Diurnal variability of glucose tetrasaccharide (Glc₄) excretion in patients with glycogen storage disease type III

The urinary glucose tetrasaccharide, Glcα1-6Glcα1-4Glcα1-4Glc (Glc₄), 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 Glc₄ monitoring, by measuring the diurnal variability of Glc₄ excretion in patients with GSD III.

Voids were collected at home over 24 hours, stored at 4°C and frozen within 48 hours. Glc₄ was analyzed using liquid chromatography-tandem mass spectrometry and normalized to creatinine.

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. Glc₄ was elevated in 16/18 subjects (median: 13 mmol/mol creatinine, range: 2-75, reference range: <3). In collections with elevated Glc₄ (23/28), two-thirds (15/23) had low diurnal variability in Glc₄ excretion (coefficient of variation [CV%] <25). The diurnal variability was significantly correlated with the Glc₄ 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.

The extent and variability of Glc₄ 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 Glc₄ in patients with GSD III treated with cornstarch. However, repeat sampling over short time-periods will provide the most accurate assessment of Glc₄ excretion, as intraday variability may be increased in patients with high Glc₄ excretion.