Vitamin D and left ventricular dysfunction in pediatric dialysis patients; a tissue doppler study.

BACKGROUND: Assessment of the left ventricular function in the dialysis children and explore its association with vitamin D level and markers reflecting calcium and phosphate metabolism. METHODS: In this case-control study, we enrolled forty children on regular hemodialysis and forty healthy controls from July 2019 to March 2020 at the pediatric dialysis unit. Echocardiographic evaluation using both conventional and Tissue Doppler Imaging (TDI) was done for all subjects. Vitamin D and its markers were analyzed to assess its association with ventricular dysfunction. RESULTS: Diastolic function in children on hemodialysis was significantly impaired as evidenced by lower Mitral E/A velocity ratio (E/A), lower early diastolic velocity (E'), and higher E/E' ratio (Ratio of early diastolic mitral inflow velocity (measured by pulsed wave traditional Doppler) to early diastolic mitral annular velocity (measured by Tissue Doppler). in comparison with the controls. Most end stage renal disease (ESRD) participants had vitamin D deficiency. There was an important correlation between left ventricular (LV) dysfunction and both Vitamin D deficiency and hyperparathyroidism. Although our patients had normal systolic function by conventional and Tissue Doppler echocardiographic study, mean values of TDI- MPI (Mean Performance Index) in the haemodialysis group were significantly higher than in the control group, which indicates impaired global cardiac systolic and diastolic function. CONCLUSIONS: Tissue Doppler Imaging (TDI) provides a good reflection of the LV diastolic function. As vitamin D deficiency has been substantially associated with worsening of LV dysfunction, we suggest that TDI and Vitamin D might be included in the routine follow-up of pediatric dialysis patients.

Impact of genotype on endocrinal complications in ß-thalassemia patients.

In ß-thalassemia, certain mutations cause a complete absence of ß-globin chain synthesis, termed ß0-thalassemia, while others may allow certain ß-globin production and are termed ß+- or ß++-thalassemia. The homozygous state results in severe anemia, which requires regular blood transfusion. By contrast, frequent blood transfusion can in turn lead to iron overload, which may result in several endocrinal complications. The present study aimed to investigate the impact of genotype on the development of endocrine complications in ß-thalassemia patients. A cross-sectional study was conducted on 100 thalassemia patients >10 years. A data abstraction form was designed to capture the appropriate information from the individual medical records, including full clinical, laboratory, transfusion and chelation data. The genotype of the patients was identified by the DNA sequencing technique. Growth retardation and hypogonadism were the most prominent endocrinal complications (70 and 67%, respectively) followed by hypothyroidism, diabetes mellitus and hypoparathyrodism (8, 8 and 7%, respectively). The most common mutations identified were IVS-1-110, IVS-1-1 and IVS-1-6 (63, 47 and 41%, respectively). Patients with the ß0ß0 genotype had a significantly higher prevalence of growth retardation, hypogonadism, hypothyroidism and hypoparathyrodism compared to those with the ß0ß+ and ß+ß+ genotypes (P<0.001, P<0.001, P<0.001 and P=0.037, respectively). Patients with the homozygous IVS-11-745 mutation had a significantly higher prevalence of diabetes (P=0.001). The underlying genetic defect in thalassemia patients is a contributing factor for the development of endocrinal complications, as patients with the more severe defects have a greater rate of iron loading through higher red cell consumption.

The association of PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms with T1D in Egyptian children.

BACKGROUND: Type 1 diabetes mellitus (T1D) is a T cell-mediated autoimmune disease characterized by the destruction of pancreatic ß cells. PTPN22 and IL2RA polymorphisms have been found to be associated with several autoimmune diseases including T1D. AIMS: We aimed to elucidate the role of PTPN22 and IL2RA polymorphisms in predisposition of T1D in Egyptian children. METHODS: We studied 150 children and adolescents with T1D and 165 healthy controls. The PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms were genotyped using polymerase chain reaction. RESULTS: We found that carriers of the T allele of PTPN22 were significantly more likely to develop T1D (OR=2.2, 95% CI=1.2-4, P=0.01). Also, the carrier of TT genotype and T allele of IL2RA more likely to develop T1D (OR=2.8, 1.4, respectively, P=0.03). There was a statistically significant association between T allele of PTPN22 gene and females ⩽10years old at the onset of diabetes (OR=4, 95% CI=1.2-13.4, P=0.019). CONCLUSION: This study suggests a possible association between the T allele of PTPN22 gene and TT genotype of IL2RA with T1D in studied Egyptian children, especially, females with early onset diabetes who carried the 1858T allele.

ADAM33 and ADAM12 genetic polymorphisms and their expression in Egyptian children with asthma.

