Exome sequencing reveals a homozygous mutation in TWINKLE as the cause of multisystemic failure including renal tubulopathy in three siblings

► Mitochondrial DNA depletion syndrome can cause multisystem involvement. ► Exome sequencing is a powerful tool to detect underlying genetic basis. ► The feature of renal tubulopathy adds to the multisystemic presentation. ► The absence of an epileptic encephalopathy can occur in Twinkle mutations. ► Genetic counselling is of prime importance.