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.

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.

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.

Molecular characterization of novel splice site mutation causing protein C deficiency.

Congenital protein C deficiency is an inherited coagulation disorder associated with an elevated risk of venous thromboembolism. A Saudi Arabian male from a consanguineous family was admitted to neonatal intensive care unit in his first days of life because of transient tachypnea and hematuria. Laboratory investigations determined low platelet and protein C deficiency. Direct sequencing of PROC gene and RNA analysis were performed. Analysis of factor V Leiden (G1691A) and factor II (G20210A) mutations was also done. Novel homozygous splice site mutation c.796+3A>T was detected in the index case and segregation was confirmed in the family. RNA analysis revealed the pathogenicity of the mutation by skipping exon 8 of PROC gene and changing the donor splice site of the exon. Detection of the molecular cause of protein C deficiency reduces life threatening and facilitates inductive carrier testing, prenatal and preimplantation genetic diagnosis for families.