Recombinant Adeno-Associated Virus-Based Gene Therapy for Disorders Detected by Newborn Screening: Inherent Limitations of This Approach

UMMS Affiliation

Department of Pediatrics, Division of Pediatric Pulmonology; Gene Therapy Center

Publication Date


Document Type



Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetic Phenomena | Genetics and Genomics | Pediatrics | Therapeutics


For more than 50 years, newborn screening (NBS) in the United States has been used for early detection of potentially lethal single gene disorders, such as phenylketonuria and congenital adrenal hyperplasia.1. Recent clinical successes with recombinant adeno-associated virus (rAAV)–based gene therapy for single gene disorders, such as RPE-65 inherited retinal dystrophy and spinal muscular atrophy, have led investigators and geneticists to consider the possibility of gene therapy for NBS-detected disorders.2 Among the NBS-detected disorders, enzymatic defects leading to failure of synthesis of adrenal cortical steroids, known collectively as congenital adrenal hyperplasia, are among the most significant, in that they can be fatal if untreated, but they can be readily treated with oral corticosteroid replacement if detected promptly. Specifically, in 21-hydroxylase (21-OH) deficiency, deficits in both glucocorticoid and mineralocorticoid functions may lead to hypoglycemia, hyperkalemia, and hyponatremia, any one of which may be life threatening.

DOI of Published Version



Hum Gene Ther. 2018 Apr;29(4):401-402. doi: 10.1089/hum.2018.29064.trf. Link to article on publisher's site

Journal/Book/Conference Title

Human gene therapy

Related Resources

Link to Article in PubMed

PubMed ID