicting MetS in obesity groups. Obese-DS exhibited higher body adiposity with marked central fat distribution, atherogenic lipid profile, and higher HOMA-IR compared to obese-control. Apelin-12 was significantly higher in obese-DS and obese-DS with MetS compared to obese-control and obese-control with MetS respectively (p < 0.001). The increase in apelin-12 with higher obesity grades was pronounced in obese-DS. Apelin-12 strongly correlated with body adiposity, several MetS risk factors, and HOMA-IR in obese-DS. Significantly higher AUC for apelin-12 in the diagnosis of MetS among obese-DS than obese-control (AUC = 0.948 vs. AUC = 0.807; p = 0.04). CONCLUSIONS:  The current study supports the crucial role of apelin-12 in obesity-related clinical and biochemical markers and in MetS in obese-DS and obese-control. Serum apelin-12 is a potential diagnostic biomarker for MetS with greater performance in obese-DS than obese-control raising its potential for clinical and therapeutic applications. WHAT IS KNOWN: • Obese-DS children displayed excess body adiposity, Pronounced central fat distribution, atherogenic lipid profile, higher HOMA-IR, and higher prevalence of MetS than obese-control. WHAT IS NEW: • Higher serum apelin-12 was observed in obese-DS and obese-DS with MetS than obese-control and obese-control with MetS respectively. The increase in apelin-12 level with increasing obesity grades was more pronounced in obese-DS. • Apelin-12 strongly correlated with obesity-related markers and MetS components in obese-DS. Apelin-12 performed better as a diagnostic biomarker for MetS in obese-DS than obese-control.

Trabecular Bone Score in Assessing Bone Mineralization Status in Children with End- Stage Renal Disease: A Promising Tool.

Areal-bone mineral density (aBMD) of lumbar-spine dual energy X-ray absorptiometry (DXA) scan is the most frequently used tool in evaluating BMD in pediatric patients, however its size dependency have significant impact on measurements accuracy in children with chronic kidney disease (CKD). This study aimed to evaluate the usefulness of trabecular bone score (TBS) computed during lumbar-spine DXA scan in assessing bone status in children on maintenance hemodialysis (HD). Ninety-three children on HD (aged 9-18 years) were subjected to lumbar-spine DXA-scan to obtain aBMD (g/cm2) and TBS.Z-scores of aBMD for chronological-age (aBMDZ-CA), height-age (aBMDZ-HA), and TBSZ-score were calculated using mean and SD values of 442 healthy controls. aBMD and TBS were significantly lower in short-for-age and normal height-for-age patients compared to the corresponding values of controls (p < 0.05 for all). Degraded vertebral microarchitecture (TBSZ-score < -2) was detected in 48% and 44% of male and female patients respectively. There were no significant differences in median TBSZ-score between short-for-age and normal height-for-age HD patients in male (p = 0.425) and in female (p = 0.316) patients. TBSZ-score correlated significantly with aBMDZ-CA (r = 0.234; p = 0.024) but not with aBMDZ-HA (r = 0.077; p = 0.462). Patients with history of fractures (5 patients only) had significantly lower TBS scores compared to those without fracture history (p = 0.016). CONCLUSION: TBS is significantly reduced in children on maintenance HD and is associated with increased fracture incidence. TBS has shown to be a promising tool in assessing bone quality (trabecular microarchitecture) in children with CKD being not size-dependent as is a-BMD, for further evaluation of its potential role in therapeutic and follow-up decisions. WHAT IS KNOWN: • In children with CKD, bone demineralization starts as early as CKD stage 2, so assessment of bone health is mandatory for follow up and therapeutic decisions. • aBMD of lumbar-spine DXA scan is the most used tool in evaluating BMD in pediatric patients, however its size dependency have significant impact on measurements made in children with CKD. WHAT IS NEW: • TBS is significantly reduced in children on maintenance HD and associated with increased fracture incidence. • TBS has shown to be a promising tool in assessing bone quality (trabecular microarchitecture) in children with CKD being not size-dependent as is a-BMD.

