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.

A limited form of granulomatosis with polyangiitis in an ulcerative colitis patient receiving sulfasalazine.

This is a case report of a 31-year-old lady who is known to have ulcerative colitis for 15 years and was on mesalazine. She presented with periorbital swelling, sinusitis, epistaxis, and was found to have positive anti-neutrophil cytoplasmic antibody and anti-proteinase-3 of a high titer. Biopsy from the maxillary sinus showed chronic non-specific inflammation and biopsy from the periorbital fat revealed inflammation and granulomatous changes. She had no other organ involvement. She was diagnosed with a limited form of granumatosis and polyangiitis and treated with methotrexate and prednisolone. The symptoms disappeared after treatment.

Risk factors for hospital admission among COVID-19 patients with diabetes. A study from Saudi Arabia.

OBJECTIVES: To elucidate the risk factors for hospital admission among COVID-19 patients with type 2 diabetes mellitus (T2DM). METHODS: This retrospective study was conducted at the Prince Sultan Military Medical City, Riyadh, Saudi Arabia between May 2020 and July 2020. Out of 7,260 COVID-19 patients, 920 were identified as T2DM. After the exclusion process, 806 patients with T2DM were included in this analysis. Patients' data were extracted from electronic medical records. A logistic regression model was performed to estimate the risk factors of hospital admission. Results: Of the total of 806 COVID-19 patients with T2DM, 48% were admitted in the hospital, 52% were placed under home isolation. Older age between 70-79 years (OR [odd ratio] 2.56; p=0.017), ≥80 years (OR 6.48; p=0.001) were significantly more likely to be hospitalized compared to less than 40 years. Similarly, patients with higher HbA1c level of ≥9% compared to less than 7%; (OR 1.58; p=0.047); patients with comorbidities such as, hypertension (OR 1.43; p=0.048), cardiovascular disease (OR 1.56; p=0.033), cerebrovascular disease (OR 2.38; p=0.016), chronic pulmonary disease (OR 1.51; p=0.018), malignancy (OR 2.45; p=0.025), chronic kidney disease (CKD) IIIa, IIIb, IV (OR 2.37; p=0.008), CKD V (OR 5.07; p=0.007) were significantly more likely to be hospitalized. Likewise, insulin-treated (OR 1.46; p=0.03) were more likely to require hospital admission compared to non-insulin treated patients. CONCLUSION: Among COVID-19 patients with diabetes, higher age, high HbA1c level, and presence of other comorbidities were found to be significant risk factors for the hospital admission.

Genetic Polymorphisms in Transforming Growth Factor-ß, Interferon-γ and Interleukin-6 Genes and Susceptibility to Behcet's Disease in Saudi Population.

BACKGROUND: Behcet's disease (BD) is a complex, inflammatory, immune-mediated multi-systemic disease of unknown etiology. Cytokines play major roles in the pathophysiology of BD, and its production may be affected by polymorphism in cytokine genes. Hence, the present study was planned to investigate any possible association between the polymorphism in TGF-ß, IFN-γ, and IL-6 genes and BD in the Saudi population. MATERIALS AND METHODS: The present study includes 79 BD cases and 117 age-matched controls. Polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation systems (ARMS) PCR methods were used for polymorphic analysis. RESULTS: The heterozygous (CT) and (CT+TT) combined genotypes of TGF-ß (509-C/T), heterozygous (AT), variant (TT), and (AT+TT) combined genotypes of IFN-γ (874-A/T) were significantly (P<0.05) associated with BD in the Saudi population. No significant differences were observed for IL-6 (174-G/C) genotypes and alleles between BD cases and controls. Gender does not reflect any significant genotypic and allelic association with males and females. CONCLUSION: CT genotype of TGF-ß, and AT and TT genotypes of IFN-γ could be associative genetic risk factors for BD in Saudis. Regulatory region polymorphism in cytokines gene can increase inflammation and deregulated immune response, which could be risk factor for BD.

Severe aortic regurgitation complicating Takayasu's arteritis.

We present an uncommon case of a 48-year-old female patient with symptomatic presentation of a severe aortic regurgitation with aneurysm of the ascending aorta and progressive dyspnea. Detailed investigation of laboratory tests and imaging identified Takayasu's arteritis (TA) as the underlying etiology. Computed tomography scan revealed complete occlusion of the right carotid artery as well as stenosis at the origins of left subclavian and vertebral arteries. In addition, cardiac magnetic resonance angiogram showed aneurysm at the proximal segment of right subclavian artery. Intervention with corticosteroids effectively diminished the need for immediate surgical intervention. Treating physicians should always consider differential diagnosis of TA in the presence of atypical clinical findings in all patients with cardiac problems especially when there is valve involvement.