Early diagnosis of Pearson syndrome in neonatal intensive care following rapid mitochondrial genome sequencing in tandem with exome sequencing


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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The authors would like to acknowledge the valued and important contributions from clinical and laboratory personnel involved in the care and diagnosis of both patients, in particular Alison Compton, Ksenija Nesic, Dean Phelan, Sarah-Jane Pantaleo, Shannon Cowie, Vanessa Siva Kumar, Zeliha Hizli, Katherine Rose, Michaela Cormack, Arvind Sehgal, Hannah Brogan, Mohan Bagur Krishnamurthy, Radhakrishnan Kottayam, Lyndon Gallacher, Joy Lee, Sarah Donoghue, Sharmila Kiss, Elizabeth Wheeler and Leah Hickey.

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Correspondence to Zornitza Stark.

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The authors declare that they have no conflict of interest.


The Australian Genomics Acute Care study has Human Research Ethics Committee approval (HREC/16/MH251). Following genetic counselling, parents provided informed written consent for rapid genomic testing.

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