Molecular Screening of PAX2 Gene Polymorphism in Primary Vesicoureteral Reflux Patients in Taif Governorate, KSA.

<b>Background and Objective:</b> Primary Nonsyndromic Vesicoureteral Reflux (PVUR) is a widespread genetic malformation and considered a prevalent Congenital Abnormality of the Kidney and Urinary Tract (CAKUT). Mutations in the <i>PAX2 </i>gene have been associated with abnormalities in the kidney extending from CAKUT to oncogenic processes. The present study analyzes the <i>PAX2</i> polymorphisms and their association with primary VUR in Saudi children patients from the Taif governorate. <b>Materials and Methods:</b> Fifteen children with primary VUR were identified and screened for gene mutations in the <i>PAX2</i> gene by direct sequencing method of purified Polymerase Chain Reaction (PCR) products of all exons to elucidate the correlation between <i>PAX2</i> gene and VUR. <b>Results:</b> Seven new variants have been defined. Three polymorphic missense variants in homozygous genotype form were found in intron 8 and detected in eight patients, One missense mutation was found in exon 10 in the site of transactivation domain and detected in ten patients and <i>in-silico</i> analysis predicted it as a pathogenic one, Three mutations were found in exon 11 and detected in all patients as a compound homozygous. <b>Conclusion:</b> <i>PAX2</i>is important for normal kidney development and mutations in the gene possibly lead to disturbance in the protein structure and could be non-functional thus mutations in <i>PAX2</i> may be one of the causes of PVUR in Saudi Arabia. Further investigation is necessary to understand the aetiology of disease and maybe other genes implicated in VUR.

Screening of SHOX gene sequence variants in Saudi Arabian children with idiopathic short stature.

PURPOSE: Short stature affects approximately 2%-3% of children, representing one of the most frequent disorders for which clinical attention is sought during childhood. Despite assumed genetic heterogeneity, mutations or deletions in the short stature homeobox-containing gene (SHOX) are frequently detected in subjects with short stature. Idiopathic short stature (ISS) refers to patients with short stature for various unknown reasons. The goal of this study was to screen all the exons of SHOX to identify related mutations. METHODS: We screened all the exons of SHOX for mutations analysis in 105 ISS children patients (57 girls and 48 boys) living in Taif governorate, KSA using a direct DNA sequencing method. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. RESULTS: A total of 30 of 105 ISS patients (28%) contained six polymorphic variants in exons 1, 2, 4, and 6. One mutation was found in the DNA domain binding region of exon 4. Three of these polymorphic variants were novel, while the others were reported previously. There were no significant differences in anthropometric measures in ISS patients with and without identifiable polymorphic variants in SHOX. CONCLUSION: In Saudi Arabia ISS patients, rather than SHOX, it is possible that new genes are involved in longitudinal growth. Additional molecular analysis is required to diagnose and understand the etiology of this disease.

Idiopathic hypoparathyroidism with extensive intracranial calcification in children: First report from Saudi Arabia.

RATIONALE: Pediatric idiopathic hypoparathyroidism with extensive intracranial calcifications outside the basal ganglia (BG) is extremely rare with less than 10 cases worldwide. PATIENT CONCERNS: An 11-year-old Saudi male child presented with tetany with otherwise normal neurological and other body system examination diagnoses severe hypocalcemia for differential diagnosis. INTERVENTIONS: Further investigations revealed hyperphosphatemia and undetectable serum intact parathyroid hormone. Brain computed tomography revealed BG and extensive brain calcifications. He has no dysmorphic features, vitiligo, mucocuataneous manifestations, or hair loss. He had normal hemoglobin, electroencephalogram, and skeletal survey, with negative autoantibodies to alpha and omega interferons and negative genetic testing for Glial Cell Missing 2 (GCM2) and calcium-sensing receptors (CaSRs) excluding known causes of hypoparathyroidism. OUTCOMES: This case presents a rare entity of idiopathic hypoparathyroidism with extensive intracranial calcification, not only in BG but also outside the extrapyramidal system with normal mentality, development, pubertal achievement, and neurological examination. To our knowledge, this is the first report from Saudi Arabia in pediatrics. LESSONS: Idiopathic hypoparathyroidism is a diagnosis of exclusion after ruling out all known causes of hypoparathyroidism. It is associated with BG calcifications, but extensive intracranial calcifications outside the BG are extremely rare.

Patterns of Childhood Steroid-Sensitive and Steroid-Resistant Nephrotic Syndrome in Saudi Children.

Nephrotic syndrome (NS) is one of the most common causes of chronic kidney disease in children. Mostly, NS is controlled by steroids. In spite of this, 10% to 20% of the patients have steroid resistant NS (SRNS), and the rest have steroid sensitive NS (SSNS). Eighty-seven children with NS (66 SSNS; 21SRNS) were retrospectively studied within the past 10 years in Taif region of Saudi Arabia. Regarding outcome, 66 (76%) patient responded to the steroid therapy, while 21 (24%) patients characterize as SRNS. Out of 66 SSNS, 25 children revealed complete remission, 26 were diagnosed as steroid dependent, and 15 were identified as frequent relapses. Among 21 SRNS biopsied patients, focal segmental glomerulosclerosis was the most common histological patterns of NS followed by the membranoproliferative glomerulonephritis pattern, which is significantly different from other studies performed in the Kingdom of Saudi Arabia. Out of 21 SRNS patients, 13 developed chronic kidney disease, 4 got end-stage renal disease, and 4 patients died.

