A novel variant in COX16 causes cytochrome c oxidase deficiency, severe fatal neonatal lactic acidosis, encephalopathy, cardiomyopathy, and liver dysfunction.

COX16 is involved in the biogenesis of cytochrome-c-oxidase (complex IV), the terminal complex of the mitochondrial respiratory chain. We present the first report of two unrelated patients with the homozygous nonsense variant c.244C>T(p. Arg82*) in COX16 with hypertrophic cardiomyopathy, encephalopathy and severe fatal lactic acidosis, and isolated complex IV deficiency. The absence of COX16 protein expression leads to a complete loss of the holo-complex IV, as detected by Western blot in patient fibroblasts. Lentiviral transduction of patient fibroblasts with wild-type COX16 complementary DNA rescued complex IV biosynthesis. We hypothesize that COX16 could play a role in the copper delivery route of the COX2 module as part of the complex IV assembly. Our data provide clear evidence for the pathogenicity of the COX16 variant as a cause for the observed clinical features and the isolated complex IV deficiency in these two patients and that COX16 deficiency is a cause for mitochondrial disease.

Sacral insufficiency fracture after pelvic radiotherapy: a diagnostic challenge for a radiologist.

Sacral insufficiency fractures can occur as a complication after pelvic radiotherapy. Despite several recent studies showing high incidence of sacral insufficiency fractures in elderly women after pelvic radiotherapy this condition still remains underdiagnosed. We present a case of sudden onset of low back pain in a female patient with a history of cervical cancer radiotherapy. Initial diagnostic imaging misinterpreted SIF for metastasis. Bone scan and single-photon emission-computed tomography with low-dose computed tomography revealed the correct diagnosis. Due to the reasons that sacral insufficiency fractures still remain underdiagnosed this report is important to practical routine work of oncologists and radiologists.