Abstract
A patient is reported who presented in the newborn period with an unusual combination of congenital lactic acidosis and bilateral calcifications in the adrenal medulla, visible on standard abdominal x-ray and ultrasound examination. At birth, the proband was hypotonic and dystrophic. She developed respiratory insufficiency, cardiomegaly, and hepatomegaly and died at the age of 38 d. Examination of postmortem heart muscle revealed multiple areas of myocardial infarction with dystrophic calcifications. In the medulla of the adrenal glands, foci of necrosis and calcifications, and in the liver, multiple zones of necrosis and iron deposition were detected. Biochemical analysis in heart muscle revealed a decreased activity of complex IV of the oxidative phosphorylation (OXPHOS) and in liver a combined deficiency involving the complexes I, III, IV, and V. The findings were suggestive of a defect in biosynthesis of the mitochondrially encoded subunits of the OXPHOS complexes. Extensive analysis of the proband's mitochondrial DNA revealed neither pathogenic deletions and point mutations nor copy number alterations. Relative amounts of mitochondrial transcripts for the ribosomal mitochondrial 12S rRNA (12S) and mitochondrial 16S rRNA (16S) were significantly increased suggesting a compensatory mechanism involving the transcription machinery to low levels of translation. The underlying molecular defect has not been identified yet.
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Abbreviations
- 12S:
-
mitochondrial 12S rRNA
- 16S:
-
mitochondrial 16S rRNA
- BN-PAGE:
-
blue native polyacrylamide gel electrophoresis
- COXI:
-
mRNA encoding subunit I of complex IV
- mtDNA:
-
mitochondrial DNA
- OXPHOS:
-
oxidative phosphorylation
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Acknowledgements
We thank Chantal de Groote (Universitaire Instelling Antwerpen) for performing the ultrastructural studies and Mary Phelan for help in correcting the English language.
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Supported by grants from the Fund for Scientific Research (FWO) Belgium, contract grant number G.0666.06 (Universiteit Gent, Vrije Universiteit Brussel), and the Kid-Au-Quai foundation.
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Zecic, A., Smet, J., Praeter, C. et al. Lactic Acidosis in a Newborn With Adrenal Calcifications. Pediatr Res 66, 317–322 (2009). https://doi.org/10.1203/PDR.0b013e3181b40a80
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DOI: https://doi.org/10.1203/PDR.0b013e3181b40a80
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