The relevance of left ventricular functions to clinical and metabolic characteristics of prepubertal children with obesity.

BACKGROUND: Paediatric obesity is a worldwide health burden, with growing evidence linking obesity to myocardial function impairments. The study aims to evaluate left ventricular functions among prepubertal obese children to obesity-related clinical and metabolic parameters. METHODS: Between June 2019 and March 2020, 40 prepubertal children with obesity were recruited and compared to 40 healthy controls. Patients were assessed for body mass index z scores, waist circumference, body adiposity by bioimpedance analysis, and obesity-related laboratory tests, for example, serum chemerin. Left ventricular functions were assessed using variable echocardiographic modalities, such as M-mode, tissue Doppler, and two-dimensional speckle tracking. RESULTS: Mean patients' age was 9.25 ± 1.05 years. Left ventricular mass index, E/E', and myocardial performance index were significantly increased in obese children than controls. Although M-mode-derived ejection fraction was comparable in both groups, two-dimensional speckle tracking-derived ejection fraction, global longitudinal strain, and global circumferential strain were significantly lower in cases than controls. Left ventricular mass index displayed a positive correlation with body mass index z score (p = 0.003), fat mass index (p = 0.037), and trunk fat mass (p = 0.021). Global longitudinal strain was negatively correlated with body mass index z score (p = 0.015) and fat mass index (p = 0.016). Serum chemerin was positively correlated with myocardial performance index (p = 0.01). CONCLUSION: Alterations of left ventricular myocardial functions in prepubertal obese children could be detected using different echocardiographic modalities. Chemerin, body mass index z score, fat mass index, and trunk fat mass were correlated with subclinical left ventricular myocardial dysfunction parameters before puberty. Our results reinforce early and strict management of childhood obesity upon detection of changes in anthropometric and body adiposity indices.

Serum adiponectin, body adiposity and metabolic parameters in obese Egyptian children with Down syndrome.

OBJECTIVES: Children with Down syndrome (DS) have a higher risk for obesity. Adiponectin plays a crucial role in obesity-related cardiometabolic comorbidities. The study aimed to explore whether body adiposity indicators, the frequency of metabolic syndrome (MetS) and its components, serum adiponectin and insulin resistance indices as well as the validity of serum adiponectin as a biomarker for MetS are different in prepubertal obese-DS children compared to matched obese-controls. METHODS: Cross-sectional study included 150 prepubertal children classfied into three groups; obese-DS (n=50), obese-control (n=50) and normal-weight-control (n=50). Participants were evaluated for waist-circumference (WC), body adiposity, serum triglycerides, HDL-C, adiponectin and Homeostasis-Model-Assessment of Insulin-Resistance (HOMA-IR). MetS was defined using modified Adult Treatment Panel III-criteria. RESULTS: Obese-DS had significantly higher WC, %body fat, total-fat mass, trunk-fat mass, trunk/appendicular-fat mass ratio, triglycerides, insulin and HOMA-IR and significantly lower HDL-C values compared to obese-control. Higher prevalence of MetS and its components were observed in obese-DS that was evident at younger age. Adiponectin was significantly lower in obese-DS compared with obese-control and in obese-DS children with MetS compared to obesecontrol with MetS. The decrease in adiponectin with increasing grades of obesity was pronounced in obese-DS. Adiponectin exhibited strong correlations with body adiposity, several MetS components and HOMA-IR in obese-DS. Adiponectin performed better as a biomarker for MetS among obese-DS (AUC=0.808) than obese-control (AUC=0.674). CONCLUSIONS: Prepubertal obese-DS displayed excess body adiposity with pronounced central fat distribution, atherogenic lipid profile and higher insulin resistance compared to matched obese-control. Adiponectin performed better as potential biomarker of MetS in obese-DS than obese-control.

Genetic and clinical heterogeneity of permanent neonatal diabetes mellitus: a single tertiary centre experience.

