Assessment of bone mineral density in children with congenital cyanotic heart disease.

BACKGROUND: Cyanotic CHD is one of many disorders in paediatrics that influence the health of children in different clinical aspects. One of the fundamental aspects that may be affected is bone mineral density. OBJECTIVES: The aim of our study is to assess bone mineral density in children with congenital cyanotic heart disease of different anatomical diagnoses. DESIGN/METHODS: Cross-sectional, observational study included 39 patients (20 males) with congenital cyanotic heart disease of different anatomical diagnoses following with the cardiology clinic in Mansoura University children's hospital. All patients were subjected to anthropometric measures, oxygen saturation assessment, and lumber bone mineral density using dual-energy X-ray absorptiometry. RESULTS: Six patients (15.4%) out of the 39 included patients showed bone mineral density reduction, 13 patients (33.3%) showed bone mineral density with Z-score between -1 and -2, while 20 patients (51.3%) showed bone mineral density with Z-score more than -1. CONCLUSION: Low bone mineral density can be found in children with cyanotic CHD, making it important to consider bone mineral density assessment and early treatment if needed to avoid further complications.

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.

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.

Clinical characteristics, outcome, and predictors of neurological sequelae of persistent congenital hyperinsulinism: A single tertiary center experience.

AIM: Congenital hyperinsulinism (CHI) is a heterogeneous disease with variable genetic etiology, histopathology, and clinical phenotype. This study aims to describe the clinical characteristics of persistent CHI and evaluate long-term neurological outcome and its risk factors in a cohort of Egyptian children. METHODS: Clinical, genetic, and biochemical data of 42 patients with CHI were collected. Patients were invited for neurological assessment, electroencephalogram, and magnetic resonance imaging of the brain. RESULTS: ABCC8 mutation was found in (61%) of cases who underwent genetic testing (17/28). Five cases with homozygous biparental ABCC8 mutation responded to combined diazoxide and octreotide without needing surgery. Seven out of twenty-one patients who had pancreatectomy (33%) developed diabetes after a median period of 4.8 (range:1-10) years following surgery. Fifty-five percent of our patients had neurodevelopmental impairment at follow-up. Logistic regression analysis has shown that delayed referral to tertiary centre for more than 8 days, delayed diagnosis of CHI for more than 14 days and hospital admission for more than 30 days, are significant predictors of unfavorable neurological sequelae in CHI; (OR = 12.7 [2.56], p = 0.001), (OR = 12.7 [2.9-56], p = 0.001), and (OR = 3.8 [0.14.5], p = 0.043), respectively. CONCLUSIONS: ABCC8 mutation was the commonest genetic mutation underlying CHI in this study group. CHI cases with biparental homozygous ABCC8 mutation may show response to combined octreotide and diazoxide therapy. More than half of our patients had neurodevelopmental impairment at follow-up. Delayed referral to expert centre, delayed diagnosis and longer hospital stay are significant predictors of neurological disability in CHI cases.

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.

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.

Left ventricular functions in pediatric patients with ten years or more type 1 diabetes mellitus: Conventional echocardiography, tissue Doppler, and two-dimensional speckle tracking study.

BACKGROUND: Cardiac dysfunction is a complication of type 1 diabetes mellitus (T1DM) with primary concern in adults. However, studies have evaluated left ventricle (LV) myocardial changes in pediatrics but not the long-term effect of T1DM in such vulnerable age. Therefore, we assessed LV functions in pediatric patients with long-duration T1DM using different echocardiographic modalities. METHODS: Between July 2015 and March 2016, 48 T1DM patients were prospectively compared to 35 healthy controls. Pediatric patients with T1DM for 10 years or more were included in the study. Patients were subjected to history taking, clinical examination, glycated hemoglobin (HbA1c), and microalbuminuria measurements. Moreover, conventional echocardiography, tissue Doppler, and 2D speckle tracking were performed to analyze LV functions. RESULTS: Mean age of patients was 15.5 ± 2 years, and mean T1DM duration was 11.7 ± 1.8 years. LV dimensions, EF and FS, and mass index did not statistically differ between groups, but E/E' ratio was significantly higher in the diabetic group. Global longitudinal strain (GLS) and global circumferential strain (GCS) were significantly lower in diabetic patients compared with controls (P = 0.038; P = 0.001, respectively). Mean HbA1c was found to be a significant predictor of decreased GLS in the diabetic population (95% CI, 0.096-0.244; P = 0.001) but not predicting GCS. Microalbuminuria had no significance in predicting strain. CONCLUSIONS: Despite the long-duration of affection with T1DM during childhood in our patients, alterations on LV myocardial function could not be detected either clinically or by conventional echocardiography. Tissue Doppler and speckle tracking could be used in the follow up of myocardial status in pediatric diabetic patients.

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.