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.

Case report: Durable response to ruxolitinib in a child with TREX1-related disorder.

Background: JAK inhibitors are useful in treating interferonopathies, presumably because they downregulate the JAK/STAT signaling. There are limited studies about the safety and effectiveness of using JAK inhibitors in children with TREX1-related disorders. Case presentation: We report an 8-year-old female who presented at five years of age with features suggestive of hemophagocytic lymphohistiocytosis (HLH)-like disorder. The infectious disease workup was negative. Neurological assessment was normal. A brain CT scan was performed because of headache. It showed a faint subcortical calcification at right frontal lobe and almost symmetrical calcification within the basal ganglia. Brain MRI showed bilateral symmetrical globus pallidus, high T1 signal intensities, and a few scattered nonspecific FLAIR hyperintensities in subcortical and deep white matter. IVIG as an immune modulating agent was administered initially which led to the resolution of fever, improvement of blood count parameters, inflammatory markers, and normalization of liver enzymes. The child remained afebrile with no significant events for several months, then had disease flare up. The patient was started on pulse methylprednisolone 30 mg/kg for three days, then continued on 2 mg/kg. Whole exome sequencing revealed a novel heterozygous missense TREX1 mutation NM_016381.3:c.223G > A p.(Glu75Lys). The child was started on ruxolitinib, 5 mg orally twice daily. The child has prolonged, durable remission after initiating ruxolitinib with no adverse effects. Steroids were tapered off and the patient is no longer on IVIG. The patient is still on ruxolitinib for more than two years. Conclusion: This case highlights the potential role of ruxolitinib in the treatment of TREX1-related disorders. A longer follow-up period is required to evaluate the long-term outcome.

Acquired Saccular Abdominal Aortic Aneurysm in a 10-Year-Old Child: A Case Report and Literature Review.

An abdominal aortic aneurysm (AAA) is a confined dilatation involving the abdominal aorta. The incidence is rare and the etiology is unknown. Cases associated with conditions like Kawasaki, connective tissue, Behcet's diseases, and vasculitis are considered acquired. Our patient had a clinical criterion of Behcet's disease. Management involves a surgical approach. Endovascular intervention is not an option here, as the aneurysm is close to the bifurcation evident in computed tomography angiogram scans. Usually, they have good long-term outcomes. In our paper, we aim to describe the clinical presentation, management approach, and the outcome of our patient with an acquired AAA.

Management of Hepatitis A-induced Macrophage Activation Syndrome With Anakinra in Systemic Juvenile Idiopathic Arthritis: A Case Report.

Macrophage activation syndrome (MAS) is a severe and life-threatening complication of rheumatic diseases in childhood. It is most associated with systemic juvenile idiopathic arthritis (sJIA). We present the case of a nine-year-old boy diagnosed with sJIA for six years who developed MAS triggered by hepatitis A. He was managed with anakinra and corticosteroids. Some of the clinical features of MAS occur late in the disease course, so clinicians should keep a high index of suspicion to initiate treatment early. This case highlights that anakinra and corticosteroid use in treating MAS is effective and has a good safety profile for pediatric patients.

IgG4-related sclerosing mesenteritis in a 7-year-old Saudi girl.

Sclerosing mesenteritis (SM) is a rare, benign inflammatory disorder of unknown etiology, affecting the membranes of the digestive tract that involves lymphoplasmacytic inflammation, fat necrosis, and fibrosis of the mesentery. We report a child patient with a history of recurrent abdominal pain and fever who was found to have an intra-abdominal mass suspicious for malignancy. A tissue biopsy revealed the diagnosis of SM associated with IgG4-related systemic disease. The patient is currently maintained on 5 mg prednisone daily and no recurrence of symptoms was noted during the 24-month follow-up period. We emphasize, therefore, that SM can present clinical challenges and the presence of SM should cue clinicians to search for other coexisting autoimmune disorders that can have various outcomes.