Mitochondrial Trifunctional Protein Deficiency: Severe Cardiomyopathy and Cardiac Transplantation

Abstract

We describe mitochondrial trifunctional protein deficiency (MTPD) in two male siblings who presented with severe cardiomyopathy in infancy. The first sibling presented in severe cardiac failure at 6 months of age and succumbed soon after. The second sibling came to attention after newborn screening identified a possible fatty acid oxidation defect. Dietary therapy and carnitine supplementation commenced in the neonatal period. Despite this the second child required cardiac transplantation at 3 years of age after a sudden and rapid decline in cardiac function. The outcome has been excellent, with no apparent extra-cardiac manifestations of a fatty acid oxidation disorder at the age of 7. Pathogenic HADHA mutations were subsequently identified via genome wide exome sequencing. This is the first reported case of MTPD to undergo cardiac transplantation. We suggest that cardiac transplantation could be considered in the treatment of cardiomyopathy in MTPD.Mol Genet Metab. 2011 Aug;103(4):341-8. (PMID: 21549624); J Pediatr. 2003 Jun;142(6):684-9. (PMID: 12838198); Biosci Rep. 2016 Feb 02;36(2):null. (PMID: 26839416); Intern Med J. 2014 Dec;44(12a):1223-31. (PMID: 25169621); Mol Genet Metab. 2015 Sep-Oct;116(1-2):53-60. (PMID: 26116311); Curr Opin Cardiol. 2017 Jan;32(1):69-77. (PMID: 27801690); Mol Genet Metab. 2011 Dec;104(4):556-9. (PMID: 22000755); J Inherit Metab Dis. 2010 Oct;33(5):469-77. (PMID: 20195903); Mol Genet Metab. 2008 Aug;94(4):428-30. (PMID: 18485779); Orphanet J Rare Dis. 2015 Feb 22;10:21. (PMID: 25888220); Hum Mutat. 2015 Feb;36(2):232-9. (PMID: 25393721); Anal Biochem. 1990 May 1;186(2):280-4. (PMID: 2363500); Semin Fetal Neonatal Med. 2011 Aug;16(4):216-21. (PMID: 21606011); Pediatrics. 2002 Jan;109(1):99-104. (PMID: 11773547); Mol Genet Metab. 2005 Jun;85(2):108-14. (PMID: 15896654); J Biol Chem. 1992 Jan 15;267(2):1034-41. (PMID: 1730633); Genomics. 1996 Oct 1;37(1):141-3. (PMID: 8921383); Clin Exp Pharmacol Physiol. 2002 Apr;29(4):339-45. (PMID: 11985547); Cardiol Young. 2016 Jun;26(5):851-9. (PMID: 26979140); J Inherit Metab Dis. 2014 Jan;37(1):137-9. (PMID: 23807318); Pathol Int. 2003 Nov;53(11):775-9. (PMID: 14629302); Hum Mol Genet. 2014 Mar 1;23(5):1311-9. (PMID: 24158852); J Bioenerg Biomembr. 2013 Feb;45(1-2):47-57. (PMID: 23065309); J Biol Chem. 2010 Sep 24;285(39):29834-41. (PMID: 20663895); Neuromuscul Disord. 1996 Oct;6(5):327-37. (PMID: 8938697); Eur J Pediatr. 2000 Apr;159(4):243-6. (PMID: 10789927); J Pediatr. 2007 Apr;150(4):407-11. (PMID: 17382120); Biochem Biophys Res Commun. 1994 Mar 15;199(2):818-25. (PMID: 8135828); Eur J Pediatr. 2015 Dec;174(12):1689-92. (PMID: 26070998); J Biol Chem. 1984 Dec 25;259(24):15040-5. (PMID: 6439716). Linking ISSN: 21928304. Subset: PubMed not MEDLINE; Date of Electronic Publication: 2017 Nov 10. Current Imprints: Publication: 2019- : [Hoboken, NJ] : Wiley; Original Imprints: Publication: Berlin : SSIEM and Springer-Verlag, c2011. <br />