Delineation and Phenotypic Expansion of TOP3A-Related Mitochondrial Disease in Childhood.
Rodrigo T Starosta, Marisa W Friederich, Graeme Preston et al.
✦ AI-curated · Sources linked
Case in brief
The report describes four previously unreported patients with childhood-onset TOP3A-related mitochondrial disease, presenting with developmental delay, sensorineural hearing loss, cardiomyopathy with rhythm abnormalities, and, in some, stroke-like episodes, a Leigh-like phenotype, or epilepsy. Examination of muscle and heart tissue showed mitochondrial dysfunction, combined respiratory-chain complex deficiency, and a mitochondrial DNA maintenance disorder, with disease primarily expressed in the heart. Three patients underwent heart transplantation, which was successful; slowly progressive neurological disease remained a feature.
What made this case unusual
The childhood-onset presentation broadens the recognized TOP3A disease spectrum beyond the infantile Bloom-like and adult-onset ophthalmoplegia, myopathy, and ataxia phenotypes, with prominent cardiac disease and neurological features.
Diagnostic / clinical pearl
Consider TOP3A-related mitochondrial disease in children with cardiomyopathy and rhythm abnormalities accompanied by developmental or neurological features; tissue findings may indicate mitochondrial DNA maintenance dysfunction.
Why it matters
The report describes successful heart transplantation in three affected patients, while noting that neurological disease may continue to progress.