RESUMO
Defects of mitoribosome assembly with destabilization of mitochondrial ribosomal proteins and subsequent aberrant mitochondrial translation machinery are one of the emerging categories of human mitochondrial disease. Mitochondrial translation deficiency constitutes a growing cause of combined oxidative phosphorylation deficiency and overall causes a set of clinically heterogeneous multi-systemic diseases. We present here the sixth individual with combined oxidative phosphorylation deficiency-9 (COXPD9) secondary to a likely pathogenic homozygous MRPL3 variant c.571A > C; p.(Thr191Pro). MRPL3 encodes a large mitochondrial ribosome subunit protein, impairing the mitochondrial translation and resulting in multisystem disease. Similar to previously reported individuals, this reported female proband presented with psychomotor retardation, sensorineural hearing loss, hypertrophic cardiomyopathy, failure to thrive, and lactic acidosis. Further, she has additional, previously unreported, features including Leigh syndrome, cataracts, hypotonia, scoliosis, myopathy, exercise intolerance, childhood-onset cardiomyopathy, and microcephaly. This subject is the oldest reported individual with COXPD9. This report also summarizes the clinical and molecular data of the previously reported individuals with COXPD9 to describe the full phenotypic spectrum.