BACKGROUND: The ADAM family is involved in some pathologic processes, such as inflammation and asthma. OBJECTIVES: To assess the association between ADAM33 and ADAM12 single-nucleotide polymorphisms (SNPs) with asthma risk and severity and to investigate the effect of ADAM33 and ADAM12 polymorphisms on expression of these proteases in sputum. METHODS: Two SNPs of the ADAM33 gene, F+1 (rs511898) G/A and ST+4 (rs44707) A/C, and 2 SNPs of the ADAM12 gene, rs3740199 and rs1871054, were analyzed in 400 asthma cases and 200 controls aged 3 to 14 years using the polymerase chain reaction-restriction fragment length polymorphism method. Messenger RNA expression profile of ADAM33 and ADAM12 proteases in sputum from studied groups was determined by reverse transcription polymerase chain reaction. RESULTS: ADAM33 F+1 homozygous mutant genotype (AA) and ST+4 heterozygous and homozygous mutant genotype (AC and CC) and mutant alleles of both polymorphisms were significantly associated with asthma risk and severity in moderate and severe subgroups. Patients with the ADAM12 (rs3740199) CC genotype were at increased risk for moderate and severe asthma. Messenger RNA levels of ADAM12 were significantly increased in asthmatic children compared with controls, whereas we were not able to detect the expression of ADAM33 in the sputum of the groups studied. The ADAM12 expression was significantly higher in homozygous CC (variant type) compared with homozygous GG (wild type) of both ADAM12 rs3740199 and rs1871054 in the asthmatic group. CONCLUSION: Our analysis suggests a likely role for ADAM33 and ADAM12 in the development of asthma in Egyptian children. Furthermore, ADAM12 polymorphisms may affect ADAM12 expression in asthma.

First report of acute lymphoblastic leukemia in an Egyptian child with ß-thalassemia major.

ß-Thalassemia (ß-thal) is the most common hereditary anemia in humans. With improvement of treatment protocols, patients are living longer and new complications have emerged. Few articles have reported the occurrence of malignancies among patients with ß-thal in different parts of the world. We herein report the first pediatric patient with ß-thal major (ß-TM), who developed acute lymphoblastic leukemia in Egypt with analysis of the different theories of pathogenesis.

Association of 5-HT2A receptor gene polymorphisms with gastrointestinal disorders in Egyptian children with autistic disorder.

Gastrointestinal disturbances (GID) are frequently reported in children with autism spectrum disorders (ASD). Recently, mounting evidence suggests that there may be a genetic link for autism with gastrointestinal disturbances. We aimed to investigate whether there were any association between the -1438A/G, 102T/C and His452Tyr polymorphisms of the serotonin 2A receptor gene (5-HT2A) in Egyptian children with ASD and GID. Eighty children with autistic disorder and 100 healthy control children were examined. -1438A/G, 102T/C and His452Tyr polymorphisms of 5-HT2A were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Significant increase of the G allele and the GG genotype of the -1438A/G polymorphism was observed in children with autism than control, but there were no significant differences in the frequencies either of the 102T/C genotype or His452Tyr genotype between the two groups. There was a significant increase of homozygote A allele of the -1438A/G and CC genotype of the 102T/C polymorphism in ASD children with GID. This study supports the possible involvement of the 5-HT2A receptor in the development of ASD and associated GID.

Catechol-O-methyltransferase Val158Met polymorphism and hyperactivity symptoms in Egyptian children with autism spectrum disorder.

Catechol-O-methyltransferase (COMT) plays an important role in the catabolism of brain dopamine and norepinephrine, which have been implicated in the pathogenesis of Autism spectrum disorder (ASD) as well as in other neuropsychatric disorders. We aimed to investigate the association of COMT Val158Met gene polymorphism with ASD and to examine the influence of such genotypes on hyperactivity symptoms in ASD patients. Eighty ASD patients (mean age 9 ± 1.9 years) and 100 control children (mean age 8.9 ± 1.9 years) were examined. COMT Val58Met polymorphism was genotyped using Tetra-primer ARMS-PCR method. The clinical diagnosis of ASD and ADHD were confirmed according to the DSM-IV criteria for research. We found no significant difference in genotypes or alleles' frequencies of COMT Val158Met polymorphism between ASD patients and control group. There was a significant association between COMT (Val/Val) genotype and both increasing CARS (p=0.001) and hyperactivity scores (p=0.006). Regarding Conner's Score, the DSM-IV hyperactive impulsive were significantly higher in Val/Val genotype than both Met/Val and Met/Met genotypes (p=0.03). Our data suggested an association between COMT Val58Met polymorphism and hyperactivity symptoms in Egyptian children with ASD.