MICOS13-Related Combined Oxidative Phosphorylation Deficiency 37: A Case Report and Systematic Review of the Literature.

BACKGROUND

Mitochondrial Contact Site and Cristae Organizing System (MICOS13)- related combined oxidative phosphorylation deficiency 37 is a rare autosomal recessive disorder caused by disruption of mitochondrial structure and function, leading to early-onset multisystem disease. Case report: A genetically confirmed case is described in a 5-month-old female infant born to consanguineous Iraqi parents, presenting with hypotonia, developmental delay, feeding difficulties, laryngomalacia, and recurrent cyanotic episodes. Clinical findings included diminished reflexes and a small atrial septal defect, while laboratory tests revealed hypoalbuminaemia and mild coagulopathy. Whole-exome sequencing identified a homozygous MICOS13 splice-site variant (c.260-2A >G). Despite supportive care, progressive respiratory failure developed, resulting in death at 5months. Review of 13 reported cases demonstrates consistent early onset, universal hepatic and neurological involvement, frequent respiratory compromise, and, among reported cases, uniformly fatal outcomes. Most identified variants are loss-of-function, predominantly frameshift, with no missense variants reported to date.

CONCLUSION

The present report adds a genetically confirmed case and reinforces the value of considering MICOS13 deficiency in consanguineous infants with early encephalopathy and hepatic dysfunction.