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Genetics of Mitochondrial Cardiomyopathy

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Abstract

Purpose of Review

Primary mitochondrial disorders (PMD) are a heterogeneous group of individual genetic multi-systemic diseases that are challenging to diagnose and manage; currently, there is no cure or FDA-approved therapies for these progressive genetic syndromes. Among the many organs that may be affected by mitochondrial disorders, the heart is one of the most common, given its high energy requirements, leading to mitochondrial cardiomyopathies.

Recent Findings

Mitochondrial cardiomyopathies are due to underlying genetic defects in genes involved in mitochondrial functioning. These genes, which can be of nuclear or mitochondrial DNA, are either directly involved in the electron transport chain and oxidative phosphorylation or play a role in other mitochondrial pathways such as mitochondrial DNA (mtDNA) replication or maintenance of the inner mitochondrial membrane. Due to the high degree of variability and complexity, current therapeutic strategies are inadequately effective in treating mitochondrial cardiomyopathies. Further research, including longitudinal prospective natural history studies and large-scale randomized clinical trials, is warranted to determine the most effective therapeutic and pharmacologic strategies to address mitochondrial cardiomyopathies.

Summary

In this review, we present our current understanding of mitochondrial cardiomyopathies, diagnostic tools, and management.

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Authors and Affiliations

  1. Combined Internal Medicine-Pediatrics Residency Program, University of Pittsburgh Medical Centre, Pittsburgh, PA, USA

    Atif Towheed

  2. Mitochondrial Medicine Frontier Program, Children’s Hospital of Philadelphia, 3500 Civic Center Blvd, Clinical HUB 12Th Floor, Philadelphia, PA, 19104, USA

    Amy C. Goldstein

  3. University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Amy C. Goldstein

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  1. Atif Towheed
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A. T. and A. C. G. wrote and edited the manuscript.

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Correspondence to Amy C. Goldstein.

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Ethics Statement

A retrospective chart review of the clinical course and laboratory test results was performed for patients presented. Informed consent was provided, and all patients were enrolled in the Children’s Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) approved study #08–6177 (Marni J. Falk, PI) that allows for medical record reviews, medical photography, publication for educational purposes, and clinical cohort analyses.

Conflict of Interest

Dr Atif Towheed declares no conflict of interest. Dr Amy Goldstein is a consultant for Reneo Pharmaceuticals and on the Speakers Bureau for United Mitochondrial Disease Foundation and MitoAction.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Towheed, A., Goldstein, A.C. Genetics of Mitochondrial Cardiomyopathy. Curr Cardiovasc Risk Rep 17, 49–72 (2023). https://doi.org/10.1007/s12170-023-00715-4

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