AIMS: Neonatal diabetes mellitus (NDM) is a rare disease where diabetes presents during the first six months of life. There are two types of this disorder: permanent neonatal diabetes (PNDM) and transient neonatal diabetes mellitus (TNDM). PNDM occurs due to mutations in genes involved in either beta-cell survival, insulin regulation, and secretion. This study aims to define the genetic aetiology and clinical phenotypes of PNDM in a large Egyptian cohort from a single centre. METHODS: Patients with PNDM who were diagnosed, treated, or referred for follow-up between January 2002 and January 2021 were identified and clinically phenotyped. All patients were tested for mutations in EIF2AK3, KCNJ11, ABCC8, INS, FOXP3, GATA4, GATA6, GCK, GLIS3, HNF1B, IER3IP1, PDX1, PTF1A, NEUROD1, NEUROG3, NKX2-2, RFX6, SLC2A2, SLC19A2, STAT3, WFS1, ZFP57 using targeted next-generation sequencing (NGS) panel. INSR gene mutation was tested in one patient who showed clinical features of insulin resistance. RESULTS: Twenty-nine patients from twenty-six families were diagnosed with PNDM. Pathogenic variants were identified in 17/29 patients (59%). EIF2AK3, INS, and KATP channel mutations were the commonest causes with frequency of 17%, 17%, and 14%, respectively. Patients with ABBC8 and KCNJ11 mutations were successfully shifted to sulfonylureas (SU). Paired data of glycosylated haemoglobin before and after SU transfer showed improved glycaemic control; 9.6% versus 7.1%, P = 0.041. CONCLUSIONS: PNDM is a heterogenous disease with variable genotypes and clinical phenotypes among Egyptian patients. EIF2AK3, INS, ABCC8, and KCNJ11 mutations were the commonest causes of PNDM in the study cohort. All patients with KATP channel mutations were effectively treated with glyburide, reflecting the fact that genetic testing for patients with NDM is not only important for diagnosis but also for treatment plan and prognosis.

Size-adjustment techniques of lumbar spine dual energy X-ray absorptiometry measurements in assessing bone mineralization in children on maintenance hemodialysis.

OBJECTIVES: Growing skeleton is uniquely vulnerable to impaired mineralization in chronic kidney disease (CKD). Continued debate exists about the optimal method to adjust for body size when interpreting dual energy X-ray absorptiometry (DXA) scans in children with CKD given the burden of poor growth. The study aimed to evaluate the clinical usefulness of size-adjustment techniques of lumber-spine DXA measurements in assessing bone mineralization in children with kidney failure on maintenance hemodialysis (HD). METHODS: Case-control study included 93 children on maintenance HD (9-18 years; 48 males). Participants were subjected to spinal-DXA-scan to obtain areal bone mineral density (aBMD; g/cm2). Volumetric-BMD (vBMD; g/cm3) was mathematically estimated. Z-scores of aBMD for chronological age (aBMDZ-CA), aBMD adjusted for height age (aBMDZ-HA), and vBMDZ-score were calculated using mean and SD values of age subgroups of 442 healthy controls (7-18 years). RESULTS: In short-for-age CKD patients, aBMDZ-CA was significantly lower than vBMDZ-score, while aBMDZ-HA was significantly higher than aBMDZ-CA and vBMDZ-score. In normal height-for-age CKD patients, no significant difference between aBMDZ-scores and vBMDZ-score was detected. aBMDZ-CA was significantly lower and aBMDZ-HA was significantly higher in short-for-age compared to normal height-for-age patients without significant differences in vBMDZ-score. We observed age-related decrements in the percentage of HD patients with normal densitometric Z-scores, the effect of age was less pronounced in aBMDZ-HA than vBMDZ-score. vBMDZ-score correlated negatively with age, but not with heightZ-score. CONCLUSIONS: Estimated vBMD seems to be a convenient size-adjustment approach of spinal-DXA measurements in assessing BMD especially in older short-for-age children with CKD. aBMDZ-CA underestimates, while aBMDZ-HA overestimates BMD in such patients.

