Urine glucose tetrasaccharide: A good biomarker for glycogenoses type II and III? A study of the French cohort

Piraud, Monique; Pettazzoni, Magali; Antonio, Marie De; Vianey‐Saban, Christine; Froissart, Roseline; Chabrol, B.; Young, Sarah P.; Laforêt, Pascal

doi:10.1016/j.ymgmr.2020.100583

Cited by 19 publications

(25 citation statements)

References 38 publications

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“…This biomarker has been found to be sensitive but it is not specific to Pompe disease, as it is also elevated in liver abnormalities or in response to food intake. In borderline cases, it might help to establish the diagnosis [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Enzymatic diagnosis of Pompe disease: lessons from 28 years of experience

et al. 2020

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Pompe disease is a lysosomal and neuromuscular disorder caused by deficiency of acid alpha-glucosidase (GAA), and causes classic infantile, childhood onset, or adulthood onset phenotypes. The biochemical diagnosis is based on GAA activity assays in dried blood spots, leukocytes, or fibroblasts. Diagnosis can be complicated by the existence of pseudodeficiencies, i.e., GAA variants that lower GAA activity but do not cause Pompe disease. A large-scale comparison between these assays for patient samples, including exceptions and borderline cases, along with clinical diagnoses has not been reported so far. Here we analyzed GAA activity in a total of 1709 diagnostic cases over the past 28 years using a total of 2591 analyses and we confirmed the clinical diagnosis in 174 patients. We compared the following assays: leukocytes using glycogen or 4MUG as substrate, fibroblasts using 4MUG as substrate, and dried blood spots using 4MUG as substrate. In 794 individuals, two or more assays were performed. We found that phenotypes could only be distinguished using fibroblasts with 4MUG as substrate. Pseudodeficiencies caused by the GAA2 allele could be ruled out using 4MUG rather than glycogen as substrate in leukocytes or fibroblasts. The Asian pseudodeficiency could only be ruled out in fibroblasts using 4MUG as substrate. We conclude that fibroblasts using 4MUG as substrate provides the most reliable assay for biochemical diagnosis and can serve to validate results from leukocytes or dried blood spots.

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Section: Introductionmentioning

confidence: 99%

Enzymatic diagnosis of Pompe disease: lessons from 28 years of experience

et al. 2020

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“…After centrifugation (room temperature (RT), 16,000 x g, 20 min), glucose levels were determined in supernatants of the hydrolysates as well as in seven serially diluted D-glucose standards using a previously reported method (53) performed in the 96-well format exactly as recently described (12). Glycogen content is given as glucose residues per gram fresh weight.…”

Section: Quantification Of Total and Inert Glycogen In Mouse Skeletalmentioning

confidence: 99%

“…The detection of CSF biomarkers in neurodegenerative diseases is common (14). In urine of Pompe disease (GSDII) patients glycogen degradation products have been found abnormally high (15,16). GSD-related changes in brain glycogen, e.g.…”

Section: Introductionmentioning

confidence: 99%

Sensitive quantification of α-glucans in mouse tissues, cell cultures, and human cerebrospinal fluid

Nitschke

Petković

Ahonen

et al. 2020

Journal of Biological Chemistry

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The soluble α-polyglucan glycogen is a central metabolite enabling transient glucose storage to suit cellular energy needs. Glycogen storage diseases (GSDs) comprise over 15 entities caused by generalized or tissue-specific defects in enzymes of glycogen metabolism. In several, e.g. in Lafora disease caused by the absence of the glycogen phosphatase laforin or its interacting partner malin, degradation-resistant abnormally structured insoluble glycogen accumulates. Sensitive quantification methods for soluble and insoluble glycogen are critical to research, including therapeutic studies, in such diseases. This paper establishes methodological advancements relevant to glycogen metabolism investigations generally, and GSDs. Introducing a pre-extraction incubation method, we measure degradation-resistant glycogen in as little as 30 mg skeletal muscle or a single hippocampus from Lafora disease mouse models. The digestion-resistant glycogen correlates with the disease-pathogenic insoluble glycogen and can readily be detected in very young mice where glycogen accumulation has just begun. Secondly, we establish a high-sensitivity glucose assay with detection of ATP depletion, enabling 1) quantification of α-glucans in cell culture using a medium-throughput assay suitable for assessment of candidate glycogen synthesis inhibitors, and 2) discovery of α-glucan material in healthy human cerebrospinal fluid, establishing a novel methodological platform for biomarker analyses in Lafora disease and other GSDs.

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“…The glucose tetrasaccharide, Glcα1‐6Glcα1‐4Glcα1‐4Glc (Glc 4 ) is a glycogen limit dextrin produced by circulatory amylases and neutral α1‐4‐glycosidases 11 . It is elevated in conditions associated with increased glycogen accumulation and/or release of glycogen from damaged tissues 12‐16 . Urinary Glc 4 is an established biomarker in patients with Pompe disease, correlating with skeletal muscle glycogen and disease status in these patients 17‐19 .…”

Section: Introductionmentioning

confidence: 99%

“…Urinary Glc 4 is an established biomarker in patients with Pompe disease, correlating with skeletal muscle glycogen and disease status in these patients 17‐19 . Glc 4 is also elevated in GSD III, 16,20‐23 and has potential as a biomarker in this disorder. Glc 4 is usually measured in randomly collected voids (spot urines) for the convenience of patients and clinical personnel.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Aim 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. Methods 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. 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. 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. Conclusions 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.

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Urine glucose tetrasaccharide: A good biomarker for glycogenoses type II and III? A study of the French cohort

Cited by 19 publications

References 38 publications

Enzymatic diagnosis of Pompe disease: lessons from 28 years of experience

Enzymatic diagnosis of Pompe disease: lessons from 28 years of experience

Sensitive quantification of α-glucans in mouse tissues, cell cultures, and human cerebrospinal fluid

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

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Urine glucose tetrasaccharide: A good biomarker for glycogenoses type II and III? A study of the French cohort

Cited by 19 publications

References 38 publications

Enzymatic diagnosis of Pompe disease: lessons from 28 years of experience

Enzymatic diagnosis of Pompe disease: lessons from 28 years of experience

Sensitive quantification of α-glucans in mouse tissues, cell cultures, and human cerebrospinal fluid

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

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