Question

Which patients with mutations in phenylalanine hydroxylase are most likely to respond to BH4 supplementation?

A Those with null mutations
B Those who have only one phenylalanine hydroxylase (PAH) mutation
C Those who are compound heterozygotes for PAH mutations
D Those with residual PAH activity
E Those with a defect in BH4-PAH binding

Answer 1

Patients with residual PAH activity are most likely to respond to BH4 supplementation, as some level of enzyme function may be supported with the cofactor. Complete null mutations or specific defects in BH4-PAH binding are less likely to benefit.

Step-by-step explanation:

Patients most likely to respond to BH4 (tetrahydrobiopterin) supplementation are those with residual phenylalanine hydroxylase (PAH) activity. PAH mutations can vary, and BH4 responsiveness tends to be higher in patients with certain types of mutations that allow for some residual enzyme activity. These patients still produce PAH enzymes that are capable of metabolizing phenylalanine when provided sufficient cofactor, which BH4 supplementation provides. However, those with complete null mutations lack enzyme activity and thus are unlikely to benefit from BH4. Additionally, compound heterozygotes may respond if at least one mutation allows for some PAH function. Lastly, defects specifically in BH4-PAH binding would likely not be amenable to BH4 supplementation.