The clinical utility of short-term protein substitute use during intercurrent illness in BH4-responsive phenylketonuria.

OBJECTIVE

Phenylketonuria (PKU) is a metabolic disorder that is primarily treated with dietary phenylalanine (Phe) restriction and/or tetrahydrobiopterin (BH4) therapy. Dietary liberalization is often possible in BH4-responsive PKU patients; however, metabolic control may be impaired during catabolic stress such as illness or fever. The aim of this study was to investigate the efficacy of temporary protein substitution (Phe-free amino acid mixture; PFAAM) during intercurrent illness in BH4-responsive PKU patients managed without dietary protein restriction.

METHODS

This retrospective case series, descriptive study included ten BH4-responsive PKU patients treated with BH4 monotherapy. All patients received PFAAM supplementation exclusively during febrile or disease-related episodes. Clinical, biochemical and genetic data were obtained from medical records. Blood Phe levels were determined before and after PFAAM intake during illness episodes.

RESULTS

All patients experienced a significant increase in blood Phe levels during febrile illnesses despite receiving maximum BH4 dose (20 mg/kg/day). PFAAM supplementation initiated at a median dose of 0.3-1.5 g/kg/day resulted in a rapid decrease in blood Phe levels, often within a few days. In most cases, PFAAM was gradually discontinued once metabolic control was restored, and no patient required long-term dietary Phe restriction. The intervention allowed restoration of metabolic control while maintaining a liberal dietary regimen.

CONCLUSIONS

Temporary PFAAM supplementation during intercurrent illness appears to be an effective adjunct to BH4 therapy to control transient elevations in blood Phe levels. This approach may support metabolic stability without the need for permanent dietary restriction in BH4-responsive PKU patients. Further prospective studies are needed to validate these results in larger cohorts.