Title

Phenylalanine Hydroxylase Deficiency Diagnosis and Management

Authoring Organization

Publication Month/Year

December 2, 2024

Last Updated Month/Year

December 10, 2024

Document Type

Guideline

Country of Publication

US

Document Objectives

To replace an existing clinical practice guideline for the diagnosis and management of phenylalanine hydroxylase (PAH) deficiency. 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 μmol/L, (2) individuals with lifelong Phe levels ≤360 μmol/L have better intellectual outcomes than those who do not, (3) achieving Phe levels ≤360 μmol/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. We strongly recommend lifelong maintenance of Phe ≤360 μmol/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.

Inclusion Criteria

Male, Female, Infant

Health Care Settings

Ambulatory, Laboratory services

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Diagnosis, Assessment and screening

Keywords

newborn screening, Pegvaliase

Source Citation

Smith WE, Berry SA, Bloom K, Brown C, Burton BK, Demarest OM, Jenkins GP, Malinowski J, McBride KL, Mroczkowski HJ, Scharfe C, Vockley J; ACMG Board of Directors. Electronic address: documents@acmg.net. Phenylalanine hydroxylase deficiency diagnosis and management: A 2023 evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2024 Dec 2:101289. doi: 10.1016/j.gim.2024.101289. Epub ahead of print. PMID: 39630157.