Cardiac phenotype in adolescents and young adults with long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency

Gabriela Elizondo; Ajesh Saini; Cesar Gonzalez de Alba; Ashley Gregor; Cary O Harding; Melanie B Gillingham; Jeffrey M Vinocur

doi:10.1016/j.gim.2024.101123

Cardiac phenotype in adolescents and young adults with long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency

Genet Med. 2024 Mar 16;26(6):101123. doi: 10.1016/j.gim.2024.101123. Online ahead of print.

Authors

Gabriela Elizondo¹, Ajesh Saini², Cesar Gonzalez de Alba³, Ashley Gregor¹, Cary O Harding¹, Melanie B Gillingham⁴, Jeffrey M Vinocur⁵

Affiliations

¹ Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR.
² Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR; Portland State University, Urban Honors College, Portland, OR.
³ Department of Pediatric Cardiology, Oregon Health and Science University, Portland, OR.
⁴ Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR. Electronic address: gillingm@ohsu.edu.
⁵ Division of Pediatric Cardiology, Yale University School of Medicine, New Haven, CT.

PMID: 38501492
DOI: 10.1016/j.gim.2024.101123

Abstract

Purpose: Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (LCHADD) is a rare fatty acid oxidation disorder characterized by recurrent episodes of metabolic decompensation and rhabdomyolysis, as well as retinopathy, peripheral neuropathy, and cardiac involvement, such as infantile dilated cardiomyopathy. Because LCHADD patients are surviving longer, we sought to characterize LCHADD-associated major cardiac involvement in adolescence and young adulthood.

Methods: A retrospective cohort of 16 adolescent and young adult participants with LCHADD was reviewed for cardiac phenotype.

Results: Major cardiac involvement occurred in 9 of 16 participants, including sudden death, out-of-hospital cardiac arrest, acute cardiac decompensations with heart failure and/or in-hospital cardiac arrest, end-stage dilated cardiomyopathy, and moderate restrictive cardiomyopathy. Sudden cardiac arrest was more common in males and those with a history of infant cardiomyopathy.

Conclusion: The cardiac manifestations of LCHADD in adolescence and early adulthood are complex and distinct from the phenotype seen in infancy. Life-threatening arrhythmia occurs at substantial rates in LCHADD, often in the absence of metabolic decompensation or rhabdomyolysis. The potential risk factors identified here-male sex and history of infant cardiomyopathy-may hint at strategies for risk stratification and possibly the prevention of these events.

Keywords: Cardiomyopathy; Fatty acid oxidation disorder; Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency; Sudden cardiac arrest; Sudden cardiac death.