Baseline urinary glucose tetrasaccharide concentrations in patients with infantile- and late-onset pompe disease identified by newborn screening
© 2014, SSIEM and Springer-Verlag Berlin Heidelberg. Purpose: The urinary glucose tetrasaccharide, Glcα1-6Glcα1-4Glcα1-4Glc (Glc 4 ), is a biomarker of glycogen accumulation and tissue damage and is elevated in patients with Pompe disease. We report baseline urinary Glc 4 concentrations for patients with classic infantile-onset or late-onset Pompe disease, and those with a pseudodeficiency of acid alpha-glucosidase (GAA), identified through newborn screening (NBS) in Taiwan. Methods: Infants identified through NBS with (1) classic infantile-onset Pompe disease (NBS-IOPD) (n = 7) defined as patients with evidence for hypertrophic cardiomyopathy by EKG, X-ray, and echocardiogram, (2) a late-onset phenotype (NBS-LOPD) (n = 13) defined as patients without evidence for cardiomyopathy, (3) a GAA pseudodeficiency (n = 58), and (4) one patient with LOPD diagnosed in infancy due to family history were consented to the study. Four infants diagnosed after the onset of clinical symptoms (CLIN-IOPD) were included for comparison. Glc 4 concentrations in dried urine samples on filter paper were determined using tandem mass spectrometry. Results: Baseline Glc 4 concentrations were at or above the 90th centile of the age-matched reference range for the NBS-IOPD cohort. The median Glc 4 level for this group was lower than that of the CLIN-IOPD group, although not at the level of significance (p = 0.07), but was significantly higher than that of the NBS-LOPD group (p < 0.05). Baseline Glc 4 was not elevated for the NBS-LOPD and GAA pseudodeficiency cohorts and remained low for late-onset patients that did not require treatment before the age of three years. Conclusion: Baseline urinary Glc 4 is elevated in neonates with infantile-onset Pompe disease identified through NBS.
Chien, YH; Goldstein, JL; Hwu, WL; Smith, PB; Lee, NC; Chiang, SC; Tolun, AA; Zhang, H; Vaisnins, AE; Millington, DS; Kishnani, PS; Young, SP
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