Kennaway et al. (1990) reported a female infant, born of healthy nonconsanguineous Caucasian parents, who presented shortly after birth with hypotonia, lactic acidosis, and seizures. Echocardiogram on day 6 showed no ventricular enlargement, but she died on day ... Kennaway et al. (1990) reported a female infant, born of healthy nonconsanguineous Caucasian parents, who presented shortly after birth with hypotonia, lactic acidosis, and seizures. Echocardiogram on day 6 showed no ventricular enlargement, but she died on day 24 secondary to massive biventricular hypertrophic cardiomyopathy. At autopsy, electron microscopy of cardiac muscle showed displacement of myofibrils by greatly increased numbers of mitochondria, many of which had abnormal shapes and abnormally arranged cristae. Cytochrome c oxidase activity was severely reduced in heart and was in the low-normal range in muscle; it was also diminished in liver and kidney, to 25% of that of controls. Kennaway et al. (1990) noted that in contrast to previously reported patients with COX deficiency, cardiac involvement predominated in this patient, with marked deficiency of COX subunits II, III, VIa, VIb, VIc, and VIIa and relative sparing of subunits IV and Va in cardiac tissue, and only a mild generalized deficiency of COX subunits in skeletal muscle. Alfadhel et al. (2011) described a microcephalic infant girl born with respiratory distress requiring ventilatory support, who was found to be encephalopathic with persistent lactic acidosis. The patient was neurologically depressed with abnormal posturing, central hypotonia, limb spasticity, and absence of primitive reflexes. Brain MRI revealed only subtle changes, with no definite myelination in the posterior limbs of the internal capsule and simpler sylvian fissures than expected for age. Echocardiography showed marked hypertrophy of all cardiac walls with reduced ejection fraction. On day 9 of life, the baby continued to be encephalopathic with reduced motor activity and respiratory depression, and died 20 minutes after extubation. Postmortem skeletal muscle biopsy revealed a subtle decrease in complex IV activity, whereas marked complex IV deficiency was found in cardiac muscle; activity of other respiratory chain complexes was unremarkable. Histopathology showed marked biventricular hypertrophy in the heart, with glycogen deposition and deficiency of COX staining; in addition, there was increased intermyofibrillar and subsarcolemmal glycogen in skeletal muscle, steatosis in the liver, and gliosis in the brain.
In a female infant who died at day 24 of life with hypotonia, lactic acidosis, and massive biventricular cardiac hypertrophy, who was originally reported by Kennaway et al. (1990), Antonicka et al. (2003) identified compound heterozygosity for a ... In a female infant who died at day 24 of life with hypotonia, lactic acidosis, and massive biventricular cardiac hypertrophy, who was originally reported by Kennaway et al. (1990), Antonicka et al. (2003) identified compound heterozygosity for a missense (R217W; 603646.0001) and a splice site mutation (603646.0002) in the COX15 gene. In an infant girl with isolated complex IV deficiency that was more marked in cardiac than skeletal muscle, who died at day 9 of life with encephalopathy, respiratory depression, and marked cardiac hypertrophy of all walls, Alfadhel et al. (2011) analyzed 6 candidate genes and identified compound heterozygosity for the R217W missense mutation and a nonsense mutation (S151X; 603646.0003) in the COX15 gene.