Successful diagnosis of HIBCH deficiency from exome sequencing and positive retrospective analysis of newborn screening cards in two siblings presenting with Leigh's disease

•Two siblings with HIBCH deficiency identified through exome sequencing•Disease incidence estimates suggest that HIBCH deficiency may be under-diagnosed.•Retrospective analysis of NBS cards found elevated 3-hydroxy-isobutyryl-carnitine•ACMG algorithms could be modified to include HIBCH deficiency for elevated C4-OH.•Acylcarnitines should be included in the work-up of patients with Leigh syndrome.