A randomized clinical trial comparing 3 different replacement regimens of vitamin D in clinically asymptomatic pediatrics and adolescents with vitamin D insufficiency.

BACKGROUND: Pediatric and Adolescent populations both have special needs for vitamin D especially for growing bone. Inadequate vitamin D is defined as 25 (OH) D(25hydroxy vitamin D) < 30 ng/ml. METHODS: We conducted a randomized, controlled clinical trial from July 2014 over 1 year, aiming to assess the changes in 25 (OH) D and biochemical outcome on calcium and PTH(parathyroid hormone) using 3 different regimens of vitamin D replacement. Initial and 4 month 25 (OH) D, calcium, PTH and 12 month 25 (OH) D levels were assayed. Participants divided into 3 groups: 1) given 400 IU daily, 2) given 45000 IU weekly for 2 months then 400 IU daily, 3) given 2000 IU daily for 3 months then 1000 IU daily. RESULTS: The results showed significant difference between the 3 groups as regards 25 (OH) D at 4 and 12 months (P < 0.001). Regimens used in group 2 and 3 caused increase in 25 (OH) D after 4 month (median increase is 225% and 200% respectively). 25 (OH) D dropped in group 1 and 2 (median decrease is 42 and 53% respectively) but continued to increase in group 3 (median change is 6%). In group 2 serum calcium median change was 1.2% with few cases of hypercalcuria. 94.9, 76.1 and 7.7 are the percent of vitamin D deficient participants in groups 1, 2 and 3 respectively after 12 months follow up. CONCLUSION: We advise as a replacement for vitamin D insufficiency, low loading dose with high maintaince dose rather than the opposite to achieve steady increase in serum 25 (OH) D with no hypercalcemic side effects.

Peritonitis in children with automated peritoneal dialysis.

This is a retrospective study including 36 Saudi children who were on automated peritoneal dialysis (APD) at the Al-Hada Armed Forces Hospital, Taif, Kingdom of Saudi Arabia during seven years. A total of 10 boys and 26 girls with end-stage renal disease (ESRD) received APD for a total of 731.75 months. 36 episodes of peritonitis occurred in 17 children (47%). The frequency of peritonitis was one episode per 20.3 treatment months. Catheters were changed in 3 patients (8%). Three patients were switched to chronic hemodialysis, while 4 underwent successful renal transplantation. Results revealed that 11 patients (19%) were culturenegative, while 25 (81%) were culturepositive. Gram-positive organisms were responsible for the majority of peritonitis episodes (50%) followed by Gram-negative organisms (31%); occurrence was more frequent in young patients. Empiric antibiotic therapy covered both gram-positive and gram-negative organisms. However, all gram-positive isolated microorganisms showed sensitivity to vancomycin. On the other hand, most gram-negative organisms showed sensitivity to ceftazidime or tobramycin.

Cinacalcet in pediatric and adolescent chronic kidney disease: a single-center experience.

Cinacalcet, a calcimimetic drug, has been shown to be efficacious in adult chronic kidney disease (CKD) patients; however, it was not fully studied in pediatric CKD patients. We aimed at assessing the effect of cinacalcet on intact parathyroid hormone (iPTH) secretion in children with CKD-4/5 with iPTH consistently ≥ 300 pg/mL refractory to conventional treatment. This is a prospective cohort analysis of 28 children with uncontrolled hyper-parathyroidism secondary to stage 4 and 5 CKD admitted to a tertiary center during the period from April 2012 to April 2014. Twenty-eight patients with CKD-4/5 were assessed prospectively regarding bone biochemistry, renal ultrasonography, serum iPTH level, and medications. Patients were classified into 3 groups: group 1, 6 patients with CKD-4 on supplemental and supportive therapy; group 2, 6 patients with CKD-5 on hemodialysis and; group 3, 16 patients with CKD-5 on automated peritoneal dialysis. Patients were between the ages of 9 months and 18 years on commencing cinacalcet at doses of 0.5 to 1.5 mg/kg. All patients showed at least a 60% reduction in iPTH (60%-97%). Highly significant reduction in iPTH and serum alkaline phosphatase levels was detected post-cinacalcet. The serum calcium (Ca), phosphate (P), and Ca × P product were unaffected. Treatment was well tolerated with no hypophosphatemia, hypocalcemia, or other adverse effects almost in all patients. Cinacalcet use was proven safe for all pediatric and adolescent patients with CKD-4/5 during the study period, and at the same time most of the patients reached the suggested iPTH target values.

Screening for urine abnormalities among preschool children in western Saudi Arabia.

OBJECTIVES: To estimate the frequency of urinary problems among preschool children. METHODS: In this cross-sectional study, 1000 preschool asymptomatic children attending the outpatient clinics of the Children's Hospital, Taif, Kingdom of Saudi Arabia between August 2013 and December 2013 were subjected to dipstick urine analysis. Microscopic examination was performed for the abnormal dipstick samples, and children with hematuria were investigated for kidney function. RESULTS: Dipstick urine analysis revealed abnormal findings in 25.1% of the screened children. The most common dipstick abnormalities were positive nitrite test in 18.1%, hematuria in 16.9%, and positive leukocyte esterase test in 14.3% of the cases. The most common abnormality in microscopic urine examination was crystals in 13% of the cases. Pyuria were evident in 5% of cases and hematuria in 2.5%. The most common bacteria in positive urine culture samples was Escherichia coli in 62.6%. CONCLUSION: In view of these important findings, dipstick screening should be implemented in preschool children.