Expanding the Phenotype of TUFM ‐ Related Combined Oxidative Phosphorylation Deficiency 4

Combined oxidative phosphorylation deficiency 4 (COXPD4) is a rare mitochondrial condition caused by biallelic deleterious variants in the nuclear-encoded gene TUFM. To date, most individuals with COXPD4 have presented with encephalopathy, hypotonia, and abnormal brain imaging. Many of the reported individuals died in infancy. We aim to expand the clinical and biochemical phenotype of COXPD4 by reporting on an adult with this condition. Our proband has a homozygous TUFM c.1025T>G, p.(Val342Gly) variant. He has sensorineural hearing loss, hyperlactatemia with mild illness, and reduced activity in mitochondrial complexes I, III, and IV on endomyocardial biopsy. He presents with hypertrophic cardiomyopathy and chronic kidney failure, which have not previously been reported in this condition. Our findings suggest not all individuals with COXPD4 present with significant neurological involvement and highlight the importance of considering COXPD4 as part of the differential diagnosis of hypertrophic cardiomyopathy.