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Updated: Sep 22, 2025
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Rapid whole genome sequencing of critically ill pediatric patients from genetically underrepresented populations
Nour Halabi1, Sathishkumar Ramaswamy1, Maha El Naofal1
1Al Jalila Genomics Center of Excellence, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates.
Insights
Rapid whole genome sequencing (rWGS) rapidly diagnosed complex genetic disorders in 3 of 5 infants in intensive care. This highlights rWGS utility in diverse pediatric populations, enabling timely management and treatment.
Area of Science:
- Genomic Medicine
- Pediatric Intensive Care
- Rare Diseases
Background:
- Complex multisystem disorders in infants often pose diagnostic challenges in pediatric intensive care units (ICUs).
- Trio rapid whole genome sequencing (rWGS) offers a potential solution for rapid genetic diagnosis in critically ill children.
- Genomic services have historically underserved diverse global populations.
Observation:
- A case series of five infants (1-90 days) with complex multisystem disorders presented to the ICU.
- Trio rWGS was performed on patients and their parents, with results returned within approximately 37 hours.
- The patients represented diverse ethnicities, including Emirati, Kenyan, Jordanian, Filipino, and Pakistani.
Findings:
- rWGS yielded diagnostic results in 3 out of 5 infants.
- Identified genetic causes included a POMT1 pathogenic variant (muscular dystro-dystroglycanopathy), mosaic tetrasomy 12p (Pallister-Killian syndrome), and LIPA pathogenic variants (lysosomal acid lipase deficiency/Wolman disease).
- Fast and precise diagnoses facilitated improved management plans in the ICU setting.
Implications:
- rWGS demonstrated feasibility and utility in a pediatric ICU, particularly for diverse and underserved populations.
- Genomic sequencing enabled targeted therapies, such as enzyme replacement for LIPA deficiency.
- The findings underscore the need for global investment in healthcare infrastructure to ensure equitable access to genomic medicine for vulnerable patients.
Abstract:
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.
