COXPD9 an Evolving Multisystem Disease; Congenital Lactic Acidosis, Sensorineural Hearing Loss, Hypertrophic Cardiomyopathy, Cirrhosis and Interstitial Nephritis

Abstract

We present the second report of combined oxidative phosphorylation deficiency-9. The infant presented in the neonatal period with poor feeding, lactic acidosis and sensorineural hearing loss. He subsequently developed a lethal hypertrophic cardiomyopathy during infancy. Cirrhosis and interstitial nephritis were identified at autopsy. Exome sequencing has detected compound heterozygous mutations in the MRPL3 gene which encodes a large mitochondrial ribosome subunit protein. We identified a known heterozygous variant NM_007208 c.950>G (Pro317Arg) in the MRPL3 gene and a novel heterozygous mutation NM_007208 c.49delC p.(Arg17Aspfs*57). Mutations in MRPL3 have previously been shown to alter ribosome assembly and cause abnormal function of multiple respiratory chain complexes. Our case adds to the evolving knowledge of disorders of mitochondrial translation.Hum Mol Genet. 2015 Apr 15;24(8):2297-307. (PMID: 25556185); J Med Genet. 2013 Mar;50(3):151-9. (PMID: 23315540); Hum Mutat. 2011 Nov;32(11):1225-31. (PMID: 21786366); Int J Nephrol Renovasc Dis. 2014 Jan 31;7:57-67. (PMID: 24516335); Eur J Hum Genet. 2011 Apr;19(4):394-9. (PMID: 21189481); Pediatr Nephrol. 2012 Apr;27(4):539-50. (PMID: 21656172); Biochim Biophys Acta. 2013 Aug;1832(8):1304-12. (PMID: 23603806); Mol Cell Neurosci. 2013 Jul;55:1-12. (PMID: 22986124); Ann Neurol. 2004 Nov;56(5):734-8. (PMID: 15505824); Neurogenetics. 2015 Oct;16(4):319-23. (PMID: 25797485); Neurogenetics. 2015 Jul;16(3):237-40. (PMID: 25663021). Linking ISSN: 21928304. Subset: PubMed not MEDLINE; Date of Electronic Publication: 2016 Nov 05. Current Imprints: Publication: 2019- : [Hoboken, NJ] : Wiley; Original Imprints: Publication: Berlin : SSIEM and Springer-Verlag, c2011. <br />