Epicardial and Perihepatic Fat as Cardiometabolic Risk Predictors in Girls with Turner Syndrome: A Cardiac Magnetic Resonance Study

Objective: Turner syndrome (TS) patients are at high risk of cardiometabolic disorders. Cardiometabolic risk factors are more commonly related to visceral rather than total body adiposity. Adipocytokines have been explored as a potential link between obesity and obesity-related cardiometabolic dysfunction. This study explored the validity of epicardial fat-thickness (EFT) and perihepatic fat-thickness (PHFT) measurement as cardiometabolic-risk predictors in TS-girls in relation to standard obesity-indices and metabolic syndrome (MetS) components. Methods: Forty-six TS girls and twenty-five controls (10-16 years) were subdivided into two age-groups (10 to less than 13 and 13-16). Participants were assessed for body mass index (BMI) Z-scores, waist circumference (WC), total-fat mass (FM) and trunk-FM by bioimpedance-technique, EFT and PHFT by cardiovascular magnetic resonance, lipid-profile, homeostasis model assessment of insulin resistance (HOMA-IR), and serum chemerin. MetS was defined according to International Diabetes Federation criteria. Results: Overweight/obesity and MetS were detected in 45.7% and 37% of TS-girls respectively. BMI Z-score, WC, total-FM, trunk-FM, EFT and PHFT values were significantly higher in TS-age groups compared to age-matched control groups, being more pronounced in the older group when TS-girls had been exposed to estrogen. Dyslipidemia, higher HOMA-IR, chemerin, EFT and PHFT values were observed in lean-Turner compared to BMI-Z-matched controls. EFT and PHFT were significantly correlated with chemerin and several components of MetS. EFT at a cut-off-value of 6.20 mm (area under the curve=0.814) can predict MetS in TS-girls. Conclusion: TS-girls displayed an adverse cardiometabolic profile during late childhood and adolescence. EFT and PHFT are emerging cardiometabolic risk predictors in TS-patients. Excess EFT rather than total body adiposity may contribute to altered metabolic profile among lean-Turner patients.

Association between Toxoplasma gondii infection and metabolic syndrome in obese adolescents: A possible immune-metabolic link.

Background Toxoplasmosis as a global disease is considered as a triggering factor responsible for development of several clinical diseases. However, Toxoplasma gondii (T. gondii) is an understudied parasite of potential interest in obesity research. The current study aimed to explore the role of latent T. gondii infection in the pathogenesis of metabolic syndrome (MetS) in obese adolescents through studying the relationship between serum interferon-gamma [IFN-γ] and serum chemerin in context of MetS components. Methods Eighty-three obese adolescents were serologically screened for T. gondii-IgG antibodies and compared to 35 age-matched healthy T. gondii-seronegative controls. Participants were evaluated for anthropometric measurements, total-fat mass [FM], trunk-FM, serum lipid profile, IFN-γ, and chemerin levels. Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated. Results The prevalence of MetS was significantly higher within obese T. gondii-seropositive group compared to obese T. gondii-seronegative group (P = 0.033). Seropositive obese MetS group displayed significantly higher trunk-FM, HOMA-IR, chemerin, and IFN-γ compared to seronegative obese MetS group. Serum chemerin and IFN-γ were strongly correlated (P < 0.001) and were positively correlated with BMI, WC, total-FM, trunk-FM, HOMA-IR, cholesterol, triglycerides and negatively correlated with HDLC. HOMA-IR was a common predictor for serum chemerin (P = 0.030) and IFN-γ (P < 0.001). Conclusions The study results suggest that T. gondii infection may exert an immune-metabolic effect that may have a potential role in the development of MetS among obese adolescents.

Genetic association between interleukin-10 gene rs1518111 and rs3021094 polymorphisms and risk of type 1 diabetes and diabetic nephropathy in Egyptian children and adolescents.

