Detection of prevalence of β-thalassemia trait in children attending a tertiary pediatric university hospital for non-hematological disorders using red blood cell indices

Background: The red cell indices have been reported to have a major role in detecting β-thalassemia carriers among children with hypochromic microcytic anemia, but still population studies show controversy on the choice of red cell indices and the cutoff values. Objective: The objective of this study was to detect the percentage of β-thalassemia carriers among children attending tertiary pediatric university hospital for non-hematological diseases and to test the sensitivity and specificity of different indices and formulas derived from automated hematology analyzer in detecting thalassemia carriers to determine the best index for screening in this age group. Materials and Methods: A cross-sectional study was conducted which included 200 children attending tertiary pediatric university hospital with non-hematological disorders for 6 months. Complete history was recorded for all children and complete blood picture was analyzed on Advia Sysmex analyzer, hemoglobin (hb) electrophoresis on Sebia Capillarys 2 instrument, and iron study in the form of serum iron and total iron-binding capacity. Gene mutation analysis for β-thalassemia was done by sequence-specific oligonucleotide hybridization for the common mutations for selected cases. Results: We detected a percentage of 7.5% β-thalassemia trait (TT) and 20% iron deficiency (ID) anemia among studied children. Hb distribution width is the parameter most useful in differentiating ID anemia and TT while Ehsani index was the best calculated index with the highest sensitivity and specificity. Conclusion: There is a lot of interpopulation difference in discriminative power of indices and cell parameters in differentiating ID and TT in children. We advocate larger studies in selected subpopulations to discriminate both diseases

Do vitamin d deficiency and hepatitis c virus infection play a role in oxidative stress in patients on maintenance hemodialysis?

Background: Elevated oxidant levels and low antioxidant levels in patients with end-stage renal disease (ESRD) play a significant role in the development of endothelial dysfunction, atherogenesis and cardiovascular disease (CVD). A deficiency in vitamin D (Vit.D) is also suggested to be responsible for the generation of oxidative stress (OS) and CVD. Among dialysis patients, conflicting data exist concerning the relationship between hepatitis C virus (HCV) infection and OS. We studied the relationship between 25Vit.D level, HCV infection, and plasma 8 iso-prostaglandin F2 α (8-ISO-PGF2α) as an OS marker in an Egyptian hemodialysis (HD) cohort.Methods: One hundred and twenty ESRD patients on HD were initially recruited to the study but only 88 patients have met the inclusion and none of the exclusion criteria. Midweek predialysis session blood samples were collected for the measurement of 25(OH) Vit.D, plasma 8-ISO-PGF2α, high sensitivity C – reactive protein (hs-CRP), and intact parathyroid hormone (intact PTH). Patients were stratified into two groups according to the presence or absence ofserum antibodies against HCV and their plasma 8-ISO-PGF2α were compared.Results: Vit.D deficiency was noted in 93% of the participants; the median 8-ISO-PGF2α level was 382 pg/mL. No significant correlation between Vit.D and 8-ISO-PGF2α levels was found. Thirty-two participants (36%) were HCV+ and their 8-ISO-PGF2α levels were significantly lower relative to in the seronegative group (median 171 vs. 647 pg/mL; P < 0.006).Conclusion: In this Egyptian HD cohort, Vit D deficiency was highly prevalent, yet failed to show any correlation with F2-isoprostanes. HCV+ HD patients might be shielded from OS

Characterization of abnormal sleep patterns in patients with obesity, type 2 diabetes, or combined

Introduction: Obesity and type 2 diabetes mellitus have reached epidemic proportions worldwide. Abnormal sleep has been linked to both incident and prevalent obesity and type 2 diabetes. We aimed to characterize abnormal sleep patterns [ASP’s] in patients with obesity, type 2 diabetes, or both.Subjects: The study included 92 subjects divided into four groups: Group 1, 23 obese patients (BMI > 30) with type 2 diabetes mellitus; Group 2, 23 non-obese diabetic patients; group 3, 23 obese subjects without diabetes; group 4, 23 matched healthy control subjects.Methods: Waist circumference and BMI [body mass index] estimation, fasting and post challenge plasma glucose ‘‘groups 2 & 4”, HOMAIR [Homeostatic model assessment- Insulin resistance] estimation, and finally evaluation for ASP’s using a CDC [Centers for Disease Control and prevention] validated questionnaire.Results: Post-prandial glucose and BMI significantly predicted Sleep latency and sleep hours at night respectively. Both group 1 and 3 compared to group 4 showed higher prevalence of: Insomnia [p < .01], snoring [p < .01], fragmented sleep [p < .05], excessive day time sleepiness [p < .001], and daytime dysfunction [p < .001]. Group 2 compared to group 4 showed higher prevalence of: Insomnia, snoring, fragmented sleep, and finally, daytime dysfunction [All p < .01]. Group 1 compared to groups 3 and 4 had significantly less hours of sleep at night [p < .01]. Group 1 compared to group 2 showed higher prevalence of: Insomnia, fragmented sleep, excessive day time sleepiness, and daytime dysfunction [All p < .05]. Finally, group 3 compared to group 2 showed higher prevalence of: Excessive day time sleepiness, and daytime dysfunction [p < .01].Conclusion: The combination of obesity and diabetes mellitus is associated with poor quality and quantity of sleep with resultant significant daytime dysfunction. Glycemic, and adiposity measures predicted sleep latency and hours.Keywords: Type 2 diabetes, Obesity, Abnormal sleep patterns, Insulin resistance Latency period, Impaired daily activitie

