Genotype and Phenotype of Adenosine Deaminase 2 Deficiency: a Report from Saudi Arabia.

Adenosine deaminase 2 deficiency (DADA2), a rare and potentially fatal systemic autoinflammatory disease, is characterized by low or lack of ADA2 activity due to ADA2 mutations. DADA2 symptoms are variable and include vasculitis, immunodeficiency, and cytopenia. Minimal data are available from Saudi Arabia. This retrospective study conducted at seven major tertiary medical centers examined the phenotypic and genotypic variabilities, clinical and diagnostic findings, and treatment outcomes among 20 Saudi patients with DADA2 from 14 families. The median age of the study cohort was 9.5 years (4-26 years). The clinical presentation was before the age of 5 months in 25% of patients. Homozygous c.1447-1451del mutation was the most frequent ADA2 alteration (40%), followed by c.882-2A:G (30%). All tested patients exhibited absent or near-absent ADA2 activity. Phenotypic manifestations included stroke (40%), hematological abnormalities (95%), lymphoproliferation (65%), and recurrent infection (45%). Five and three patients had extracranial vasculitis features and Hodgkin lymphoma, respectively. Atypical manifestations included growth retardation (30%) and transverse myelitis. Anti-tumor necrosis factor (anti-TNF) therapy was the main treatment. Some patients underwent blood transfusion, splenectomy, cyclosporine and colony-stimulating factor therapies, and hematopoietic stem cell transplantation due to anti-TNF therapy failure. Fulminant hepatitis and septic multiorgan failure caused mortality in three patients. Thus, this study revealed the variability in the molecular and clinical characteristics of DADA2 in the study cohort with predominant aberrant hematological and immunological characteristics. Consensus diagnostic criteria will facilitate early diagnosis and treatment. Additionally, disease registries or large prospective studies are needed for evaluating rare disease complications, such as cancer.

Paediatric orthopaedic surgery during the SARS-CoV-2 pandemic. A safe and pragmatic approach to service provision.

The SARS-COV-2 pandemic has brought unparalleled challenges to healthcare provision. Being a newly discovered virus, there is a lack of previous experience and published evidence to guide healthcare providers on how to deliver services. We would like to share our approach to service delivery in a newly open children's hospital in the United Arab Emirates with a particular focus on paediatric orthopaedic services.

Fludarabine-based reduced-intensity conditioning regimen for hematopoietic stem cell transplantation in pediatric patient with IL10 receptor deficiency.

IL-10R deficiency results in severe immune dysregulation. Herein, we describe the successful treatment of a girl aged 6.8 years with IL10R deficiency by using RIC prior to HSCT from a matched unrelated donor. The regimen was well tolerated, the engraftment was completely attained. On a follow-up of 7 months, the patient remained in good medical conditions with full donor chimerism. All complications before HSCT were completely resolved and her growth was accelerated. RIC regimen might be adequate to induce permanent engraftment and avoid severe organ toxicity in IL-10R deficiency patients.

Wolman's disease presenting with secondary hemophagocytic lymphohistiocytosis: a case report from Saudi Arabia and literature review.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal syndrome that is characterized by strong activation of the immune system from hyperinflammatory cytokines. Symptoms of HLH patients include fever, hepatosplenomegaly, cytopenia, and hyperferritinemia. Inherited HLH is classified as primary, whereas secondary HLH (sHLH) occurs when acquired from non-inherited reasons that include severe infection, immune deficiency syndrome, autoimmune disorder, neoplasm, and metabolic disorder. Wolman's disease (WD) is a rare and fatal infantile metabolic disorder caused by lysosomal acid lipase deficiency, that exhibits similar clinical signs and symptoms as HLH. This paper reports the case of an infant diagnosed with WD and who presented with sHLH. CASE PRESENTATION: A 4-month-old infant presenting with hepatosplenomegaly, failure to thrive, and other abnormalities. WD diagnosis was confirmed by the presence of the LIPA gene homozygous deletion c.(428 + 1_967-1)_(*1_?)del. The infant also met the HLH-2004 diagnostic criteria. CONCLUSIONS: Metabolic disorder such as WD should be investigated in infants fulfilling the HLH criteria to diagnose the underlying condition. More studies are needed to understand the link between WD and sHLH and to identify appropriate therapies.

Investigating soluble CD40 ligand as a prognostic factor among acute coronary syndromes patients: A multi-center prospective case-control study.

