The reader correctly notes that mutations of many genes result in increased plasma levels. By contrast, the mutations of the BCKDH gene in this study affected pathways that led to a decrease in plasma levels of branched chain amino acids, as noted in the article:
"Mice deficient for Bckdk display increased basal activity of the BCKDH complex as well as reduced BCAAs in various tissues (11). We measured plasma BCAAs in our patients and found that each patient with a homozygous mutation showed notably lower levels of plasma BCAAs compared with their healthy relatives and reference ranges (Fig.2D and tables S3 to S5). Declines in BCAAs in affected patients with null mutations were more substantial compared to normal reference ranges than those in patients with missense variants (tables S3 to S5) (12)."