Abstract
Hyperglycemia is a rare presenting symptom of mitochondrial disorders. We report a case of a young girl who presented shortly after birth with ketoacidosis, hyperlactatemia, hyperammonemia, and insulin-responsive hyperglycemia. Initial metabolic work-up suggested mitochondrial dysfunction. Given our patient’s unusual presentation, whole-exome sequencing (WES) was performed on the parent–offspring trio. The patient was homozygous for the c.643C>T (p.Leu215Phe) variant in CYC1, a nuclear gene which encodes cytochrome c 1 , a subunit of respiratory chain complex III. Variants in this gene have only been previously reported in two patients with similar presentation, one of whom carries the same variant as our patient who is also of Sri Lankan origin.
Primary complex III deficiencies are rare and its phenotypes can vary significantly, even among patients with the same genotype.
Competing interests: None declared
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Acknowledgements
We gratefully acknowledge the family for their participation in this study; Mrs. X. Han for Sanger sequencing; Mr. B. Sayson and Ms A. Ghani for consenting and data management; and Mrs. M. Higginson for DNA extraction, sample handling, and technical data (University of British Columbia, Vancouver, CA).
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Communicated by: Garry Brown
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Take Home Message
By reading this third case report of a patient with mitochondrial complex III deficiency caused by mutations in the cytochrome C1 gene and the unique way in which she presented, readers will learn the importance of keeping mitochondrial complex III deficiency in their differential diagnosis given the diverse presentation of patients.
Author Contributions
Natascia Anastasio, MD, MSc: Planning and drafting of article
MajaTarailo-Graovac, PhD: Analysis and interpretation of data and article revision and contribution
Reem Al-Khalifah, MD: Article contribution and revision
Laurent Legault, MD: Article revision and contribution
Britt Drogemoller, PhD: Analysis and interpretation of data and article revision and contribution
Colin J.D. Ross, MSc, PhD: Analysis and interpretation of data
Wyeth W Wasserman, PhD: Analysis and interpretation of data
Clara van Karnebeek, MD, PhD: Analysis and interpretation of data and article revision and contribution
Guarantor: Daniela Buhas, MD: Analysis and interpretation of data, planning and drafting of article
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Conflict of Interest
Natascia Anastasio, MajaTarailo-Graovac, Reem Al-Khalifah, Laurent Legault, Britt Drogemoller, Colin J.D. Ross, Wyeth W Wasserman, Clara van Karnebeek, and Daniela Buhas declare no conflict of interest.
Patient Consent
Parents provided informed consent for publication of this case report.
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The authors declare that the experiments comply with the current laws of Canada, the country in which they were performed.
Funding
This work was supported by funding from the B.C. Children’s Hospital Foundation as “1st Collaborative Area of Innovation” (www.tidebc.org), Genome BC (SOF-195 grant), the Canadian Institutes of Health Research (#301221 grant). Informatics infrastructure was supported by Genome BC and Genome Canada (ABC4DE Project). Clara van Karnebeek is recipient of the Michael Smith Foundation for Health Research Scholar Award.
The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.
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Anastasio, N. et al. (2016). Mitochondrial Complex III Deficiency with Ketoacidosis and Hyperglycemia Mimicking Neonatal Diabetes. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 31. JIMD Reports, vol 31. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_557
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DOI: https://doi.org/10.1007/8904_2016_557
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