Diurnal variability of glucose tetrasaccharide (Glc 4 ) excretion in patients with glycogen storage disease type III

Aim The urinary glucose tetrasaccharide, Glcα1‐6Glcα1‐4Glcα1‐4Glc (Glc 4 ), is a glycogen limit dextrin that is elevated in patients with glycogen storage disease (GSD) type III. We evaluated the potential of uncooked cornstarch therapy to interfere with Glc 4 monitoring, by measuring the diurnal variability of Glc 4 excretion in patients with GSD III. Methods Voids were collected at home over 24 hours, stored at 4°C and frozen within 48 hours. Glc 4 was analyzed using liquid chromatography‐tandem mass spectrometry and normalized to creatinine. Results Subjects with GSD III (median age: 13.5 years, range: 3.7‐62; n = 18) completed one or more 24‐hour urine collection, and 28/36 collections were accepted for analysis. Glc 4 was elevated in 16/18 subjects (median: 13 mmol/mol creatinine, range: 2‐75, reference range: <3). In collections with elevated Glc 4 (23/28), two‐thirds (15/23) had low diurnal variability in Glc 4 excretion (coefficient of variation [CV%] <25). The diurnal variability was significantly correlated with the Glc 4 concentration (Pearson R = .644, P < .05), but not with the dose of uncooked cornstarch. High intraday variability (>25%) was not consistently observed in repeat collections by the same subject. Conclusions The extent and variability of Glc 4 excretion relative to creatinine was not correlated with cornstarch dose. A majority of collections showed low variability over 24 hours. These findings support the use of single time‐point collections to evaluate Glc 4 in patients with GSD III treated with cornstarch. However, repeat sampling over short time‐periods will provide the most accurate assessment of Glc 4 excretion, as intraday variability may be increased in patients with high Glc 4 excretion.