Afaf Alsagheir

Achondroplasia (ACH) results from a missense mutation in the FGFR3 (fibroblast growth factor receptor 3) gene, representing the primary cause of short stat

Purpose: This research aims to investigate the medical, socioeconomic, and cultural factors influencing the quality of life (QoL) in parents of children with cystic fibrosis (CF), congenital adrenal hyperplasia (CAH), and Duchenne muscular dystrophy (DMD). Methods: This cross-sectional single-centered study included parents of children diagnosed with CF, CAH, or DMD at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. The QoL was assessed using the PedsQL™ Family Impact Module. Results: A total of 107 parents participated (response rate: 77%), including CF ( n = 40), CAH ( n = 26), and DMD ( n = 41). Fathers comprised 59.8% of respondents. 85% of fathers were employed compared to 15% in mothers. Consanguinity was reported in 77.6% of families. Diagnostic delays exceeding 1 year occurred in 46.7% of cases, particularly in DMD (82.9%). Only 10.3% of parents participated in support groups. Multi-variate analysis using a generalized linear model showed that frequent emergency department visits (>6 per year) and DMD diagnosis were predictors of lower QoL ( p = 0.003) and ( p = 0.004), respectively. Higher QoL was associated with maternal status ( p = 0.045) and higher income ( p = 0.014). Conclusion: Overall, the study found that parents of children with rare diseases experience a suboptimal QoL score, with parents of children with DMD faced the greatest challenges, suggesting targeted interventions like enhanced newborn screening and utilizing genetic testing for expedited diagnosis may be beneficial. The study also found that frequent emergency department visits negatively impacted QoL, suggesting that enhancing healthcare access through medical education, and the integration of telemedicine and home healthcare services might alleviate the burden faced by caregivers. Moreover, financial support to these families might play a role in enhancing their quality of life due to high prevalence of sole providers, and caregiver saturation. The low participation in support groups signals a gap in caregiver support that requires further exploration.

Background: Congenital adrenal hyperplasia (CAH) treatment is complicated by hormonal imbalances, necessitating a dual therapeutic approach to both correct cortisol deficiency and manage androgen overproduction. Unfortunately, hospitals with limited resources lack some necessary standard laboratory tests to manage patients with CAH. Objective: To investigate the interrelation between different monitoring strategies in clinical practice for managing patients with CAH. Methods: This prospective cross-sectional study involved children with CAH caused by 21-hydroxylase deficiency (21-OHD) treated at King Faisal Specialist Hospital and Research Centre. KFSHRC is not resource-limited; the proposed recommendations are intended for settings that lack full biochemical panels. Univariable, bivariable, and multivariable logistic regression were done for association testing. Results: The cohort included 96 children with 21-OHD, predominantly female (61.5%), with a median age of 6 years. Adrenal crises occurred in 20.8% of patients. Most participants were treated with hydrocortisone (97.9%) and fludrocortisone (88.5%), with high reported treatment compliance (90.6%). Biochemical abnormalities were observed in 26% for ACTH, 21.9% for 17-OHP, and 17.7% for testosterone. Biochemical control was significantly associated with treatment compliance (OR 7.6, p = 0.03). In adjusted analyses, androstenedione, ACTH, and testosterone control were strongly associated with 17-OHP control (all p < 0.01). Regarding skeletal outcomes, older age was inversely associated with bone age control, whereas clinical control (OR 11.1, p < 0.01) and controlled androstenedione levels (OR 3.0, p = 0.04) were independent predictors of optimal bone age. Conclusion: Based on these findings, we recommend integrating growth velocity monitoring and androstenedione testing into routine visits as valuable indicators for assessing clinical control in 21-OHD children. Yet, larger studies are needed to validate simplified monitoring frameworks for resource-limited hospitals.