OBJECTIVE: Genetic and environmental factors have been implicated in etiopathogenesis and progression of type 1 diabetes mellitus (T1DM) and diabetic nephropathy (DN). Genetic association between interleukin-10 (IL-10) single nucleotide polymorphisms (SNPs) with T2DM and DN was recently established. We aimed to explore the potential genetic risk of IL-10 gene rs1518111 and rs3021094 SNPs in susceptibility to T1DM and DN. RESEARCH DESIGN AND METHODS: Cross-sectional study included 140 T1DM children, of whom 74 had DN and 90 controls. IL-10 gene rs1518111 and rs3021094 SNP were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique of the extracted genomic DNA from participants. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to explore the association between IL-10 gene polymorphisms and the risk of T1DM and DN. RESULTS: For rs1518111 SNP, AA genotype was associated with high risk of T1DM (OR = 4.53; CI = 2.11-9.74; p < 0.001), while A allele was associated with high risk of both T1DM (OR = 3.35; CI = 2.20-5.09; p < 0.001) and DN (OR = 2.36; CI = 1.27-4.38; p = 0.006). For rs3021094 SNP, AC genotype displayed lower risk to develop T1DM (OR = 0.35; CI = 0.13-0.94; p = 0.037), while A allele displayed higher risk to develop T1DM (OR = 1.69; CI = 1.11-2.56; p = 0.013). GA and AC haplotypes of rs1518111 and rs3021094 had lower ORs for having T1DM and DN, while GC had lower OR for having T1DM. CONCLUSIONS: AA genotype and A allele of IL-10 rs1518111 SNP could be linked to increased risk for T1DM and DN among Egyptian children. None of rs3021094 genotypes or alleles displayed significant association with DN. GA and AC haplotypes could be protective against T1DM and DN susceptibility.

Prepubertal gynecomastia is not always idiopathic: case series and review of the literature.

Although pubertal gynecomastia is a common clinical presentation of adolescent males, prepubertal gynecomastia is uncommon and mostly idiopathic. However, pathological causes of prepubescent gynecomastia are encountered in clinical practice. This manuscript carries an important message to general pediatricians, to care about exclusion of pathological causes for every patient of prepubertal gynecomastia. We present four different patients with pathological gynecomastia. One of them revealed to be secondary to Sertoli cell tumor, while the second patient describes trauma as a rare cause of prepubertal true gynecomastia. To the best of our knowledge, this is the first time to report occupational trauma as a cause of true gynecomastia as confirmed by pathological specimen, in a prepubertal boy. The third patient presented with retro-areolar mass and bloody nipple discharge secondary to mammary duct ectasia and had favorable self-limited course. Hyperprolactinemia secondary to neglected congenital hypothyroidism was the cause beyond gynecomastia in the fourth patient and this cause has been reported only once in the literature.Conclusion: Despite being rare, pathological causes of prepubertal gynecomastia are encountered in clinical practice, and full investigations including breast and testicular ultrasound are needed to exclude any pathology before diagnosing idiopathic gynecomastia. Repeated friction of the breast can lead to true gynecomastia not only to pseudogynecomastia as previously known. What is Known: • It has been reported that trauma can cause pseudogynecomastia due to hematoma or fat necrosis. • Prepubertal gynecomastia is mostly idiopathic. What is New: • Long-term breast trauma can cause true gynecomastia (adenosis). • Although being mostly idiopathic, pathological causes of prepubertal gynecomastia must be ruled out.

Effect of tactile/kinesthetic massage therapy on growth and body composition of preterm infants.

Massage therapy (MT) improves growth parameters in preterm infants. The growth of lean mass rather than fat mass has been associated with better long-term outcomes. We aimed to study the effect of tactile/kinesthetic MT on growth and body composition parameters in preterm infants. Preterm (< 32 weeks gestation) infants were randomly assigned at corrected gestational age of 35 weeks to receive 3 consecutive, 15-min, sessions of MT over 5 days or routine care. Primary outcome was mean daily weight gain. Secondary outcomes included anthropometric measurements and body composition parameters assessed by dual X-ray absorptiometry (DXA) scan. Out of 218 infants screened, 86 were eligible and 60 infants (30 in each group) were recruited after parental consent. MT was associated with significant increase in daily weight gain [19.3 (10-34.3) versus 6.2 (2.5-18.4) g/day, p = 0.01] and growth velocity [12.5 (6-21) versus 3.6 (1.6-12.6) g/kg/d, p = 0.01] compared with routine care. Infants on MT showed significant increase in total body mass, fat mass (total/legs), lean mass (total/arms/legs/trunk), and bone mineral density (arms/legs/trunk) values compared with routine care group. In conclusions, MT improves growth quality as evident by increased total and regional lean masses, increased bone mineral density, and peripheral rather than central fat distribution. What is known on this subject? • Massage therapy (MT) for preterm infants leads to achievement of faster independent oral feeding, increased weight gain, less stress, less response to pain, less occurrence of sepsis, and shorter hospital stay. • Growth of lean mass rather than fat mass has been associated with better long-term outcomes. What this study adds? • Tactile/kinesthetic massage therapy in preterm infant is associated with improved growth parameters and anthropometric measures. • Tactile/kinesthetic massage therapy increased total body mass, fat mass (total/legs), lean mass (total/arms/legs/trunk), and bone mineral density (arms/legs/trunk) values.

