PHYH and Refsum disease: The observation that cellular abundant 2-oxoacids sustain catalysis of pathogenic AspH variants is precedented by work on the 2-oxoacid cosubstrate scope of the Refsum disease–associated R275Q/W PAHX variants (160), corresponding to the R735Q/W variations in AspH (78), revealing their inactivity with 2OG can be partially rescued by hydrophobic amino acid transamination products lacking a 2OG C-5 carboxylate equivalent group (179).