Introduction: Hypophosphatasia (HPP) is a rare inherited metabolic disease caused by mutations in the ALPL gene. The disease is heterogeneous, complicating its diagnosis and delaying optimal management, leading to severe or lethal outcomes such as failure to thrive, fragility fractures, bone deformities, delayed motor development, respiratory failure, seizures, and premature death. However, no epidemiological studies on the incidence of HPP in Saudi Arabia have been identified until now. Therefore, the study aimed to describe the phenotype and genotype of Saudi patients with HPP. Methods: This retrospective multicenter case series included six centers in Saudi Arabia. Paediatrics and adult patients with clinically and genetically confirmed HPP were included between January 2014 and May 2024. Demographic and clinical information, including medical history, clinical, biochemical, genetic, and management data, was collected retrospectively from medical records and summarized descriptively. Additionally, whole-exome sequencing or ALPL next-generation sequencing (NGS) was performed. Furthermore, pre- and post-analysis for patients who received asfotase alfa was performed using the Wilcoxon signed-rank test. Results: The study included 19 HPP cases, of whom 68.4% were male. There were five patients with perinatal onset (26.3%), 13 with infantile onset (68.4%), and one with childhood onset (5.3%) of HPP. About 78.9% of patients indicated a family history of HPP; consanguinity was observed in nearly all parents of cases. Bone deformities were observed in all patients, including skull (78.5%), limb (100%), spinal (49.9%), and dental abnormalities (57.9%). Complications such as craniosynostosis (78.5%), nephrocalcinosis (26.3%), kyphoscoliosis (49.9%), and convulsions (26.3%) were also documented, with 4 (21.05%) deaths. Thirteen (68.4%) of our patients received asfotase alfa. All cases tested positive for ALPL variants, with the most common being c.293C>T (p.Ser98Phe) and c.977G>T (p.Gly326Val), both of which were novel and not previously reported. Conclusion: Our study highlights HPP’s diverse phenotypes and genotypes in Saudi Arabia, revealing distinct ALPL mutations. We identified a high prevalence of consanguinity and family histories of HPP. Treatment with asfotase alfa was generally effective and safe.

Objectives: Steroidogenic acute regulatory (StAR) protein deficiency is a rare autosomal recessive disorder that disrupts steroid hormone biosynthesis, resulting in congenital adrenal hyperplasia (CAH) and variations in sexual development. However, limited data is available in Saudi Arabia. Therefore, this study describes the clinical and genetic findings of seven Saudi patients with StAR deficiency. Methods: This case series was conducted at King Faisal Specialist Hospital and Research Centre (KFSHRC) in Riyadh, Saudi Arabia. Results: All seven patients were born to consanguineous parents, most commonly first cousins. Five patients had a 46,XY karyotype, and two had a 46,XX karyotype. All were clinically diagnosed with CAH due to StAR deficiency. Despite their chromosomal sex, all presented with a female external phenotype. Clinical features ranged from typical female genitalia to varying degrees of feminization with bilateral inguinal gonads or undescended testes in 46,XY individuals. Most patients exhibited electrolyte disturbances and chronic salt‐wasting. Interestingly, two cases presented with neonatal cholestatic jaundice. Genetic testing confirmed homozygous pathogenic or likely pathogenic STAR variants in all cases. Dysmorphism occurred in one patient with (c.402T >G, p.Tyr134Ter) mutation. The five 46,XY patients underwent bilateral gonadectomy. All patients remain clinically stable on long‐term steroid replacement. Conclusion: This study highlights the diverse clinical spectrum of StAR deficiency, ranging from early adrenal crisis to DSD and atypical presentations such as cholestasis. The findings underscore the importance of early genetic diagnosis and counseling, particularly in consanguineous populations, and point to the need for continued research into the clinical and molecular complexity of StAR deficiency.

Background: Denys‐Drash syndrome (DDS) is a rare genetic disorder characterized by mutations in the Wilms tumor suppressor gene ( WT1 ), leading to a triad of conditions including nephrotic syndrome progressing to end‐stage renal disease (ESRD), Wilms tumor, and ambiguous genitalia. We present two pediatric cases illustrating the complexity and variability of DDS. Case presentation: The first case is a 7‐month‐old male presenting with ambiguous genitalia, nephropathy, and intussusception. Genetic analysis identified a likely pathogenic heterozygous WT1 variant: c.1384C >T (p.Gln462Ter). Despite surgical interventions, treatment was delayed due to COVID‐19 restrictions, and the patient unfortunately passed away at 16 months during the lockdown period. The second case involves an 8‐month‐old female with normal external genitalia, a horseshoe kidney, bilateral renal masses, and recurrent hypotensive episodes. Genetic testing revealed a pathogenic heterozygous WT1 variant: c.453G >A (p.Trp151Ter). She was diagnosed with DDS–associated Wilms tumor and, despite aggressive management, passed away at 21 months. Conclusion: These cases underscore the importance of early diagnosis, multidisciplinary management, and personalized therapeutic approaches in DDS patients. Bilateral nephrectomy, renal transplantation, and monitoring for Wilms tumor are pivotal in improving prognosis, though variability in clinical presentations often complicates decision‐making.