Soluble CD40 ligand (sCD40L) is a protein that plays a crucial role in the inflammatory response associated with the development and progression of acute coronary syndrome (ACS). Recent studies have suggested that sCD40L may be a useful prognostic factor for ACS, but the data are conflicting. This study aimed to investigate the potential of sCD40L as a prognostic marker among ACS patients and provide valuable insights for clinical practice. To our knowledge, this is the first study of its type in the Arabic World. A multi-center prospective case-control study was conducted in Damascus, Syria, involving 158 participants with different ACS subtypes (STEMI, NSTEMI, UA) and a control group of healthy individuals. Sociodemographic data, medical history, and sCD40L levels were collected. The predictive ability of sCD40L for ACS, STEMI, NSTEMI, and UA was assessed using receiver operating characteristic (ROC) curves. Statistical analysis was performed using IBM SPSS version 25. The study included 58 STEMI, 33 NSTEMI, 36 UA patients, and 30 healthy individuals. The mean age of participants was 55 years (SD 10.7 years). Analysis of sCD40L levels revealed significantly higher concentrations in ACS patients compared to the control group (P < .001). ROC curve analysis demonstrated that sCD40L had a significant predictive ability for ACS, STEMI, and NSTEMI (P < .05), while its predictive value for UA was not statistically significant. This study provides evidence supporting the potential of sCD40L as a prognostic factor in ACS. The elevated levels of sCD40L observed in these subtypes indicate its potential usefulness in risk stratification and predicting adverse cardiovascular events. Further investigations are warranted to establish standardized sCD40L cutoff values and evaluate its clinical implications in the management of ACS patients.

Children with sickle cell disease: are they protected from serious COVID-19?

Background: COVID-19, the pandemic that hit the world in 2020, resulted in millions of deaths, with the elderly and adults succumbing to the disease more often than children. However, the presence of underlying morbidities increased the risk of death. Sickle cell disease (SCD) was previously classified as a major risk factor for severe COVID-19 disease. However, presently, there are only a limited number of studies that identify the clinical course of children with SCD and COVID-19. Methods: We conducted a retrospective observational study on children with SCD admitted due to COVID-19 at three different institutions in Saudi Arabia between March 2020 and March 2022. We studied the demographic and clinical characteristics of patients admitted to the hospital. Results: Seventy-six patients with SCD had PCR-confirmed SARS-CoV-2 during the study period; 50.0% of our patient population were children (6-12 years old). Gender was evenly distributed, with 53.9% girls and 46.1% boys. Symptoms more commonly related to the COVID-19 infection included fever, cough, malaise, and vomiting. Chest x-ray findings revealed mild and non-specific symptoms only in approximately one-third (28) of the included children. The most common symptoms associated with SCD were vaso-occlusive crisis (47.4%) and abdominal pain (11.8%). The overall general appearance of most of the patients was reassuring. The median length of hospital stay was 4.2 ± 2.7 days. The mean white blood cell count was 11.4 ± 5.2 × 109/L, and the mean hemoglobin level was 8.3 ± 1.5 g/dl. Despite the fact that higher levels of mean D-dimer, lactate dehydrogenase, and ferritin were reported in these patients, the clinical outcome was not affected. All recruited patients received hydroxyurea as maintenance therapy. The outcome of our study was reassuring, with no significant morbidity or mortality observed among the recruited patients. Conclusion: Despite SCD being a chronic disease with known specific complications, there has been a claim that COVID-19 infection adds further risk. The results of this study suggest that the overall outcome of COVID-19 was favorable, with no reported mortality. Further research is needed to understand the factors that contributed to this favorable outcome. In children with SCD, it is still questionable whether hydroxyurea is one of the protective factors against severe COVID-19. Validation through large-scale research is recommended.

Adolescent-Acquired Flatfeet: The Tip of the Iceberg.

There has been a substantive change in our lifestyle over the last two decades. The widespread availability of entertaining digital devices created an unhealthy culture of a sedentary lifestyle, with our children hooked to their digital devices for countless hours. The mental and social consequences have been well explored in several studies. Leading a sedentary lifestyle has been shown to be associated with obesity, diabetes, cardiovascular diseases, and even early death. The adolescent-acquired flatfeet is another addition to the ever-growing list. The lack of physical activities among children nowadays has led to a pandemic of long muscles tightness in children, particularly during the growth spurt. The mismatch between the long bones and adjacent muscles growth caused relative muscles shortening, particularly the muscles that cross more than one growth center, such as the hamstring muscles and gastrocnemius muscles. As a result, it has become common to see children who cannot touch the floor on forward bending because of hamstring muscles tightness or inability to walk on their heels because of gastrocnemius muscles tightness. While muscles tightness is relatively benign, its consequences, such as adolescent-acquired flatfeet, are not. In this review, we have explored the condition, its prevention, and treatment to raise awareness among the public and professionals.

Escalated Dose Donor Lymphocyte Infusion Treatment in Patients with Primary Immune Deficiencies After HSCT with Reduced-Intensity Conditioning Regimen.

