Prevalence of celiac-related antibodies and its impact on metabolic control in Egyptian children with type 1 diabetes mellitus.

OBJECTIVE: The simultaneous presence of celiac disease and type 1 diabetes (T1DM) is coupled with more hazards of comorbidities and complications. This current study aimed to screen for celiac disease in Egyptian children with type 1 diabetes and evaluate its impact on glycemic control. METHODS: A cross-sectional study was verified with 200 Egyptian children diagnosed with T1DM and having a diabetic duration of less than five years. Testing for anti-tissue transglutaminase IgA (tTG-IgA), anti-tissue transglutaminase IgG (tTG-IgG), anti-Endomysial IgA (EMA), and Hb A1c levels were done. RESULTS: The serological screening revealed that 11 cases (5.5%) tested positive; 8 children with T1DM (4.0%) showed tTG-IgA antibodies ≥ 10 times the upper limit of normal (ULN) with at least one symptom; and 3 cases (1.5%) had levels between 20 and 50 IU/ml (considering a cut-off point of 10 U/ML for positive results). Intestinal biopsy was performed for these three cases, with one case detected to have subtotal villous atrophy, resulting in an overall prevalence of celiac disease in T1DM as 4.5%. Children with positive screening exhibited a higher insulin dose, a higher HbA1c, an increased frequency of hypoglycemic attacks, and recurrent DKA compared to negative cases. A negative correlation was detected between tTG-IgA antibodies with height Z score and hemoglobin level, while a positive correlation was found between tTG-IgA antibodies and HbA1c level. CONCLUSION: Undiagnosed celiac disease in children with T1DM negatively impacted metabolic control and affected their general health.

Profile of plasma free amino acids, carnitine and acylcarnitines, and JAK2v617f mutation as potential metabolic markers in children with type 1 diabetic nephropathy.

Fifty diabetic nephropathy (DN) children with type 1 diabetes mellitus (T1DM) and 50 healthy matched controls were included. Chromatographic assays of 14 amino acids, free carnitine and 27 carnitine esters using high-performance liquid chromatography/electrospray ionization-mass spectroscopy, and genetic testing for JAK2v617f mutation using real-time PCR were performed. Patients had significantly lower levels of tyrosine, branched-chain amino acids (BCAAs), and BCAA/AAA (aromatic chain amino acids) ratios, glycine, arginine, ornithine, free carnitine and some carnitine esters (C5, 6, 12 and 16) and higher phenylalanine, phenylalanine/tyrosine ratio and C18 compared with the controls and in the macro-albuminuria vs. the microalbuminuria group (p < 0.05 for all) except for free carnitine. Plasma carnitine was negatively correlated with eGFR (r = -0.488, p = 0.000). There were significant positive correlations between tyrosine with UACR ratio (r = 0.296, p = 0.037). The plasma BCAA/AAA ratio showed significant negative correlations with UACR (r = -0.484, p = 0.000). There was a significantly higher frequency of the JAK2V617F gene mutation in diabetic nephropathy patients compared with the control group and in macro-albuminuria than the microalbuminuria group (p = 0.000) for both. When monitoring children with T1DM, plasma free amino acids and acylcarnitine profiles should be considered, especially if they have tested positive for JAK2V617F for the early diagnosis of DN.

Metabolic Analysis of Methylenetetrahydrofolate Reductase Single Nucleotide Polymorphisms (MTHFR 677C

Neural tube defects (NTDs) are among the most prevalent and debilitating birth defects with their causes are still unknown, despite mounting evidence that genetic and/or environmental factors may play a role. We aimed to analyze two single nucleotide polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene, serum folate and vitamin B12 status among a cohort of Egyptian children with NTDs and their mothers. A case-control study has been conducted on 50 Egyptian children with various types of NTDs and their mothers. They were comparable with 50 unrelated healthy, age and sex matched children and their mothers (50) selected as controls. Pediatric and neurosurgical assessments were performed to the included cases. Serum folate and vitamin B12 were measured using ELISA kits. MTHFR 677C

Lactate and intestinal fatty acid binding protein as essential biomarkers in neonates with necrotizing enterocolitis: ultrasonographic and surgical considerations.