Urinary Cyclophilin A and serum Cystatin C as biomarkers for diabetic nephropathy in children with type 1 diabetes.

BACKGROUND: Currently, microalbuminuria is the gold standard for detection and prediction of diabetic nephropathy (DN). However, microalbuminuria appears once significant kidney damage has actually occurred. OBJECTIVES: We investigated the diagnostic role of urinary Cyclophilin-A (uCypA), uCypA/creatinine ratio (uCypA/Cr) and serum Cystatin-C (sCysC) as biomarkers for early detection of DN in children with type 1 diabetes mellitus (T1DM) of short duration (2-5 years) before microalbuminuria emerges. METHODS: uCypA, uCypA/Cr, and sCysC levels were assessed in three age- and sex-matched groups; microalbuminuric diabetic group (n = 31), normoalbuminuric diabetic group (n = 29), and control group (n = 30). Glomerular filtration rate was estimated (eGFR) based on both serum creatinine (eGFR-Cr) and sCysC (eGFR-CysC). RESULTS: Significantly higher sCysC and lower eGFR-CysC were detected in both diabetic groups compared to controls and in microalbuminuric compared to normoalbuminuric group. No detected significant difference in eGFR-Cr values across the studied groups. Both uCypA and uCypA/Cr were significantly elevated in microalbuminuric compared to both normoalbuminuric and control groups with no difference between normoalbuminuric and control groups. Prediction of microalbuminuria was conducted using sCysC with area under curve up to 0.980. Combined use of sCysC and uCypA had better diagnostic value than uCypA alone. CONCLUSION: sCysC is a promising early biomarker for DN in childhood T1DM before albuminuria detection. eGFR-CysC is superior to eGFR-Cr in evaluating renal status in childhood T1DM. uCypA and uCypA/Cr were useful tools in predicting microalbuminuria, although not regarded as diagnostic biomarkers for early-stage DN in T1DM children by the current study.

Bone Mineral Status in Children with Epilepsy: Biochemical and Radiologic Markers.

OBJECTIVE: The aim of this study is to assess bone mineral status in children with epilepsy, on different antiepileptic drugs (AEDs) regimen, using dual-energy X-ray absorptiometry (DXA) and routine biochemical bone markers. PATIENTS AND METHODS: This is observational prospective controlled cohort study, conducted at Mansoura University Children Hospital, from January 2014 to June 2015. In this study, we had 152 participants with ages 3-13 years, 70 children diagnosed with epilepsy and 82 were controls. Children classified into two groups according to the duration of treatment, Group 1 children maintained on AEDs for 6-24 months, Group 2 children ≥24 months. Bone mineral density (BMD) measured by DXA and biochemical markers includes serum calcium, phosphorus, alkaline phosphatase (ALP), and parathyroid hormone (PTH). RESULTS: In this study, we found that the serum level of calcium and phosphate were significantly low (P > 0.05) in total cases versus control. We found that the serum level of and ALP and PTH were significantly high (P > 0.05) in total cases versus control. Regarding the DXA markers, there was a significant decrease of BMD and Z-score for the total body and lumbar area in the total cases versus control (P > 0.05). CONCLUSION: The present study showed that all AEDs (new and old) affect bone mineral status in children receiving therapy for more than 6 months, altering both biochemical markers (serum calcium, phosphorus, ALP, and PTH) and radiologic markers (BMD assessed using DXA). Children on AEDs for a longer duration (≥2 years) showed more severe side effects on BMD. Children receiving multiple AEDs are more prone to altered bone mineral status, especially with long duration of therapy. The study also highlights the role of DXA as a safe noninvasive method to assess BMD in children on long-term AEDs.

