Introduction X-linked hypophosphatemia (XLH) is a rare inherited cause of hypophosphatemic rickets and osteomalacia. It is caused by mutations in the phosphate-regulating endopeptidase homolog, X-linked (PHEX). This results in increased plasma fibroblast growth factor-23 (FGF23), which leads to loss of renal sodium-phosphate co-transporter expression leading to chronic renal phosphate excretion. It also leads to low serum 1,25-dihydroxyvitamin D (1,25(OH)2D), resulting in impaired intestinal phosphate absorption. Chronic hypophosphatemia in XLH leads to impaired endochondral mineralization of the growth plates of long bones with bony deformities. XLH in children and adolescents also causes impaired growth, myopathy, bone pain, and dental abscesses. XLH is the most frequent inherited cause of phosphopenic rickets/osteomalacia. Hypophosphatemia is also found in calcipenic rickets/osteomalacia as a result of secondary hyperparathyroidism. Thus, chronic hypophosphatemia is a common etiologic factor in all types of rickets. Results There is considerable overlap between symptoms and signs of phosphopenic and calcipenic rickets/osteomalacia. Wrong diagnosis leads to inappropriate treatment of rickets/osteomalacia. Nutritional rickets and osteomalacia are common in the Gulf Cooperation Council countries which include Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Bahrain, and Oman. Due to high levels of consanguinity in the region, genetic causes of phosphopenic and calcipenic rickets/osteomalacia are also common. Conclusion This guideline was developed to provide an approach to the diagnosis of XLH, especially where there is no family history of the disease, and that other related conditions are not mistaken for XLH. We also guide the medical management of XLH with conventional treatment and with burosumab, a recombinant human IgG1 monoclonal antibody to FGF23.

BACKGROUND: Screening for congenital hypothyroidism (CH) using cord blood or heel-stick samples is considered essential for the prevention of long-term complications CH, which include intellectual disability and slow growth.OBJECTIVE: Compare the sensitivity and specificity of cord blood and heel-stick samples for determining thyroid-stimulating hormone (TSH) levels for the detection of CH.DESIGN: Comparative diagnostic accuracy.SETTINGS: Tertiary care center in Riyadh.PATIENTS AND METHODS: The study included all infants who were delivered during the period from May 2011 to May 2013. As part of routine newborn screening, both cord blood and heel-stick samples were collected from each newborn for CH screening by measuring TSH levels. A cord TSH level was considered positive if the concentration of TSH was more than 60 mIU/L and negative if less than 30 mIU/L. Any cord TSH level between 30-60 mIU/L was considered borderline, and free T4 was measured from the same cord sample. The result was considered positive if the free T4 level was below 9 pmol/L. Heel-stick TSH levels more than 20 µU/L were considered positive. All newborns with positive results were recalled and a peripheral venous sample was taken for TSH and free T4 for confirmation.MAIN OUTCOME MEASURES: Sensitivity and specificity, positive and negative predictive values and recall rates.SAMPLE SIZE: 17 729 screened babies.RESULTS: Of 17 729 neonates screened, 7 were diagnosed as having primary CH. All confirmed cases were detected by both cord and heel-stick TSH levels: 88 cord results were positive (sensitivity 100%, specificity 99.6%, with a recall rate of 0.04%) and 305 heel-stick results were positive (sensitivity 100%, specificity 98.3%, with a recall rate of 1.68%).CONCLUSION: Both cord and heel-stick TSH testing detected all cases of CH. Cord testing was superior to heel-stick testing as the recall rate was lower. We think cord TSH testing is preferable when heel-stick is difficult or early discharge is the practice.LIMITATIONS: Retrospective; the timing of newborn screening for TSH sampling was premature.CONFLICT OF INTEREST: None.

X-linked hypophosphatemic rickets (XLHR) is a genetic disease caused by inactivating pathogenic variants in PHEX, which results in reduced mineralization of bone, teeth, and renal phosphate wasting. XLHR is traditionally treated by phosphate and vitamin D analogs. Recently, burosumab, a recombinant anti-fibroblast growth factor-23 (FGF-23) monoclonal antibody was approved as specific XLHR therapy. We aimed to assess the awareness, knowledge, and management of XLHR among members of the Arab Society for Pediatric Endocrinology and Diabetes (ASPED). Of the 97 physicians who answered the online questionnaire, 97% were aware of XLHR, and while 90% screen family members of the index case, only 29% manage children with XLHR. In children with rickets, 40% of participants measure serum/urine phosphate routinely, and 31% request serum FGF-23 in suspected XLHR cases. Almost all responders use conventional XLHR therapy, and 4% used Burosomab. Only 14% were satisfied with the conventional treatment, and 69% reported therapeutic complications in up to 25% of their patients. Multidisciplinary care for XLHR is practiced by 94%, but 82% of providers did not have transition clinics. Pediatric endocrinologists in ASPED countries are aware of XLHR but have variable practice and are unsatisfied with its conventional treatment. Raising awareness of the recognition and modern management of XLHR is needed.

