Early diagnosis of Pearson syndrome in neonatal intensive care following rapid mitochondrial genome sequencing in tandem with exome sequencing.
Open accessAbstract
Rapid genomic testing is a valuable new diagnostic tool for acutely unwell infants, however exome sequencing does not deliver clinical-grade mitochondrial genome sequencing and may fail to diagnose mitochondrial disorders caused by mitochondrial DNA (mtDNA) variants. Rapid mitochondrial genome sequencing and analysis are not routinely available in rapid genomic diagnosis programmes. We present two critically ill neonates with transfusion-dependent anaemia and persistent lactic acidosis who underwent rapid mitochondrial genome sequencing in tandem with exome sequencing as part of an exome sequencing-based rapid genomic diagnosis programme. No diagnostic variants were identified on examination of the nuclear exome data for either infant. Mitochondrial genome sequencing identified a large mtDNA deletion in both infants, diagnosing Pearson syndrome within 74 and 55 h, respectively. Early diagnosis in the third week of life allowed the avoidance of a range of other investigations and appropriate treatment planning. Rapid mitochondrial genome analysis provides additional diagnostic and clinical utility and should be considered as an adjunct to exome sequencing in rapid genomic diagnosis programmes.
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Two diagnoses of Pearson syndrome caused by mitochondrial deletions were obtained through concurrent mitochondrial genome sequencing.
“Two molecular diagnoses of Pearson syndrome due to mitochondrial deletions were achieved through concurrent mitochondrial genome sequencing.17”
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- Authors
- Akesson, L. S., Eggers, S., Love, C. J., Chong, B., Krzesinski, E. I., Brown, N. J., Tan, T. Y., Richmond, C. M., Thorburn, D. R., Christodoulou, J., Hunter, M. F., Lunke, S., & Stark, Z.
- Affiliations
- The University of Melbourne (AU)
- Victorian Clinical Genetics Services (AU)
- Monash Medical Centre (AU)
- Corresponding author
- Stark, Zornitza
- ORCID
- Venue
- European Journal of Human Genetics
- Published
- 2019-07-29
- Volume
- 27
- Issue
- 12
- Pages
- 1821-1826
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- PMC
- PMC6871088
- OpenAlex
- W2966491844
- Cited by
- 28
- References
- 31
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 11 · 2020: 2
- FWCI
- 2.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Griffith Research Online (submittedVersion, other-oa)
- Funders
- Department of Health | National Health and Medical Research Council (GNT1113531)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- Pearson syndrome, mitochondrial DNA deletions, exome sequencing, neonatal intensive care, transfusion-dependent anemia, lactic acidosis, mitochondrial disease, critically ill neonates
- MeSH terms
- Whole Genome Sequencing, Exome Sequencing, Congenital Bone Marrow Failure Syndromes, DNA, Mitochondrial, Female, Genetic Testing, Humans, Infant, Newborn, Lipid Metabolism, Inborn Errors, Male, Mitochondria, Muscular Diseases, Intensive Care, Neonatal, Mitochondrial Diseases, Early Diagnosis, Acyl-CoA Dehydrogenase, Long-Chain, Genome, Mitochondrial, Exome
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