Baseline Urinary Glucose Tetrasaccharide Concentrations in Patients with Infantile- and Late-Onset Pompe Disease Identified by Newborn Screening.

PURPOSE: The urinary glucose tetrasaccharide, Glcα1-6Glcα1-4Glcα1-4Glc (Glc4), is a biomarker of glycogen accumulation and tissue damage and is elevated in patients with Pompe disease. We report baseline urinary Glc4 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. Glc4 concentrations in dried urine samples on filter paper were determined using tandem mass spectrometry. RESULTS: Baseline Glc4 concentrations were at or above the 90th centile of the age-matched reference range for the NBS-IOPD cohort. The median Glc4 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 Glc4 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 Glc4 is elevated in neonates with infantile-onset Pompe disease identified through NBS.

Elevation of guanidinoacetate in newborn dried blood spots and impact of early treatment in GAMT deficiency.

Guanidinoacetate methyltransferase (GAMT) deficiency is a good candidate disorder for newborn screening because early treatment appears to improve outcomes. We report elevation of guanidinoacetate in archived newborn dried blood spots for 3 cases (2 families) of GAMT deficiency compared with an unaffected carrier and controls. We also report a new case of a patient treated from birth with normal developmental outcome at the age of 42 months.