Abdulla A. Alharthi

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.

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.

Screening for urine abnormalities among preschool children in Western Saudi Arabia

I read with interest a study by Alharthi et al1 on the screening for urine abnormalities among preschool children in western Saudi Arabia. The authors stated that dipstick urine analysis (DUA) 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%. In view of the aforementioned data, the authors recommended implementing DUA screening among preschool children. Unexpectedly, the authors did not consider limitations in their study before making that recommendation. Hence, I presume that their recommendation ought to be cautiously considered owing to the presence of the following 4 limitations: 1) The study period was relatively short (August-December); 2) The data were obtained from a single center. It is, therefore, not truly representative of the whole pediatric population in the Kingdom of Saudi Arabia (KSA); 3) Generally, the magnitude of a certain health problem in a given population ought to be sizable in order to merit screening. The reported incidence of pediatric chronic kidney diseases (CKDs) was recently reported to be <1.0-8, and end-stage renal diseases (ESRDs) in the developing countries had been 3.4-35 per million child population.2 However, the exact magnitude of pediatric CKDs in KSA is not yet known as there is no current national epidemiologic data on that issue;3 and 4) The cost-effectiveness ratio of DUA for the early detection of CKDs needs to be considered. In an interesting American study,4 decision analysis was used to model a screening DUA strategy relative to a no-screening strategy. The expected costs and effectiveness for the no-screening strategy were 0 dollars as no resources were used, and no cases of CKDs were diagnosed. However, the screening strategy involved a cost of 3.05 dollars per dipstick. Accounting for true-positive and false-positive initial screens, 14.2% of patients required a second dipstick as per typical clinical care, bringing the expected cost of the screening strategy to 3.47 dollars per patient. In the screening strategy, one case of CKD was diagnosed per 800 screened, and the incremental cost-effectiveness ratio was 2,779.50 dollars per case diagnosed.4 In brief, I presume that conducting large scale multicenter studies over an extended period of time to assess the yield of DUA in early detecting urine abnormalities together with the determination of cost-benefit ratio for Saudi pediatric population are essential prerequisites to justify the implementation of DUA screening program.