Phenylalanine hydroxylase deficiency diagnosis and management

Abstract

Purpose: To replace an existing clinical practice guideline for the diagnosis and management of phenylalanine hydroxylase (PAH) deficiency. Methods: The PAH Deficiency Guideline Workgroup used the Grading of Recommendations Assessment, Development, and Evaluation evidence-to-decision framework to develop evidence summaries and practice recommendations based on the recent American College of Medical Genetics and Genomics systematic review. Results: Many recommendations from the 2014 PAH practice guideline are recognized as standard of care in this evidence-based guideline. Key recommendations from the previous guideline that were not supported by strong evidence are now strongly supported; (1) treatment for PAH deficiency should be lifelong for individuals with untreated phenylalanine (Phe) levels > 360 mu mol/L, (2) individuals with lifelong Phe levels <= 360 mu mol/L have better intellectual outcomes than those who do not, (3) achieving Phe levels <= 360 mu mol/L before conception is strongly recommended to prevent pregnancy complications and negative outcomes for the offspring, and (4) genetic testing for PAH variants is recommended at birth to confirm diagnosis and guide therapy. Conclusion: We strongly recommend lifelong maintenance of Phe <= 360 mu mol/L (using plasma or whole blood) for optimal intellectual outcomes and for reduced teratogenicity, utilizing all available and necessary dietary, pharmaceutical, and patient-educational modalities. (c) 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.