OBJECTIVE/BACKGROUND: Mixed chimerism is a major concern after allogenic hematopoietic stem cell transplantation (HSCT) using a reduced-intensity conditioning (RIC) regimen in primary immunodeficiencies (PIDs). A donor lymphocyte infusion (DLI) escalating dose regimen has been developed with the aim of reducing toxicity while preserving efficacy. However, the graft-versus-host disease (GvHD) development remains the most common and adverse effect of DLI and continues to be a limiting factor in its application, especially nonmalignant diseases such as PIDs. We prospectively evaluated PID patients after HSCT using RIC in Childrens Medical Center, who were candidates for an escalating dose of DLI for MC from 2016 to 2018. METHODS: With the median follow-up of 16.4 months, 12 patients (nine males and three females) with a median age of 3.72 years received DLI. The median number of DLI was 3.2 (range, 1-5), the maximum and total dose of DLIs administered per patient were 3.6 × 107 (range, 1-5) cells/kg CD3+ and 9.3 × 107 (range, 1-15) cells/kg CD3+ cells, respectively. RESULTS: Median donor chimerism at baseline before the DLIs was 41% (range, 11-73%), patients received DLIs at a median of 105 (range, 37-230) days and 52 (range, 3-168) days after the HSCT and onset of the MC, respectively. At the final assessment, six (54.5%) patients improved after DLIs at a median of 47.3 days. CONCLUSION: PID patients may benefit from DLI with an escalating dose regimen, but the GvHD development remains a concern during the DLI, and the optimum dose and frequency must be standardized.

Successful Kidney Transplant for Nephropathic Cystinosis in a Patient with Von Willebrand Disease Type III: The First Case Report.

Nephropathic cystinosis (NC) is a rare autosomal recessive disease, which causes cysteine-crystals accumulation with progression to end-stage renal disease (ESRD). Von willebrand disease (VWD) type III is a rare subtype of von willebrand factor (VWF) abnormality, which is characterized by severe reduction of VWF and factor VIII activity. A 16-year-old patient with NC and VWD type III presented with uremic symptoms due to ESRD. Dialysis access was inserted and followed by hemodialysis (HD) for 4 months with a proper infusion of blood products. While renal transplant remains the treatment of choice of NC and superior to chronic HD, bleeding complications were a major concern in this case with coexisting VWD type III. However, with the meticulous implementation of the Hematology team's daily recommendations, renal transplantation was successfully performed. This is the first case that mentions a new association between two inherited rare disorders, NC and VWD type III, and this entity has not been reported before. Moreover, successful kidney transplantation in our patient supports the possibility of these procedures in hereditary clotting disorders.

Unusual presentation of COVID-19 in a child complicated by massive acute pulmonary embolism and lung infarction.

The Novel Coronavirus 2019 (SARSCoV- 2), which was first reported on in Wuhan, China, in late December 2019, causes a respiratory illness called COVID- 19 Disease. COVID-19 is most likely causing a hypercoagulable state, however the prevalence of acute venothromboembolism is still unknown. Limited data suggest pulmonary microvascular thrombosis may play a role in progressive respiratory failure. Here, we report a case of a child with an unusual presentation of COVID-19 presented initially by dry cough without fever and complicated by massive acute pulmonary embolism and lung infarction and treated successfully by hydroxychloroquine and azithromycin, in addition to anticoagulant therapy.

Routine Preoperative Coagulation Tests in Children Undergoing Elective Surgery or Invasive Procedures: Are They Still Necessary?

INTRODUCTION: Preoperative coagulation screening tests in pediatric patients was once routine clinical practice globally and still used as standard practice in some countries before surgical procedures to assess of perioperative bleeding risk. OBJECTIVE: The study aimed to evaluate unselected routine preoperative coagulation testing in children undergoing elective or invasive surgery to predict abnormal perioperative bleeding. The study also aimed to provide a rational approach of determining bleeding and family history of coagulation disorders as a predictive risk for bleeding. METHODS: This retrospective study conducted between 2014 and 2015 (1 year) on normal healthy children aged under 15 years admitted to the hospitals for elective mild to intermediate surgery or invasive procedures. We reviewed and collected the details of the clinical history, previous surgery, trauma, family history, detail of anti-thrombotic medication and coagulation tests performed (prothrombin time (PT), the activated partial prothrombin time (APTT), and international normalized ratio (INR)) at the time of admission. RESULTS: Among 2078 cases, 1940 cases had normal coagulation tests (93.4%), 77 cases had abnormal coagulation results (3.7%), and 61 patients underwent surgery without preoperative coagulation screening (2.9%). In 15 of 77 patients, coagulation tests were normal on repeat testing. A total of 52 were confirmed to have abnormal screening testing. Among these 52 cases, 45 had normal factors assay; where seven patients had abnormal factors assay. Postoperative bleeding occurred only in three cases (0.14%), two cases due to surgical procedures with normal preoperative testing and one due to hemophilia A which was detected postoperatively as no preoperative testing was performed. CONCLUSIONS: Routine coagulation screening before surgery or invasive procedures to predict perioperative bleeding in unselected patients is not recommended. Our study emphasizes that selective preoperative testing is more appropriate. Selective criteria for consideration of the latter includes physical examination, type of surgery, family and bleeding history, and concomitant use of antiplatelet and anti-thrombotic therapy.