Endocrine features of primary mitochondrial diseases

Abstract

Purpose of review: Primary mitochondrial diseases are one of the most prevalent groups of multisystem genetic disorders. Endocrinopathies associated with mitochondrial diseases may have clinical features that are distinct from the more common forms. We provide an overview of mitochondrial disorder genetics and phenotypes, focusing on recent studies regarding identification and treatment of associated endocrinopathies.

Recent findings: Known endocrine phenotypes of mitochondrial disorders continue to expand, and now include growth hormone deficiency, hypogonadism, precocious puberty, hypoparathyroidism, hypo- and hyperthyroidism, diabetes, and adrenal insufficiency. Recent studies suggest several genotype-phenotype correlations, including those related to nuclear variants. Diagnosis is important, as special considerations should be made in the management of endocrinopathies in mitochondrial patients. Finally, new mitochondrial replacement strategies may soon be available for women interested in preventing mitochondrial disease transmission to offspring.

Summary: Patients with multiple endocrinopathies or atypical endocrinopathies should be evaluated for primary mitochondrial disease, as a diagnosis may impact management of these individuals.

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FIGURE 1

Mitochondrial disease genetics and phenotypes. Random distribution of mitochondria during cell division results in heteroplasmy, in which only a proportion of mitochondrial gene copies carry a mutation. Once heteroplasmy passes an ill-defined threshold in an individual, mitochondrial disease phenotypes are exhibited. For mitochondrial nuclear gene variants, biallelic pathogenic variants are usually required for disease expression. Adapted from ‘Heteroplasmy’, by BioRender.com (2023). Retrieved from https://app.biorender.com/biorender-templates.

FIGURE 2

Endocrinopathies in primary mitochondrial disease. Endocrinopathies in mitochondrial disorders can affect primary or secondary endocrine organs. Underlying molecular mechanisms remain unclear. Adapted from ‘Primary and Secondary Endocrine Organs’, by BioRender.com (2023). Retrieved from https://app.biorender.com/biorender-templates.