Studies across different cohorts have shown that 2%–10% of patients affected by PPIX accumulation carry gain of function mutations in ALAS2, and that XLEPP is associated with higher blood PPIX concentrations and an increased risk for liver failure as compared to EPP1 (Whatley et al., 2008; Ducamp et al., 2013; Brancaleoni et al., 2016; Balwani et al., 2017; Ventura et al., 2020). Here, ALAS2 is linked to liver failure.