Appropriateness of Newborn Screening for Alpha-1 Antitrypsin Deficiency; Analysis and Recommendations from a Workshop.

Teckman J, Pardee E, Howell RR, Mannino D, Sharp RR, Brantly M, Wanner A, Lamson J.

Source

*Department of Pediatrics and Biochemistry and Molecular Biology, Saint Louis University School of Medicine and Cardinal Glennon Children's Medical Center. †Washington, DC, and Alpha-1 Foundation, Miami, FL ‡University of Miami, Miller School of Medicine, and National Institutes of Health §University of Kentucky, Lexington, KY ||Cleveland Clinic Foundation, Cleveland, OH ¶University of Florida College of Medicine, Gainesville, FL #University of Miami, Miller School of Medicine, and Alpha-1 Foundation **Alpha-1 Foundation, Miami, FL.

Abstract

OBJECTIVE::

The Alpha-1 Foundation convened a workshop to consider the appropriateness of newborn screening for alpha-1-antitrypsin deficiency.

METHODS::

A review of natural history and technical data was conducted.

RESULTS::

Homozygous ZZ Alpha-1 Antitrypsin (AAT) Deficiency is a common genetic disease occurring in 1 in 2,000-3,500 births. However, it is under recognized and most patients are undiagnosed. AAT deficiency can cause chronic liver disease, cirrhosis and liver failure in children and adults, and lung disease in adults. The clinical course is highly variable. Some neonates present with cholestatic hepatitis and some children require liver transplantation, but many patients remain well into adulthood. Some adults develop emphysema. There is no treatment for AAT liver disease, other than supportive care and liver transplant. There are no data on the effect of early diagnosis on liver disease. Avoidance of smoking is of proven benefit to reduce future lung disease, as is protein replacement therapy. Justifying newborn screening with the aim of reducing smoking and reducing adult lung disease years in the future would be a significant paradigm shift for the screening field. Recent passage of the "GINA" genetic non-discrimination act, and the Affordable Care Act may have a major impact on reducing psychosocial and financial risks of newborn screening, since many asymptomatic children would be identified. Data on the risk benefit ratio of screening in the new legal climate is lacking.