ICNC Abstracts, ICNC 2018

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Fatal neonatal lactic acidosis secondary to a novel defect in COX16 causing complex IV deficiency
Maina Padmanabha Kava, Shanti Balasubramaniam, Barry Lewis, Richard Rodenburg

Last modified: 2018-09-09


A full term male infant of a non-consanguineous Caucasian couple was born to a G7P7 mother. He had symmetrical IUGR, required resuscitation with oxygen and intermittent positive pressure ventilation. Severe lactic acidosis noted at birth (cord pH 7.06, lactate 20 mmol/L and BE -20) persisted despite bicarbonate infusion and THAM. Initial severe hypoglycaemia was corrected. Plasma cortisol, insulin and GH response to hypoglycaemia were appropriate. Creatine kinase was 3000 U/L (NR <450). The baby was then transferred to tertiary care.

He was encephalopathic, extremely floppy, areflexic and dysmorphic. He had multisystemic involvement with liver failure and coagulopathy, moderately dilated and hypertrophic right ventricle and bilateral congenital sensorineural hearing loss. MRI brain showed multiple areas of supratentorial and brainstem infarcts with generalised cerebral edema. Lactate peak was observed on MRS. EEG showed an abnormal background. He remained obtunded and ventilator dependent and succumbed shortly after care was withdrawn at 55 hours.

Microarray, common mtDNA point mutations and POLG1 common mutation testing were negative. Isolated Complex IV deficiency was demonstrated on skeletal muscle and confirmed in fibroblasts. The muscle histology and histochemistry were normal. Whole exome sequencing revealed a homozygous variant in COX16 gene; Chr14(GRCh37): g.70793127G>A; NM_016468.6: c.244C>T p.(Arg82*). The COX16 gene encodes a known assembly factor of complex IV Complementation studies in fibroblasts revealed normalisation of Complex IV activity with wild type COX16 gene.

We describe a novel defect in COX 16 gene causing complex IV deficiency associated with fatal and refractory lactic acidosis.



lactic acidosis, complex IV,COX16

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