We describe a case series of five infants (age range: 1–90 days; 4 females and 1 male) who presented to Al Jalila Children’s intensive care units (ICU) with complex multisystem disorders. Patients were Emirati, Kenyan, Jordanian, Filipino, or Pakistani. Trio rapid whole genome sequencing (rWGS) was performed on all five patients and their parents within the hospital’s genomics facility. Results were returned within ~37 h from blood sample draws and were diagnostic in 3 out of 5 patients. Positive findings were a homozygous pathogenic variant in POMT1 gene causing muscular dystrophydystroglycanopathy, a mosaic tetrasomy of the short arm of chromosome 12 (12p13.33p11.1) causing Pallister-Killian syndrome, and compound heterozygous pathogenic variants in the LIPA gene causing lysosomal acid lipase deficiency and Wolman disease. The rWGS analysis provided fast and precise diagnostic findings in those 3 patients and also aided in devising better management plans for them in the intensive care setting. For example, the 3-month-old infant with pathogenic variants in the LIPA gene is now a candidate for an FDA-approved, potentially lifesaving enzyme replacement therapy (sebelipase alfa). Our case series emphasize the feasibility and utility of rWGS in pediatric intensive care setting, in a diverse population that has long been underserved in genomic services. Significant investments in local healthcare infrastructure are needed, globally, for more equitable access of genomic medicine among vulnerable patients.
Key Points Question What are the clinical, genetic, and laboratory characteristics of Middle Eastern patients with multisystem inflammatory syndrome in children (MIS-C)? Findings In this cohort study of 45 patients with MIS-C of primarily Arab and Asian origins, an enrichment of rare, likely deleterious immune-related genetic variants was found, with a possible association between genetic findings and MIS-C onset and resistance to treatment. Meaning These findings suggest that comprehensive genetic profiling of patients with MIS-C of diverse ethnicities is essential to characterize the genetic contribution to this disease.
Background Rare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans. Methods We established a clinical genomics and genetic counseling facility, within a multidisciplinary tertiary pediatric center, in the United Arab Emirates to locally diagnose and manage patients with rare diseases. Clinical genomic investigations included exome-based sequencing, chromosomal microarrays, and/or targeted testing. We assessed the diagnostic yield and implications for clinical management among this population. Variables were compared using the Fisher exact test. Tests were 2-tailed, and P < .05 was considered statistically significant. Results We present data on 1000 patients with rare diseases (46.2% females; average age, 4.6 years) representing 47 countries primarily from the Arabian Peninsula, the Levant, Africa, and Asia. The cumulative diagnostic yield was 32.5% (95% CI, 29.7–35.5%) and was higher for genomic sequencing-based testing than chromosomal microarrays (37.9% versus 17.2%, P = 0.0001) across all indications, consistent with the higher burden of single gene disorders. Of the 221 Mendelian disorders identified in this cohort, the majority (N = 184) were encountered only once, and those with recessive inheritance accounted for ~ 62% of sequencing diagnoses. Of patients with positive genetic findings (N = 325), 67.7% were less than 5 years of age, and 60% were offered modified management and/or intervention plans. Interestingly, 24% of patients with positive genetic findings received delayed diagnoses (average age, 12.4 years; range 7–37 years), most likely due to a lack of access to genomic investigations in this region. One such genetic finding ended a 15-year-long diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was then successfully treated using an experimental allogenic bone marrow transplant. Finally, we present cases with candidate genes within regions of homozygosity, likely underlying novel recessive disorders. Conclusions Early access to genomic diagnostics for patients with suspected rare disorders in the Middle East is likely to improve clinical outcomes while driving gene discovery in this genetically underrepresented population.
Objective: This study was conducted to estimate the common signs and symptoms present in patients with vitamin D deficiency at a children's specialty hospital in Dubai, United Arab Emirates (UAE).Methods: This descriptive cross-sectional study (n = 805) examined patients aged <18 years with a serum 25hydroxy vitamin D concentration of <50 ng/mL and presenting to the hospital between 2017 and 2018. Variables (age, gender, nationality, vitamin D levels, signs and symptoms, and primary complaint) were described using frequencies and mean values (SD). Chi-square and Kruskal-Wallis tests were conducted.Results: Among the 805 patients, 315 (39.2%) had vitamin D deficiency (<20 ng/mL). Regarding the symptoms of these 315 patients, 26% (n = 82) of them were asymptomatic, 13.3% (n = 42) of them had endocrine symptoms and other/rare symptoms, and 11.7% (n = 37) of them had gastrointestinal symptoms. The least common symptoms were found in the mixed category (mixed symptoms of different body systems), consisting of 3.5% (n = 11) of patients. Vitamin D deficiency was more common among female patients (44.8%) and Emiratis (40.5%), and the average age for patients to have vitamin D deficiency was nine years.Conclusion: To our knowledge, this is one of the first studies in the United Arab Emirates to focus on and examine patients with low vitamin D levels in detail. Determining the most frequent symptoms is helpful for healthcare practitioners because our results showed that most patients with the deficiency were asymptomatic. Hence, we recommend performing regular checkups for healthy and asymptomatic children to detect vitamin D deficiency before they show any symptoms.