Objectives: Diabetic-ketoacidosis (DKA) is a life-threatening complication and a leading cause of hospitalization in Type-1-diabetes (T1DM) patients. We aimed to assess the risk factors of admissions of children with DKA in a specialized children hospital in order to reduce morbidity and to inform appropriate prevention and intervention strategies. Methods: A retrospective review of all DKA admissions at King Abdullah Specialized Children’s Hospital, Riyadh (March 2015–December 2017). Data were gathered from newly diagnosed of T1DM and known patients ≤14-year-old with DKA criteria. The main variables were frequency, precipitating factors, and other characteristics of DKA admissions in both groups. Results: A total of 116/562 patients with T1DM (mean age 8.97±3.08 years) had 146 DKA episodes, of which 26/116 (34%) were newly diagnosed. The frequency of DKA admissions 2 were 146/562, 26%, of which (n=42/146, 28.7%) were newly diagnosed vs. (n=104/146, 71.2%) known patient of T1DM. The majority were 10-14 years (p≤0.001) and 55.5% were females. Missing insulin was the main precipitating cause of DKA (p=0.001) among known patients with T1DM. Recurrent episodes (n=30/164, 20.5%) occurred in 15/116 patients and were more common in children ≥10 years of age (P=0.024). The mean length-of-stay was 2.67±2.04 days and increased with DKA severity (P=0.008). Conclusions: In our study, the majority of DKA episodes were in patients with known T1DM; and missing insulin was the leading cause of DKA. In addition to awareness campaigns to prevent DKA as an initial presentation, intervention strategies should also target high risk groups of known patients of T1DM such as adolescents and patients with recurrent episodes.

Background: Vitamin D is a vital hormone in preserving calcium and phosphorus homeostasis in the body and maintaining normal growth and mineralization of bones. Case Presentation: We identified a patient with vitamin D dependent rickets type 1A (VDDR1A). This patient had rachitic skeletal manifestations, macrocephaly, retarded motor development, hypocalcemia, hypophosphatemia, markedly elevated alkaline phosphatase, and secondary hyperparathyroidism associated with normal 25 hydroxyvitamin D [25(OH)D] and low 1,25-dihydroxyvitamin D [1,25(OH)2D]. These biochemical abnormalities are consistent with the diagnosis of VDDR1A. Molecular analysis of CYP27B1 gene revealed novel homozygous mutation \"Gly125Arg\". Unaffected parents were heterozygous carriers. Conclusion: It is highly suggestive that \"Gly125Arg\" is the molecular defect causing this disease in our patient. Gly125Arg is likely to be a pathogenic mutation that leads to VDDR1A.

No abstract

Objective. Puberty has a significant contribution to the final height. Therefore, it is crucial to understand the normal variations in the onset and tempo of puberty in a specific population. In this study, we aimed to provide normative data on the timing of puberty and late pubertal height (LPH) in Saudi schoolboys in Riyadh. Methods. This is a cross-sectional field study (2011–2013) including Saudi schoolboys (grades 1–12; aged 6 to 19 years). Schools were chosen to represent the population from urban and rural areas in the Riyadh region. Pubertal maturity staging for gonads was assessed by measuring testicular size using a Prader orchidometer and assessing the Tanner staging of pubic hair. The marginal mean age was calculated using regression analysis. Results. We recruited 1086 schoolboys. The estimated mean age of pubertal onset at G2 was 11.8 (95% CI 11.60–12.0) years, for gonadal development at G3 was 13.2 (95% CI 12.9–13.5), G4 = 15.0 (95% CI 14.7–15.2), and G5 = 16.1 (95% CI 15.9–16.3) years, and for pubic hair stage 2 (PH2) was 12.6 (95% CI 12.4–12.9) years. The estimated time from G2/PH2 to G5/PH5 was 4.3 and 3.9 years, respectively. At the onset of puberty, the mean height was 144.7 cm and it reached 167.8 cm at G5 with a pubertal height gain of 23.1 cm. Conclusion. Our data present the norms of the timing of puberty and LPH in Saudi schoolboys. Saudi adolescent males are shorter than some European and American comparatives mainly due to shortness during childhood. However, they could have shorter LPH than Turkish, Greek, Thai, and Japanese due to a less pubertal height gain.

Background Goiter is a common presenting sign of various thyroid diseases in children. Thyroid nodules are clinically and/or radiologically significant findings due to their high malignancy rate. The ultrasound (US) characteristics of pediatric patients with goiter are rarely reported in literature; thus, the purpose of this study is to assess the characteristics of thyroid US and the prevalence of thyroid nodules in pediatric patients with goiter. Methods A retrospective review of children and adolescents under the age of 18 (2015–2020) referred for neck ultrasound due to goiter in clinical examination. Results A total of 262 patients were included with a mean age of 13.77 ± 3.7 years. Thyroid antibodies were positive in 119/262 (45.4%) patients. Thyroid US reported to be abnormal in 210/262 (80%) patients. Thyroid nodule were found in 33.6% (n = 88/262) of patients with goiter and in 41.9% (n = 88/210) of patients with abnormal thyroid US result. Patients with positive antibodies had more of heterogeneity and hypervascularity of the gland on thyroid US (P < 0.001). On the other hand, thyroid nodules were more likely to be presented in patients with negative thyroid antibodies (P = 0.025). The heterogeneity within the thyroid positive group was significantly correlated with increasing TPOAb (P < 0.001) and TSH levels (P < 0.028). Heterogeneity on US had a positive predictive value (P = 0.041), while hypervascularity had low prediction for thyroid nodules (P = 0.022). Age, gender, family history of thyroid diseases, antibodies status and echogenicity in US did not show any significant associations with thyroid nodules. Papillary thyroid carcinoma was diagnosed in six patients and one of these patients was positive for thyroid antibodies. Conclusion Thyroid nodules are quite common in our population. Thyroid nodules were significantly associated with heterogeneity in US. Although, no clinical or biochemical factors could predict the presence of thyroid nodules on thyroid US in our cohort, the absence of thyroid antibodies should lower the threshold for performing thyroid US.