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

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.