학술논문
Phenylalanine hydroxylase deficiency treatment and management: A systematic evidence review of the American College of Medical Genetics and Genomics (ACMG).
Document Type
Academic Journal
Author
Adams AD; Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX; Division of Maternal-Fetal Medicine, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.; Fiesco-Roa MÓ; Programa de Maestría y Doctorado en Ciencias Médicas, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico; Laboratorio de Citogenética, Instituto Nacional de Pediatría, Mexico City, Mexico.; Wong L; Southern California Kaiser Permanente, Downey, CA.; Jenkins GP; American College of Medical Genetics and Genomics, Bethesda, MD.; Malinowski J; American College of Medical Genetics and Genomics, Bethesda, MD.; Demarest OM; American College of Medical Genetics and Genomics, Bethesda, MD.; Rothberg PG; Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY.; Hobert JA; University of Utah School of Medicine, Salt Lake City, UT; ARUP Laboratories, Salt Lake City, UT.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 9815831 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-0366 (Electronic) Linking ISSN: 10983600 NLM ISO Abbreviation: Genet Med Subsets: MEDLINE
Subject
Language
English
Abstract
Purpose: Elevated serum phenylalanine (Phe) levels due to biallelic pathogenic variants in phenylalanine hydroxylase (PAH) may cause neurodevelopmental disorders or birth defects from maternal phenylketonuria. New Phe reduction treatments have been approved in the last decade, but uncertainty on the optimal lifespan goal Phe levels for patients with PAH deficiency remains.
Methods: We searched Medline and Embase for evidence of treatment concerning PAH deficiency up to September 28, 2021. Risk of bias was evaluated based on study design. Random-effects meta-analyses were performed to compare IQ, gestational outcomes, and offspring outcomes based on Phe ≤ 360 μmol/L vs > 360 μmol/L and reported as odds ratio and 95% CI. Remaining results were narratively synthesized.
Results: A total of 350 studies were included. Risk of bias was moderate. Lower Phe was consistently associated with better outcomes. Achieving Phe ≤ 360 μmol/L before conception substantially lowered the risk of negative effect to offspring in pregnant individuals (odds ratio = 0.07, 95% CI = 0.04-0.14; P < .0001). Adverse events due to pharmacologic treatment were common, but medication reduced Phe levels, enabling dietary liberalization.
Conclusions: Reduction of Phe levels to ≤360 μmol/L through diet or medication represents effective interventions to treat PAH deficiency.
Competing Interests: Conflict of Interest J.A.H. is associated with a clinical laboratory that performs biochemical genetic, genetic, and genomic analyses on a fee-for-service basis. All other authors declare no conflicts of interest.
(Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)
Methods: We searched Medline and Embase for evidence of treatment concerning PAH deficiency up to September 28, 2021. Risk of bias was evaluated based on study design. Random-effects meta-analyses were performed to compare IQ, gestational outcomes, and offspring outcomes based on Phe ≤ 360 μmol/L vs > 360 μmol/L and reported as odds ratio and 95% CI. Remaining results were narratively synthesized.
Results: A total of 350 studies were included. Risk of bias was moderate. Lower Phe was consistently associated with better outcomes. Achieving Phe ≤ 360 μmol/L before conception substantially lowered the risk of negative effect to offspring in pregnant individuals (odds ratio = 0.07, 95% CI = 0.04-0.14; P < .0001). Adverse events due to pharmacologic treatment were common, but medication reduced Phe levels, enabling dietary liberalization.
Conclusions: Reduction of Phe levels to ≤360 μmol/L through diet or medication represents effective interventions to treat PAH deficiency.
Competing Interests: Conflict of Interest J.A.H. is associated with a clinical laboratory that performs biochemical genetic, genetic, and genomic analyses on a fee-for-service basis. All other authors declare no conflicts of interest.
(Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)