BACKGROUND: Necrotizing enterocolitis (NEC) is a neonatal disease with its pathogenesis still not well understood, although it is hypothesized to be related to decreased perfusion of the intestinal wall. The current study aimed to evaluate the plasma lactate levels and assess the validity of plasma and urinary intestinal fatty acid binding protein (I-FABPp and I-FABPu/Cru respectively) in NEC. METHODS: The study included 55 neonates with variable Bell's stages who were comparable with 23 matched controls. Colorimetric assays of plasma lactate and ELISA assays of I-FABP in both serum and urine of the included neonates have been performed. RESULTS: There were significantly higher median levels of I-FABPp, I-FABPu and lactate among cases (2.84 ng/ml, 1.74 ng/g creat. and 32.34 mg/dl, respectively) compared with controls (0.16 ng/ml, 0.60 ng/g creat. and 15.33 mg/dl, respectively) with p ˂ 0.05 for all. I-FABPp at cut-off point >3.24 ng/ml showed 90% sensitivity, 72% specificity, PPV = 52.6%, NPP = 94.7%, while for I-FABPu (at cut-off point > 2.93 ng/g creat.) those values were 90%, 92%, 81.8% and 95.8% respectively, in discriminating stage IIIA from stage II with p = 0.001. In predicting surgical NEC, I-FABPp at the cut-off point of 6.95 ng/ml revealed 75% sensitivity, 100% specificity, PPV = 100%, NPP = 95%, while for I-FABPu (cut-off point>4.13 ng/g creat.) they were 100%, 76.19%, 44.4 %and 100%, p = 0.04. CONCLUSION: s: In addition to clinical judgment, sonographic data and plasma lactate, I-FABPp was shown to be a specific marker for early identification of surgical NEC, while I-FABPu could be more useful for differentiating Bell's stage II from stage III.

Assessments of Amino Acids, Ammonia and Oxidative Stress Among Cohort of Egyptian Autistic Children: Correlations with Electroencephalogram and Disease Severity.

OBJECTIVE: The current study aimed to assess the profiles of plasma amino acids, serum ammonia and oxidative stress status among autistic children in terms of electroencephalogram findings and clinical severity among the cohort of autistic Egyptian children. PATIENTS AND METHODS: The present study included 118 Egyptian children categorized into 54 children with autism who were comparable with 64 healthy controls. Clinical assessments of cases were performed using CARS in addition to EEG records. Plasma amino acids were measured using high-performance liquid chromatography (HPLC), while, serum ammonia and oxidative stress markers were measured using colorimetric methods for all included children. RESULTS: The overall results revealed that 37.04% of cases had abnormal EEG findings. Amino acid profile in autistic children showed statistically significant lower levels of aspartic acid, glycine, ß-alanine, tryptophan, lysine and proline amino acids with significantly higher asparagine amino acid derivative levels among autistic patients versus the control group (p˂0.05). There were significantly higher serum ammonia levels with significantly higher total oxidant status (TOS) and oxidative stress index (OSI) values among the included autistic children vs controls (p˂0.05). There were significantly negative correlations between CARS with aspartic acid (r=-0.269, P=0.049), arginine (r= - 0.286, p= 0.036), and TAS (r= -0.341, p= 0.012), and significantly positive correlations between CARS with TOS (r=0.360, p= 0.007) and OSI (r= 0.338, p= 0.013). CONCLUSION: Dysregulated amino acid metabolism, high ammonia and oxidative stress were prevalent among autistic children and should be considered in autism management. Still EEG records were inconclusive among autistic children, although may be helpful in assessment autism severity.

Possible Associations of Disturbed Neurometals and Ammonia with Glycaemic Control in Type 1 Diabetic Children with Attention Deficit Hyperactivity Disorder.

The chronicity of type 1 diabetes mellitus (T1DM) is reported to be associated with various psychological disorders. The current study aimed to evaluate the levels of serum ammonia and various neurometals (zinc, copper, and magnesium) in patients with T1DM with and without ADHD and to correlate their levels with glycaemic status. A prospective case-control study was conducted with 60 diabetic children with T1DM (allocated into a group of 20 patients with a diagnosis of ADHD and a group of 40 patients without ADHD) who were comparable to 60 matched controls. Assays of glucose, glycated haemoglobin (HbA1c), ammonia, zinc, copper, and magnesium were performed. Overall, ammonia and copper levels were significantly higher in the diabetic patients especially those with ADHD than in the control group (p Ë‚ 0.05 for all). The calculated copper/zinc ratio was significantly higher in the diabetic patient group than in the control group and higher in diabetic children with ADHD than in diabetic children without ADHD (p Ë‚ 0.05 for all). Diabetic children had significantly lower magnesium levels than the controls (p Ë‚ 0.05), but no significant difference between the diabetic subgroups was detected. A positive correlation between glycaemic control (HbA1c %) and ammonia level was found in the diabetic group and subgroups, and a positive correlation was found between HbA1c % and the Cu/Zn ratio in diabetic children with ADHD (p Ë‚ 0.05 for all). The current study confirms an association of elevated ammonia and copper/zinc ratio with poor glycaemic control and ADHD development among children with T1DM.

Vitamin D receptor rs7975232, rs731236 and rs1544410 single nucleotide polymorphisms, and 25-hydroxyvitamin D levels in Egyptian children with type 1 diabetes mellitus: effect of vitamin D co-therapy.