Management Of Bone Disease In Cystinosis: Statement From An International Conference

Cystinosis is an autosomal recessive storage disease due to impaired transport of cystine out of lysosomes. Since the accumulation of intracellular cystine affects all organs and tissues, the management of cystinosis requires a specialized multidisciplinary team consisting of pediatricians, nephrologists, nutritionists, ophthalmologists, endocrinologists, neurologists' geneticists, and orthopedic surgeons. Treatment with cysteamine can delay or prevent most clinical manifestations of cystinosis, except the renal Fanconi syndrome. Virtually all individuals with classical, nephropathic cystinosis suffer from cystinosis metabolic bone disease (CMBD), related to the renal Fanconi syndrome in infancy and progressive chronic kidney disease (CKD) later in life. Manifestations of CMBD include hypophosphatemic rickets in infancy, and renal osteodystrophy associated with CKD resulting in bone deformities, osteomalacia, osteoporosis, fractures, and short stature. Assessment of CMBD involves monitoring growth, leg deformities, blood levels of phosphate, electrolytes, bicarbonate, calcium, and alkaline phosphatase, periodically obtaining bone radiographs, determining levels of critical hormones and vitamins, such as thyroid hormone, parathyroid hormone, 25(OH) vitamin D, and testosterone in males, and surveillance for nonrenal complications of cystinosis such as myopathy. Treatment includes replacement of urinary losses, cystine depletion with oral cysteamine, vitamin D, hormone replacement, physical therapy, and corrective orthopedic surgery. The recommendations in this article came from an expert meeting on CMBD that took place in Salzburg, Austria, in December 2016.WoSScopu

Management of bone disease in cystinosis: Statement from an international conference

Cystinosis is an autosomal recessive storage disease due to impaired transport of cystine out of lysosomes. Since the accumulation of intracellular cystine affects all organs and tissues, the management of cystinosis requires a specialized multidisciplinary team consisting of pediatricians, nephrologists, nutritionists, ophthalmologists, endocrinologists, neurologists' geneticists, and orthopedic surgeons. Treatment with cysteamine can delay or prevent most clinical manifestations of cystinosis, except the renal Fanconi syndrome. Virtually all individuals with classical, nephropathic cystinosis suffer from cystinosis metabolic bone disease (CMBD), related to the renal Fanconi syndrome in infancy and progressive chronic kidney disease (CKD) later in life. Manifestations of CMBD include hypophosphatemic rickets in infancy, and renal osteodystrophy associated with CKD resulting in bone deformities, osteomalacia, osteoporosis, fractures, and short stature. Assessment of CMBD involves monitoring growth, leg deformities, blood levels of phosphate, electrolytes, bicarbonate, calcium, and alkaline phosphatase, periodically obtaining bone radiographs, determining levels of critical hormones and vitamins, such as thyroid hormone, parathyroid hormone, 25(OH) vitamin D, and testosterone in males, and surveillance for nonrenal complications of cystinosis such as myopathy. Treatment includes replacement of urinary losses, cystine depletion with oral cysteamine, vitamin D, hormone replacement, physical therapy, and corrective orthopedic surgery. The recommendations in this article came from an expert meeting on CMBD that took place in Salzburg, Austria, in December 2016.status: publishe

TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum

Ciliary dysfunction leads to a broad range of overlapping phenotypes, collectively termed ciliopathies. This grouping is underscored by genetic overlap, where causal genes can also contribute modifier alleles to clinically distinct disorders. Here we show that mutations in TTC21B, which encodes the retrograde intraflagellar transport protein IFT139, cause both isolated nephronophthisis and syndromic Jeune asphyxiating thoracic dystrophy. Moreover, although resequencing of TTC21B in a large, clinically diverse ciliopathy cohort and matched controls showed a similar frequency of rare changes, in vivo and in vitro evaluations showed a significant enrichment of pathogenic alleles in cases (P < 0.003), suggesting that TTC21B contributes pathogenic alleles to similar to 5% of ciliopathy cases. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of inherited disorders

TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum

Ciliary dysfunction leads to a broad range of overlapping phenotypes, termed collectively as ciliopathies. This grouping is underscored by genetic overlap, where causal genes can also contribute modifying alleles to clinically distinct disorders. Here we show that mutations in TTC21B/IFT139, encoding a retrograde intraflagellar transport (IFT) protein, cause both isolated nephronophthisis (NPHP) and syndromic Jeune Asphyxiating Thoracic Dystrophy (JATD). Moreover, although systematic medical resequencing of a large, clinically diverse ciliopathy cohort and matched controls showed a similar frequency of rare changes, in vivo and in vitro evaluations unmasked a significant enrichment of pathogenic alleles in cases, suggesting that TTC21B contributes pathogenic alleles to ∼5% of ciliopathy patients. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies, as well as interact in trans with other disease-causing genes, and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of disorders

Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment

No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate. Treatment with dexamethasone abolishes RhoA activation by knockdown of DLC1 or CDK20 indicating that steroid treatment in patients with pTSNS and mutations in these genes is mediated by this RLSG module. Furthermore, we discover ITSN1 and ITSN2 as podocytic guanine nucleotide exchange factors for Cdc42. We generate Itsn2-L knockout mice that recapitulate the mild NS phenotype. We, thus, define a functional network of RhoA regulation, thereby revealing potential therapeutic targets