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.

Here, we report the case of a rare and complex disorder, rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neuroendocrine tumor (ROHHADNET) syndrome, in a threeyear-old girl with no significant medical history. This is the first such case reported from the UAE. ROHHADNET is a rare disorder of respiratory control and autonomic nervous system regulation with endocrine abnormalities. It typically presents in children older than 18 months with rapid weight gain. This is a challenging diagnosis as there is no clear diagnostic test, and treatment is essentially supportive. This report describes a case of ROHHADNET syndrome in a previously well child who presented with rapid weight gain followed by ophthalmoplegia, dysphagia, electrolyte disturbance, and other comorbidities. The paper outlines in detail the clinical course, investigations, and management of ROHHADNET syndrome. Cerebrospinal fluid analysis revealed oligoclonal bands, which have been reported in only two other cases of ROHHADNET syndrome. Our goal in reporting this case is to increase awareness of this condition among clinicians to facilitate early diagnosis and timely management.