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.

Expressing breast milk at home for 24-h periods provides viable samples for macronutrient analysis.

AIM: This study aimed to evaluate the reproducibility of macronutrient measurements of domestic pooled human milk from mothers with preterm infants and to see how the results affected human milk fortifications. METHODS: We asked 28 new mothers to express their breast milk for 24 h on two consecutive days and repeat the process at weekly intervals. The samples were analysed using mid-infrared technology to calculate the differences between the milk collected on two consecutive days for reproducibility and the total protein supply with standard fortification. RESULTS: There was a significant linear correlation between the two consecutive days with regard to protein (r = 0.94, p < 0.001), lipids (r = 0.86, p < 0.001), lactose (r = 0.91, p < 0.001) and 24-h volume (r = 0.96, p < 0.001). The percentage of the samples that would provide a protein supply of 3.5-4.5 g/kg/d with a fortification of 0.6 and 1.2 g protein/100 mL at a volume of 170 mL/kg were 28% and 41%, respectively. CONCLUSION: The domestic pooling of 24-h expressed human milk for macronutrient analysis was a simple and reliable way of obtaining representative data. Standard fortification implies there is a risk of under- and over-nutrition, and individual fortification may improve the nutrition of preterm infants.