Pegylated interferon α/ribavirin therapy enhances bone mineral density in children with chronic genotype 4 HCV infection.

BACKGROUND: The impact of chronic hepatitis C (CHC) on bone mineral density (BMD) has been well studied in adults with a relative paucity of data in children, especially concerning effect of treatment with pegylated interferon (PEG-IFN) plus ribavirin (RV). In the current work, we assessed prospectively changes in BMD in children with CHC before, during, and after treatment. METHODS: Forty-six consecutive children with noncirrhotic genotype 4 CHC were subjected to dual-energy X-ray absorptiometry at baseline, 24 weeks, 48 weeks of therapy and 24 weeks after treatment. BMD, bone mineral content (BMC), and Z score of lumbar spine (L2-L4) were reported. Tanner pubertal stage, viral load, liver function tests, serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and liver histopathology were assessed in all included children. RESULTS: Thirty (65.2%) patients had normal BMD, 10 (21.7%) were at risk for low BMD, and 6 (13.1%) had low BMD for chronological age. Patients with low BMD were significantly older (P=0.001), with higher frequency of delayed puberty than other groups (P=0.002). Baseline densitometric parameters (BMD & BMC) were significantly positively correlated with patients' age, weight, height, body mass index and hemoglobin level; while they were insignificantly correlated with basal viral load, histopathology activity index and fibrosis score. Densitometric parameters improved significantly on PEG-IFN plus RV treatment, this improvement was found to be sustainable 24 weeks after therapy. CONCLUSIONS: Low BMD is detectable in a proportion of CHC children. Antiviral therapy leads to a sustainable increase in BMD.

Safety and metabolic impact of Ramadan fasting in children and adolescents with type 1 diabetes.

BACKGROUND: Annually, many children and adolescents with type 1 diabetes mellitus (T1DM) insist on fasting for Ramadan despite being exempted and despite knowing all the risks. We aimed to assess the safety and metabolic impact of Ramadan fasting in children with T1DM using different insulin regimens. METHODS: Children with T1DM who choose to fast during Ramadan 1434/2013 (29 days) were recruited 3 months before Ramadan. They received pre-Ramadan intensive education. Three insulin regimens were included; Regimen-I (regular insulin/NPH); Regimen-II (regular insulin/insulin glargine) and Regimen-III (premixed insulin). Changes in weight, insulin dose, HbA1c, fructosamine and lipid profile were evaluated. RESULTS: Out of total 53 patients (24 male), 28 patients (52.8%) completed Ramadan fasting (fasting group). The remaining 25 patients were included in (broke-fasting group). Positive correlation between fructosamine changes and number of days fasted during Ramadan. Significant decrease in post-Ramadan fructosamine (<0.001) and increase in post-Ramadan total cholesterol and low density lipoprotein (LDL) levels were detected within fasting, broke-fasting and insulin regimen groups. Significant higher blood glucose at three time points, pre-Iftar, pre-Sohur and midday in Regimen-I compared to Regimen-II and Regimen-III (p=0.004). CONCLUSIONS: Fasting during Ramadan is feasible and is associated with significant improvement in fructosamine level in children with T1DM using different insulin regimens. Mandatory consideration to the quality and quantity of food offered to patients with T1DM during Ramadan to guard against adverse changes in lipid profile.

Novel homozygous SLC29A3 mutations among two unrelated Egyptian families with spectral features of H-syndrome.

