Mitochondrial DNA Depletion Syndrome 12B: Role of Photon-Counting CT in Detection of Cardiac Involvement—A case report

Abstract Background Mitochondrial DNA depletion syndrome 12B (MDS12B) is an ultra-rare autosomal recessive disorder caused by SLC25A4 mutations, which encode the mitochondrial adenine nucleotide translocator. Hypertrophic cardiomyopathy (HCM) is the predominant manifestation, yet detailed cardiac tissue characterization remains limited. Case summary A 28-year-old male presented with 17-year history of exertional palpitations and progressive fatigue. Echocardiography revealed severe concentric left ventricular hypertrophy with moderately reduced ejection fraction (42%). Photon-counting CT (PCCT) -a novel spectral imaging technique-provided high-resolution coronary anatomy while simultaneously quantifying extracellular volume expansion, late myocardial enhancement, and microvascular obstruction (MVO). Cardiac magnetic resonance (CMR) confirmed these findings. Genetic analysis identified a previously unreported homozygous SLC25A4 frameshift mutation (c.167_170del). Conclusion This case provides the first evidence that PCCT can non-invasively detect both myocardial fibrosis and MVO in MDS12B, offering a potential alternative to CMR when contraindicated or unavailable. The novel frameshift variant expands the genotypic spectrum of SLC25A4-related mitochondrial depletion syndromes.