Diabetes, macrocytosis, and skin changes in large-scale mtDNA deletion

Nevena Krnic; Duje Braovac; Maja Vinkovic; Jelena Petrinovic Doresic; Katja Dumic Kubat

doi:10.1515/jpem-2025-0016

Article

Diabetes, macrocytosis, and skin changes in large-scale mtDNA deletion

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Published/Copyright: March 10, 2025

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 6

Abstract

Objectives

To present a patient diagnosed with single, large-scale mitochondrial DNA (mtDNA) deletion (SLSMD), a rare and progressive multisystem disorder. Diverse initial symptoms, evolving and overlapping phenotypes, along with genetic heterogeneity present significant challenges for diagnosis.

Case presentation

A 3.2-year-old girl presented with seronegative insulin-dependent diabetes, short stature, skin pigmentation anomalies, and macrocytic anemia. The anemia resolved spontaneously, but the macrocytosis persisted. Over time, diagnosis of corneal dystrophy and sensorineural hearing loss were established. Although no classical biochemical features of mitochondrial disease were present, comprehensive molecular mtDNA analysis was performed from peripheral blood. The results revealed a single mtDNA deletion of 7.423 bp, with 37 % of heteroplasmy, confirming the diagnosis of SLSMDs.

Conclusions

The occurrence of diabetes mellitus as presenting endocrine manifestation of SLSMDs at an early age is uncommon. Macrocytosis, as well as hair and skin pigmentation changes, may be the early indicators of mitochondrial diseases. A cluster of symptoms including antibody-negative diabetes, short stature, and signs of sporadic dysfunction of organs with high energy demand, suggest a distinct pattern commonly observed in mitochondrial disorders.

Keywords: SLSMD; mitochondrial diabetes; macrocytosis; skin pigmentation disorder

Corresponding author: Duje Braovac, MD, Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University Hospital Centre Zagreb, Kispaticeva 12, 10 000, Zagreb, Croatia, E-mail: dbraovac@gmail.com

Research ethics: Not applicable.
Informed consent: Informed consent was obtained from legal guardians of the patient.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: None declared.
Data availability: Not applicable.

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Received: 2025-01-07

Accepted: 2025-02-18

Published Online: 2025-03-10

Published in Print: 2025-06-26

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Articles in the same Issue

https://doi.org/10.1515/jpem-2025-0016

Keywords for this article

SLSMD; mitochondrial diabetes; macrocytosis; skin pigmentation disorder