Expanding the Clinical and Genetic Landscape of UQCRC2-related Mitochondrial Complex III Deficiency: A Case Report...

Mitochondrial oxidative phosphorylation (OXPHOS) defects are clinically heterogeneous and often challenging to diagnose. Complex III deficiency caused by UQCRC2 variants is exceptionally rare, with only a limited number of patients described worldwide. Reporting new cases is essential to expand the clinical and molecular landscape of this disorder and to provide insights into potential therapeutic strategies.

We describe a female patient with UQCRC2-related complex III deficiency who experienced recurrent episodes of metabolic decompensation characterized by hypoglycemia, hyperlactatemia, and renal tubular dysfunction from early childhood. Brain magnetic resonance imaging revealed white matter lesions associated with mild neurological symptoms. During metabolic crises, management included intravenous glucose infusion and strict avoidance of prolonged fasting. At age 15, supplementation with coenzyme Q10 was introduced, followed by complete cessation of hospitalizations and a sustained clinical stabilization. Genetic testing identified compound heterozygosity for a known missense variant and a novel frameshift variant in UQCRC2. A literature review of previously reported cases confirmed the broad clinical variability, ranging from severe neonatal presentations to milder phenotypes with survival into adolescence.

This case expands the phenotypic spectrum of UQCRC2-related complex III deficiency and suggests that targeted supplementation with coenzyme Q10 may contribute to improved longterm outcomes. Early recognition of metabolic crises, avoidance of fasting, and genetic confirmation are crucial for diagnosis and management. Further reports are needed to clarify genotype-phenotype correlations and to define the therapeutic role of coenzyme Q10 in this rare mitochondrial disorder.