Newborn Screening for Glutaric Aciduria-II: The New England Experience.

Sahai I, Garganta CL, Bailey J, James P, Levy HL, Martin M, Neilan E, Phornphutkul C, Sweetser DA, Zytkovicz TH, Eaton RB.

Source

New England Newborn Screening Program, University of Massachusetts Medical School, Jamaica Plain, MA, USA, inderneel.sahai@umassmed.edu.

Abstract

Newborn screening (NBS) using tandem mass spectrometry (MS/MS) permits detection of neonates with Glutaric Aciduria-Type II (GA-II). We report follow-up of positive GA-II screens by the New England Newborn Screening Program.Methods: 1.5 million infants were screened for GA-II (Feb 1999-Dec 2012). Specialist consult was suggested for infants with two or more acylcarnitine elevations suggestive of GA-II.Results: 82 neonates screened positive for GA-II, 21 weighing > 1.5 kg and 61 weighing ≤ 1.5 kg. Seven (one weighing < 1.5 kg), were confirmed with GA-II. Four of these had the severe form (died < 1 week). The other three have a milder form and were identified because of newborn screening. Two (ages > 5 years) have a G-Tube in place, had multiple hospitalizations and are slightly hypotonic. The third infant remains asymptomatic (9 months old). Two GA-II carriers were also identified. The remaining positive screens were classified as false positives (FP). Six infants (> 1.5 kg) classified as FP had limited diagnostic work-up. Characteristics and outcomes of all specimens and neonates with a positive screen were reviewed, and marker profiles of the cases and FP were compared to identify characteristic profiles.Conclusion: In addition to the severe form of GA-II, milder forms of GA-II and some GA-II carriers are identified by newborn screening. Some positive screens classified as FP may be affected with a milder form of the disorder. Characteristic GA-II profiles, quantified as GA-II indexes, may be utilized to predict probability of disorder and direct urgency of intervention for positive screens.