Rare diseases pose a substantial burden on healthcare systems, particularly in underserved regions such as the Middle East. The lack of access to genomic diagnostic services and personalised management plans exacerbates this challenge. To address this pressing issue, Al Jalila Children’s Specialty Hospital (AJCH) has taken a significant step by establishing a clinical genomics and genetic counseling facility. Housed within a multidisciplinary tertiary paediatric centre in the 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 summarise our experience including the diagnostic yield and implications for clinical management among this population.
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I will also highlight several new efforts toward enhancing the diagnostic efficacy and earlier identification of patients with rare diseases. These efforts include rapid whole genome sequencing for critically ill patients, newborn genetic screening, and whole genome long read sequencing. According to data from clinical standard testing on 1,000 patients with rare diseases (46.2 per cent 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 per cent (95 per cent CI, 29.7– 35.5 per cent). This was higher for genomic sequencing-based testing than chromosomal microarrays (37.9 per cent versus 17.2 per cent, 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 per cent of sequencing diagnoses. Of patients with positive genetic findings (N = 325), 67.7 per cent were less than five years of age, and 60 per cent were offered modified management and/or intervention plans.
Interestingly, 24 per cent of patients with positive genetic findings received delayed diagnoses (average age, 12.4 years; range from seven to 37 years), most likely due to a lack of access to genomic investigations in this region. One such genetic finding ended a 15-yearlong diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was then successfully treated using an experimental allogenic bone marrow transplant.
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Finally, we present cases with candidate genes within regions of homozygosity, likely underlying novel recessive disorders. Attendees can look forward to a feasibility study on a newly established pipeline for rapid whole genome sequencing (within 40 hours) for critically ill patients, as well as a discussion on a recent expansion of this pilot study, to include more patients over the next two years and generate evidence (clinical and economic utility) supporting implementation of this technology for patients in NICU/ PICU. I will also show preliminary results from our newborn genetic screening programme on the genetic epidemiology of spinal muscular atrophy (SMA) as a prototype for recessive diseases in the region. Finally, I will highlight the additional benefit of using whole genome long read sequencing in our setting. AJCH believes that early access to genomic diagnostic testing is a tenet to improving clinical outcomes for individuals living with rare diseases.
Facilitating timely and accurate diagnoses enables us to provide tailored treatment and care plans for genetically underrepresented populations in the Middle East. By bringing together advanced technology and expert genetic counseling, our facility strives to improve the quality of life for patients and families facing these medical challenges, fostering hope and empowering them with knowledge and support.
Dr. Ahmad Abou Tayoun is the Director of the Genomics Center of Excellence at Al Jalila Children’s Hospital, and an Associate Professor of Genetics at Mohammed Bin Rashid University of Medicine and Health Sciences. He will present 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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This article appears in Omnia Health magazine. Read the full issue online today.
