Combined Oxidative Phosphorylation Deficiency 3 (TSFM)

Combined oxidative phosphorylation deficiency 3 is a very rare autosomal recessive disorder caused by pathogenic variants in the gene TSFM. While most reported patients have been of various ethnicities, there may be an increased incidence in the Finnish population. Loss of function of the protein encoded by TSFM results in impaired ability of the mitochondria to produce energy for the cell. This disease presents with lactic acidosis, cardiomyopathy, encephalomyopathy, and/or hypotonia, and it is fatal in early infancy. To date, three pathogenic variants have been reported to cause this disease. While too few patients have been reported to determine a genotype-phenotype correlation, it appears that the inheritance of two null alleles may be lethal in early embryonic development.

For information about carrier frequency and residual risk, please see the residual risk table.