Rare diseases place a huge burden on the health care system, especially in underserved areas such as the Middle East. Lack of access to genomic diagnostic services and personalized management plans exacerbates this challenge. To address this pressing issue, Al Jalila Children’s Hospital (AJCH) has taken a significant step by establishing a clinical genomics and genetic counseling facility. Housed in a multidisciplinary tertiary pediatric center in UAE, our facility is dedicated to diagnosing and managing patients with rare diseases. Standard clinical genomic investigations at our facility include exome-based sequencing, chromosomal microarrays and/or targeted testing. In my session “Current State of Genomic Diagnostics in Pediatrics” at Medlab Asia 2023, I will summarize our experience including the diagnostic results and implications for clinical management among this population.
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I will also highlight some of the recent efforts to improve diagnostic efficacy and early identification of patients with rare diseases. These efforts include rapid whole genome sequencing for critically ill patients, newborn genetic screening, and whole genome length sequencing. According to data from standard clinical trials on 1,000 patients with rare diseases (46.2 percent women; mean age, 4.6 years) representing 47 countries mainly from the Arabian Peninsula, Levant, Africa, and Asia, the cumulative diagnostic yield was 32, 5 percent (95 percent CI, 29.7–35.5 percent). This was higher for genome sequencing-based assays than for chromosomal microarrays (37.9 percent versus 17.2 percent, P = 0.0001) across all indications, consistent with a higher burden of single-gene disorders. Of the 221 Mendelian disorders identified in this cohort, the majority (N = 184) were found only once, and those that were recessively inherited accounted for ~62 percent of the sequencing diagnoses. Of the patients with positive genetic findings (N = 325), 67.7 percent were aged less than five years, and 60 percent were offered a modified management and/or intervention plan.
Interestingly, 24 percent of patients with positive genetic findings received a delayed diagnosis (mean age, 12.4 years; ranged from seven to 37 years), most likely due to lack of access to genomic investigations in this region. One such genetic finding ended a 15-year diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was subsequently successfully treated using experimental allogeneic bone marrow transplant.
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Finally, we present cases with candidate genes within the homozygosity region, which likely underlies the novel recessive disorder. Participants can look forward to feasibility studies on the newly established pipeline for rapid (within 40 hours) whole genome sequencing for critically ill patients, as well as discussions about the recent expansion of this pilot study, to include more patients over the next two years. years and generate evidence (clinical and economic utility) supporting the application of this technology to patients in the NICU/PICU. I will also present early results from our newborn genetic screening program on the genetic epidemiology of spinal muscular atrophy (SMA) as a prototypical recessive disease in the region. Finally, I will highlight the additional benefit of using whole genome long read sequencing in our setting. The AJCH believes that early access to genomic diagnostic testing is a principle for improving clinical outcomes for individuals living with rare diseases.
Facilitating timely and accurate diagnosis allows us to provide customized care and treatment plans for genetically underrepresented populations in the Middle East. By bringing together state-of-the-art technology and expert genetic counseling, our facility strives to improve the quality of life for patients and families facing this medical challenge, inspiring hope and empowering them with knowledge and support.
Ahmad Abou Tayoun is Director of the Genomics Center of Excellence at Al Jalila Children’s Hospital, and Associate Professor of Genetics at Mohammed Bin Rashid University of Medicine and Health Sciences. He will be presenting his topic “Current Genomic Diagnosis in Paediatrics” at the Molecular Diagnostics and Genomics conference on August 16 at Medlab Asia 2023.
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