Papadopoulou et al. (1999) reported 3 unrelated infants with COX deficiency caused by mutation in the SCO2 gene who presented with a fatal infantile cardioencephalomyopathy characterized by hypertrophic cardiomyopathy, lactic acidosis, and gliosis. Heart and skeletal muscle showed ... Papadopoulou et al. (1999) reported 3 unrelated infants with COX deficiency caused by mutation in the SCO2 gene who presented with a fatal infantile cardioencephalomyopathy characterized by hypertrophic cardiomyopathy, lactic acidosis, and gliosis. Heart and skeletal muscle showed reductions in COX activity, whereas liver and fibroblasts had mild COX deficiencies. Histochemistry of muscle from 2 of the patients showed reductions in COX enzyme activity in all fibers, but succinate dehydrogenase (see 6008574) activity appeared normal; there were no ragged-red fibers. Immunohistochemistry showed a severe reduction of the mitochondrially encoded COX I (516030) and II (516040) subunits, whereas the nuclear-encoded COX subunits IV (123864) and Va (603773) were present but reduced in intensity. The authors noted that the clinical phenotype of COX deficiency caused by mutations in the SCO2 gene differed from that caused by mutations in other genes. Jaksch et al. (2000) reported 3 patients from 2 unrelated families who presented at birth with hypotonia, respiratory difficulties, increased blood and CSF lactate, hypertrophic cardiomyopathy, and severely reduced COX activity. All 3 patients died in infancy. Tay et al. (2004) reported a woman whose first pregnancy resulted in spontaneous abortion at 11 weeks' gestation and whose second child died at age 53 days from fatal infantile cardioencephalomyopathy with compound heterozygosity for 2 mutations in the SCO2 gene (604272.0001; 604272.0002; Papadopoulou et al., 1999). Her third pregnancy also resulted in spontaneous abortion at 10 weeks' gestation, and genetic analysis showed that the aborted fetus had the same SCO2 mutations as the second affected child. Tay et al. (2004) noted that SCO2 mutations may be associated with early spontaneous abortions. Verdijk et al. (2008) reported 2 sibs with fatal infantile cardioencephalomyopathy. The proband presented at birth with hypotonia and respiratory insufficiency. He later developed seizures and inspiratory stridor thought to be partly due to brainstem abnormalities. Laboratory studies revealed increased lactate and pyruvate. He died at age 25 days from hypertrophic cardiomyopathy. Chest studies showed progressive hypertrophic cardiomyopathy, and postmortem examination showed cardiomyocyte cytoplasmic vacuolization. Brain imaging showed changes in the periventricular white matter, corticospinal tract, and corpus callosum compatible with mitochondrial disease. COX IV activity was decreased in heart (1% of normal control values), muscle (19%), and cultured fibroblasts (16%). Genetic analysis identified compound heterozygosity for 2 mutations in the SCO2 gene (E140K; 604272.0002 and W36X; 604272.0008). Amniocentesis performed in the second trimester of the second pregnancy identified the same mutations, and the pregnancy was terminated at 23 weeks' gestation. Autopsy showed a female fetus with a grossly enlarged heart and decreased complexity in cerebral gyral pattern indicating antenatal onset of cardiac and brain anomalies.
In 3 unrelated infants with COX deficiency with fatal infantile cardioencephalomyopathy, Papadopoulou et al. (1999) identified compound heterozygous mutations in the SCO2 gene (see, e.g., 604272.0001). In 3 affected patients from 2 families with the disorder, Jaksch et ... In 3 unrelated infants with COX deficiency with fatal infantile cardioencephalomyopathy, Papadopoulou et al. (1999) identified compound heterozygous mutations in the SCO2 gene (see, e.g., 604272.0001). In 3 affected patients from 2 families with the disorder, Jaksch et al. (2000) identified compound heterozygosity for mutations in the SCO2 gene. All 3 patients had an E140K change (604272.0002) on 1 allele (see also 604272.0004 and 604272.0005).