Purpose: We aimed to examine the possible association role of vitamin D and vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) in type 1 diabetes mellitus (T1DM) development, glycemic control and complications among a cohort of Egyptian children. Subjects and methods: A prospective case-control study has been conducted on 50 Egyptian children with T1DM who were comparable with 50 controls. Vitamin D and HbA1c were measured. VDR-SNPs [ApaI (rs7975232), TaqI (rs731236) and BsmI (rs1544410)] detection was done by polymerase chain reaction through restriction fragment length polymorphism (PCR-RFLP) technique. Vitamin D supplements were given to the included T1DM children with low vitamin D and reassessments of both HbA1c% and 25(OH)D serum levels were performed in those children three months later. Results: Eighty percent of the included diabetic patients have poor glycemic control. Vitamin D was deficient in 68% and insufficient in 16% of diabetic patients. Significant improvements in both vitamin D and glycemic status among T1DM children, who have low vitamin D and received vitamin D supplementations. There were significantly negative correlations between serum levels of vitamin D with both HbA1c % (r= -0.358, P˂0.05) and daily insulin dose (r=-0.473, P˂0.05). Compared with controls, T1DM children presented more commonly with ApaI a allele (OR: 2.87; 95%CI: 1.39-5.91, P˂0.05) and BsmI b allele (OR: 4.38; 95%CI: 2.30-8.33, P˂0.05). TaqI t allele wasn't significantly differing among patients and controls (P˃0.05). Aa+aa and Bb+bb genotypes were significantly higher among T1DM vs the controls (OR: 3.08;, 95%CI: 1.33-7.15, P˂0.05 and OR: 9.33; 95%CI: 3.61-24.17, P˂0.05respectively). Conclusion: ApaI and BsmI were associated with risk of T1DM development among Egyptian children. Low vitamin D status was frequently occurring among T1DM with significant improvement in the glycemic control of such children when adding vitamin D supplements to the standard insulin therapy.

Possible Metabolic Alterations among Autistic Male Children: Clinical and Biochemical Approaches.

The present cross-sectional, hospital-based study was carried out on 146 Egyptian male children, 73 males with autism who were comparable with another 73 healthy age- and sex-matched children, recruited from the outpatients' psychiatric clinics of the Neuropsychiatric and Pediatric Departments of South Valley and Assiut University Hospitals, Egypt. Neuropsychological assessments of autistic males were done using CARS, short sensory profile and intelligent quotients. Serum markers of mitochondrial dysfunction (lactate, pyruvate, and lactate to pyruvate ratio, creatine kinase (CK), L-carnitine, ammonia, lactate dehydrogenase, pyruvate kinase, alanine transaminase and aspartate transaminase), oxidative stress and blood levels of heavy metals (mercury, lead and aluminium) were measured. Serum cholesterol, cortisol, free testosterone, estradiol, dehydroepiandrostenedione, adenosine deaminase and Helicobacter pylori antigen in stool were also performed. There was evidence of mitochondrial dysfunction among autistic children. Additionally, there were significantly lower serum total cholesterol, cortisol and estradiol as well as significantly higher dehydroepiandrostenedione (DHEA) and free testosterone (p < 0.05 for all markers). Twenty-eight (38%) cases were positive for H. pylori antigen in their stool with significant higher serum ammonia and lower adenosine deaminase than in H. pylori-negative autistic children. Mitochondrial dysfunction, H. pylori infection and low cholesterol were prevalent among autistic male children, which should be targeted during autism management.

Biochemical assessments of thyroid profile, serum 25-hydroxycholecalciferol and cluster of differentiation 5 expression levels among children with autism.

BACKGROUND: The exact pathogenesis of autism is still unknown. Both thyroid hormones and 25(OH)D are important for brain development, in addition to CD5; all have immunomodulatory actions by which their dysregulation may have a potential role in autism pathogenesis. OBJECTIVES: The objectives of this study were to assess the thyroid profile, serum 25(OH)D levels and CD5 expression levels among autistic patients and to find out the correlations between the measured biomarkers with each other on one side and with the disease severity on the other side. PATIENTS AND METHODS: This cross-sectional case-control study has been conducted on 60 children with autism and 40 controls, recruited from Qena Governorate, Upper Egypt. Childhood Autism Rating Scale (CARS) score was used to assess the included patients. Biochemical assays of thyroid function in the form of free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroid-stimulating hormone (TSH) and 25(OH)D were done using commercially available enzyme-linked immunosorbent assay (ELISA) kits, while CD5 expression levels were measured using flow cytometry (FCM) analysis for all the included patients and controls. RESULTS: The overall measurement results show significant higher mean serum TSH levels, mean CD5 expression levels with significant lower mean serum 25(OH)D levels among autistic children when compared with the control group (p<0.05 for all). Significant negative correlations between CD5 with FT3, FT4 and 25(OH)D were observed. CARS score showed significant negative correlations with both FT3 and 25(OH)D, while it was positively correlated with CD5 in a significant manner (p<0.05 for all). CONCLUSION: Elevated CD5 expression and decreased 25(OH)D stores could play a potential role in the pathogenesis of autism via their immune-modulator actions. High TSH serum levels among autistic children, although within the physiological range, reflect the presence of thyroid dysfunction among such children, which needs further assessment.