PARS2 and Alpers syndrome: PARS2 was previously implicated in a mitochondrial phenotype featuring neurodegeneration and liver involvement (Alpers syndrome) based on compound heterozygous pathogenic variants.22–24 Interestingly, in one family we show that homozygosity for a variant in PARS2 (NM_152268.3:c.283G>A:p.[Val95Ile]), previously reported only in trans with another allele, fully segregated with global developmental delay, epilepsy, and brain atrophy but without lactic acidosis or renal or liver involvement (Fig. 2).