Objectives: The Tandem t:slim X2 insulin pump with the Control‐IQ technology (Control‐IQ) is an automated insulin delivery (AID) system for glycemic control but has limited data in Saudi pediatric and young adult populations. We aim to evaluate the efficacy and safety of Control‐IQ therapy in children with insulin‐dependent diabetes and previously treated with multiple daily injections (MDIs). The primary outcome is to assess the change in HbA1c 6 months after initiating Control‐IQ technology. Methods: This prospective observational study evaluated children aged 2–14 years with insulin‐dependent diabetes who transitioned from treatment with MDI to the Control‐IQ technology in the diabetes clinic at the King Faisal Specialist Hospital and Research Centre (KFSHRC) in Saudi Arabia. Results: A total of 100 patients (44 boys and 56 girls; median age was 11 years) were included. Most (82%) had a history of severe hypoglycemia. Following Control‐IQ initiation, median HbA1c significantly decreased from 9.2% to 6.9% at 6 months (−25.0%; p < 0.001), accompanied by a 24.4% reduction in the daily insulin dose. Time in range (TIR) (70–180 mg/dL) improved from 45.6% to 68.8% (+23.2%; p < 0.001), while time in significant hypoglycemia (p < 0.001). At 6 months, 83% achieved ≥60% TIR, and 54% reached ≥70%. Adherence and engagement were high, with no severe hypoglycemia or discontinuations. Only 3% experienced mild/moderate ketoacidosis due to technical issues in the Control‐IQ. Conclusions: The findings demonstrated that Control‐IQ technology is both effective and safe in improving glycemic outcomes in children with insulin‐dependent diabetes in a real‐world clinical setting. However, successful implementation requires comprehensive training and continuous support.

Context: The aim of this study was to characterize the molecular genetics of 1α-hydroxylase deficiency in the highly consanguineous population of Saudi Arabia, hypothesizing that the results will show a unique CYP27B1 genotype. Methods: We collected data on a large cohort of patients diagnosed with 1α-hydroxylase deficiency from different parts of the country. These patients underwent molecular testing for CYP27B1 mutations. Results: A cohort of 45 patients from 29 unrelated families was studied. In 13 families (29 patients), more than one affected sibling was included (2-4 siblings) while the other 16 families had only a single patient per family. The patients included 24 females and 21 males with median age at time of presentation of 1 year and a current median age of 10 years. The clinical, biochemical and radiological profile was typical of 1α-hydroxylase deficiency. Molecular testing showed 10 mutations of different types in the 29 families. Four mutations were novel (p.(Trp257LeufsTer76), p.(Glu101Gln), p.(Gly398Ser), and p.(Arg206Cys)) while the other 6 mutations were previously described (p.(arg429Pro), p.(Phe443Profs*24), p.(Gln135Ter), p. (Gly102Glu), p.(Gln504Ter), and c.589 + 1G > A). Two of the previously reported mutations were from Saudi patients and have never been reported from other populations, increasing the number of novel/previously novel mutations to 6 of 10 mutations (60%). The most common mutation was c.1286G > C, p.(Arg429Pro) occurring in 22 patients from 15 unrelated families (51.7%). Conclusion: The molecular genetics of 1α-hydroxylase deficiency in Saudi Arabia is unique with several novel mutations of different types and a possible founder mutation.

Background: 3M syndrome (3MS) is a very rare autosomal recessive disorder characterized by short stature, distinctive facial features, and skeletal abnormalities. The condition is frequently underdiagnosed due to its nonspecific symptoms and normal neurocognitive development. Few reports exist on its clinical course and response to growth hormone (GH) therapy. Therefore, this study aims to describe the clinical features of Saudi patients with 3MS and to investigate the effects of growth hormone therapy on growth. Methods: We conducted a retrospective case series of 14 Saudi patients from 11 families with genetically confirmed 3MS at King Faisal Specialist Hospital and Research Centre in Riyadh. Results: The mean age at diagnosis was 5.4 years. Consanguinity was present in 79% of cases. The most frequently affected gene was CUL7 (57% of cases), followed by OBSL1 and CCDC8 . All variants were predominantly homozygous and classified as pathogenic or likely pathogenic. Clinical abnormalities included growth retardation, dental abnormalities, spinal abnormalities, and a characteristic facial appearance. GH therapy was administered to 10 children; 5 demonstrated a measurable improvement in growth velocity, while 5 did not respond or discontinued treatment. IGF-1 was within/low-normal in most tested cases, with two elevated results. Conclusion: Our study highlights the extensive phenotypic variability of 3MS and underscores the predominantly autosomal recessive inheritance pattern in this population. GH therapy may provide a growth benefit in select cases, although resistance and poor response remain a challenge. Genetic testing is crucial for accurate diagnosis, individualized management, and appropriate family counseling.