Objective This is a comprehensive characteristic study of Kawasaki disease (KD) and Multi system inflammatory syndrome in children (MIS-C) in the Middle East that creates a formula to differentiate between the two. Methods We conducted a descriptive comparative study of KD and MIS-C in the United Arab Emirates. Retrospective MIS-C and KD cohorts were recruited between January 2017 until August 2021.We compared clinical and laboratory characteristics between both groups. Our data were compared with 87 patients with KD or MIS-C from the literature. Results We report on123 patients. Sixty-seven (54%) met the criteria for KD (36 male, 43 Arab), and fifty-six (46%) met the criteria for MIS-C (28 male, 35 Arab). The median age was 2.2 years range (0.15–10.7) in the KD group and 7.3 years (0.7–15.2) in the MIS-C group (P < 0.001). The clinical features on admission showed an increase in gastrointestinal manifestations in MIS-C compared with KD (84% vs. 31%, P < 0.001). Laboratory tests on admission revealed a significant increase in the following tests in KD compared with MIS-C; white blood cells (mean 16.30 10(3) µcL vs. 11.56 10(3) µcL, P < 0.001), absolute neutrophils (mean 10.72 10(3) µcL vs. 8.21 10(3) µcL, P 0.008), absolute lymphocytes (mean 3.92 10(3) µcL vs. 2.59 10(3) µcL, P 0.003), erythrocyte sedimentation rate (mean 73 mm/hr vs. 51 mm/hr, P < 0.001) and platelets (median {390 10(3) µcL vs. 236 10(3) µcL, P < 0.001}). In contrast, procalcitonin and ferritin were increased in the MIS-C group (2.4 )ng/mL, 370 ng/mL; P < 0.001). Cardiac dysfunction and admission to the pediatric intensive care unit were higher in MIS-C than in KD (21% vs. 8% and 33% vs. 7.5%, respectively, P < 0.001). Conclusion This study showed vast similarities between KD and MIS-C, suggesting that they lie along the same clinical spectrum. However, there are several differences between the two disease entities suggesting that MIS-C most likely represents a new severe variant of KD. Based on our findings in this study, we created a formula to differentiate between KD and MIS-C.
BACKGROUND Rare diseases collectively impose significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans. METHODS We established a clinical genomics and genetic counselling facility, within a multidisciplinary tertiary pediatric center, in the United Arab Emirates to locally diagnose and manage patients with rare diseases. Clinical genomic investigations included exome-based sequencing, chromosomal microarrays, and/or targeted testing. We assessed the diagnostic yield and implications for clinical management among this population. RESULTS We present data on 529 patients with rare diseases (47% females; Average age, 4 years) representing 41 countries primarily from the Arabian Peninsula, the Levant, Africa, and Asia. The cumulative diagnostic yield was 35.7% (95% CI, 31.8% - 39.9%) and was higher for genomic sequencing-based testing than chromosomal microarrays (41.2% versus 16.9%, P=0.0001) across all indications, consistent with the higher burden of single gene disorders. Of the 124 Mendelian disorders identified in this cohort, the majority (N = 110) were encountered only once, and those with recessive inheritance accounted for ~60% of sequencing diagnoses. Of patients with positive genetic findings (N = 189), 71.9% were less than 5 years of age, and 65.6% were offered modified management and/or intervention plans. Interestingly, 18.5% of patients with positive genetic findings received delayed diagnoses (age range 7 to 37 years), most likely due to lack of access to genomic investigations in this region. One such genetic finding ended a 15-year long diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was then successfully treated using an experimental allogenic bone marrow transplant. Finally, we present cases with candidate genes within regions of homozygosity, likely underlying novel recessive disorders. CONCLUSIONS Early access to genomic diagnostics for patients with suspected rare disorders in the Middle East is likely to improve clinical outcomes while driving gene discovery in this historically underrepresented population.
Bacillus Calmette-Guérin (BCG) vaccine is a live attenuated vaccine used globally since 1921, and in the United Arab Emirates (UAE), it is administered to all newborns within the first few days of life for well-established benefits. BCG osteomyelitis is a rare complication that should be considered while assessing osteomyelitis in children. This report describes three cases of BCG osteomyelitis involving proximal metaphysis of the humerus in 11 months and three months old immunocompetent male infants and the left proximal tibia in a two-year-old immunocompetent female. To the best of our knowledge, these are the first cases to be reported in the UAE. The report outlines in detail how to make a timely diagnosis by explaining the insidious clinical presentation of BCG osteomyelitis, including its radiologic, microbiologic, and histologic aspects. As well, it outlines the treatment course carried out for these three patients. As such, this report will aid physicians in staying vigilant for such rare complication and commencing early treatment.
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