Endocrine Disorders in Primary Mitochondrial Disease

Iman S Al-Gadi; Richard H Haas; Marni J Falk; Amy Goldstein; Shana E McCormack

doi:10.1210/js.2017-00434

Endocrine Disorders in Primary Mitochondrial Disease

J Endocr Soc. 2018 Feb 19;2(4):361-373. doi: 10.1210/js.2017-00434. eCollection 2018 Apr 1.

Authors

Iman S Al-Gadi¹, Richard H Haas^{2

3

4

5}, Marni J Falk^{5

6

7

8}, Amy Goldstein^{5

6

7}, Shana E McCormack^{5

7

8

9}

Affiliations

¹ Department of Pediatrics, University of Illinois at Chicago, Chicago, Illinois.
² Department of Neurosciences, University of California San Diego, La Jolla, California.
³ Department of Pediatrics, University of California San Diego, La Jolla, California.
⁴ Division of Neurosciences, Rady Children's Hospital, San Diego, California.
⁵ North American Mitochondrial Disease Consortium, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
⁶ Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
⁷ Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
⁸ Children's Hospital of Philadelphia Mitochondrial Medicine Frontiers Program, Philadelphia, Pennsylvania.
⁹ Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Abstract

Context: Endocrine disorders are common in individuals with mitochondrial disease. To develop evidence-based screening practices in this high-risk population, updated age-stratified estimates of the prevalence of endocrine conditions are needed.

Objective: To measure the point prevalence of selected endocrine disorders in individuals with mitochondrial disease.

Design setting and patients: The North American Mitochondrial Disease Consortium Patient Registry is a large, prospective, physician-curated cohort study of individuals with mitochondrial disease. Participants (n = 404) are of any age, with a diagnosis of primary mitochondrial disease confirmed by molecular genetic testing.

Main outcome measures: Age-specific prevalence of diabetes mellitus (DM), abnormal growth and sexual maturation (AGSM), hypoparathyroidism, and hypothyroidism.

Results: The majority of our sample was pediatric (<18 years; 60.1%), female (56.9%), and white (85.9%). DM affected 2% of participants aged <18 years [95% confidence interval (CI): 0.4% to 5.7%] and 24.4% of adult participants (95% CI: 18.6% to 30.9%). DM prevalence was highest in individuals with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes syndrome (MELAS; 31.9%, of whom 86.2% had the m.3243A>G mutation). DM occurred more often with mitochondrial DNA defects (point mutations and/or deletions) than with nuclear DNA mutations (23.3% vs 3.7%, respectively; P < 0.001). Other prevalence estimates were 44.1% (95% CI: 38.8% to 49.6%) for AGSM; 0.3% (95% CI: 0% to 1.6%) for hypoparathyroidism; and 6.3% (95% CI: 4% to 9.3%) for hypothyroidism.

Conclusion: DM and AGSM are highly prevalent in primary mitochondrial disease. Certain clinical mitochondrial syndromes (MELAS and Kearns-Sayre/Pearson syndrome spectrum disorders) demonstrated a higher burden of endocrinopathies. Clinical screening practices should reflect the substantial prevalence of endocrine disorders in mitochondrial disease.

Keywords: diabetes mellitus; growth; hypothyroidism; mitochondrial disease.

Abstract

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