Developmental and Phenotypic Outcomes in Mild Phenylalanine Hydroxylase Deficiency

Area of Science:

• Metabolic disorders
• Newborn screening
• Neurodevelopmental outcomes

Background:

• Benign hyperphenylalaninemia (bHPA) is characterized by elevated phenylalanine (Phe) levels ≤ 360 μmol/L without medical intervention.
• Some individuals with bHPA may experience a rise in Phe levels above 360 μmol/L, presenting a mild phenylketonuria (PKU) phenotype.
• This progression necessitates therapeutic intervention to prevent potential neurocognitive complications.

Purpose of the Study:

• To identify risk factors associated with elevated Phe levels (> 360 μmol/L) in individuals initially diagnosed with bHPA.
• To evaluate the long-term outcomes for individuals with bHPA, particularly those whose Phe levels increase over time.
• To understand the association between bHPA, Phe level elevation, and neurodevelopmental trajectories.

Main Methods:

• Retrospective chart review of 34 individuals diagnosed with bHPA at a single center.
• Categorization of participants into "Risers" (Phe > 360 μmol/L) and "Non-Risers" (Phe ≤ 360 μmol/L).
• Analysis of initial newborn screening (NBS) Phe levels and clinical assessments for developmental and behavioral issues.

Main Results:

• Twelve out of 34 individuals were classified as "Risers".
• The "Risers" group exhibited higher mean Phe levels on their initial newborn screen compared to "Non-Risers".
• Two-thirds of "Risers" showed developmental or behavioral issues, while all "Non-Risers" had typical development.

Conclusions:

• bHPA may carry an increased risk for neurodevelopmental complications, especially in individuals whose Phe levels rise above 360 μmol/L.
• Elevated initial NBS Phe levels may be a predictor for later Phe level increases in bHPA.
• Continuous monitoring of Phe levels and developmental status is essential for individuals with bHPA to detect and manage potential complications early.