OBJECTIVES: H syndrome and pigmented hypertrichosis with insulin-dependent diabetes mellitus (PHID) had been described as two autosomal recessive disorders. We aim to screen for pathogenic SLC29A3 mutations in two unrelated Egyptian families with affected siblings of these overlapping syndromes. METHODS: Clinical, laboratory, histopathological, and radiological characteristics of individuals probably diagnosed as H and/or PHID syndrome were reported. Mutation analysis of SLC29A3 gene was performed for all members of the two Egyptian families. RESULTS: All affected individuals were females; proband of family-I (A1961) displayed overlapping features of H syndrome and PHID, while her younger brother (A1962) was asymptomatic. A1961 presented with previously undescribed features; absent pectoralis major muscle and a supracondylar bony spur in left humerus. In family-II, probands (A1965 and A1966) had clinical features consistent with classical H syndrome with unique early onset of cutaneous phenomena at birth. Mutation analysis of SLC29A3 revealed homozygous mutation previously reported in literature c.1279G>A [p.G427S] in A1961 and unexpectedly in the asymptomatic A1962 of family-I. Probands of family-II were homozygous for a novel mutation c.401G>A [p.R134H], in the same codon that was published in an Indian boy [p.R134C]. CONCLUSIONS: We emphasize the inter- and intra-familial genetic heterogeneity among Egyptian patients with overlapping features of SLC29A3 disorders. This suggests the presence of other factors like regulatory genes or epigenetic factors that may explain variable disease manifestations and severity.

Epidemiology of childhood type 1 diabetes mellitus in Nile Delta, northern Egypt - a retrospective study.

OBJECTIVE: The geographical incidence of type 1 diabetes mellitus (T1DM) varies widely worldwide. Both genetic and environmental factors have been implicated, although environmental factors are still speculative and elusive. More epidemiological studies are needed to uncover such factors. To date, there are no reported studies on the epidemiology of childhood T1DM in Nile Delta, Egypt. We aimed to define the incidence, prevalence and demographic characteristics of T1DM in children (0-18 years) living in the Nile Delta region, one of the most densely populated areas in Egypt. METHODS: The study included all T1DM patients aged 0-18 years who lived in the Nile Delta region of Egypt and who were either diagnosed at or referred to Mansoura University Children's Hospital (MUCH) between 1 January 1994 and 31 December 2011. The hospital files of the patients were reviewed. General population data on the 0-18 year age group in the Nile Delta governorates were also presented. RESULTS: From a total of 1600 T1DM patients, 891 (55.7%) were females (p=0.000) and 935 (58.4%) were from rural areas (p=0.000). Calculated age-adjusted incidence of T1DM in 1996, 2006 and 2011 were 0.7, 2.0 and 3.1/10(5)/year, respectively, while calculated age-adjusted prevalence of T1DM in the same years were 1.9, 15.5 and 26.8/10(5)/year, respectively. Patients presented most frequently in the 5-10 year age group (p<0.000) and in winter months (p=0.009). CONCLUSION: In this first childhood T1DM epidemiology study in the Nile Delta region of Egypt, T1DM incidence and prevalence were found to show an increase over the past 18 years (1994-2011). Incidence and prevalence were higher in females and more cases were found to originate from rural areas.

Sporadic Fibrodysplasia Ossificans Progressiva in an Egyptian Infant with c.617G > A Mutation in ACVR1 Gene: A Case Report and Review of Literature.

Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant severe musculoskeletal disease characterized by extensive new bone formation within soft connective tissues and unique skeletal malformations of the big toes which represent a birth hallmark for the disease. Most of the isolated classic cases of FOP showed heterozygous mutation in the ACVR1 gene on chromosome 2q23 that encodes a bone morphogenetic protein BMP (ALK2). The most common mutation is (c.617G > A) leading to the amino acid substitution of arginine by histidine (p.Arg206His). We currently report on an Egyptian infant with a sporadic classic FOP in whom c.617G > A mutation had been documented. The patient presented with the unique congenital malformation of big toe and radiological evidence of heterotopic ossification in the back muscles. The triggering trauma was related to the infant's head, however; neither neck region nor sites of routine intramuscular vaccination given during the first year showed any ossifications. Characterization of the big toe malformation is detailed to serve as an early diagnostic marker for this rare disabling disease.