Genotype–Phenotype Correlations in Chinese Pediatric Patients With Single Large‐Scale Mitochondrial DNA Deletion Disorders

ABSTRACT This study investigated clinical and genetic characteristics of Chinese pediatric patients with single large‐scale mitochondrial DNA deletions (SLSMD). We analyzed 28 patients (July 2004–March 2025) using long‐range PCR and next‐generation sequencing. Spearman correlation and ANOVA assessed genotype–phenotype relationships. Patients (mean age 5.52 ± 3.96 years) exhibited multi‐organ involvement (5.43 ± 1.87 organs). Common initial presentations included ocular (29%), neurologic, and endocrine dysfunction. Only 14.3% had the classic 4977 bp deletion, and 23 novel deletions were identified in 25 patients. Larger deletions correlated with more deleted MRC complexes ( r = 0.516, p = 0.0123) and more deleted tRNAs ( r = 0.534, p = 0.0103). Kearns‐Sayre syndrome (KSS) patients had later onset ( p = 0.0337), larger deletions ( p = 0.0263), and greater tRNA/MRC complex ( p = 0.0263, p = 0.0319) involvement than non‐KSS patients. SLSMD in Chinese children primarily causes KSS, Pearson syndrome (PS), and progressive ophthalmoplegia with multi‐organ involvement. Genotype–phenotype correlations exist, particularly between deletion size, onset age, and disease severity. KSS patients show distinct genetic and clinical profiles, suggesting slower progression. This study expands the known SLSMD spectrum and underscores mitochondrial testing in pediatric multi‐organ disorders.