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Mol Genet Metab. 2012 Jul;106(3):281-6. doi: 10.1016/j.ymgme.2012.04.013. Epub 2012 Apr 24.

Algorithm for Pompe disease newborn screening: results from the Taiwan screening program.

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1
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.

Abstract

BACKGROUND:

Pompe disease is caused by a deficiency in acid α-glucosidase (GAA) and results in progressive, debilitating, and often life-threatening symptoms. Newborn screening has led to the early diagnosis of Pompe disease, but the best algorithm for screening has not yet been established.

MATERIALS AND METHODS:

GAA and neutral α-glucosidase (NAG) activities in dried blood spots (DBSs) were assayed using 4-methylumbelliferyl-β-d-glucopyranoside as the substrate. We also measure α-galactosidase A (GLA) activity in DBSs for comparison. A total of 473,738 newborns were screened for Pompe disease, and the data were analyzed retrospectively to determine the best screening algorithm.

RESULTS:

The fluorescence assay used in the screening possessed good reproducibility, but the NAG/GAA ratio was superior in separating the true-positive from the false-positive cases. An NAG/GAA cutoff ratio≥60 produces a positive predictive value (PPV) of 63.4%, and in our sample, only two cases of later-onset Pompe disease would have been missed. The GLA/GAA ratio is not as effective as the NAG/GAA ratio.

CONCLUSION:

A suitable control enzyme can improve the performance of newborn screening. Newborn screening for Pompe disease can be performed using the NAG/GAA ratio as a cutoff even in the presence of GAA partial deficiency.

PMID:
22578805
DOI:
10.1016/j.ymgme.2012.04.013
[Indexed for MEDLINE]

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