Clinical and Laboratory ObservationsGlycogen synthase deficiency (glycogen storage disease type 0) presenting with hyperglycemia and glucosuria: Report of three new mutations☆,☆☆
Section snippets
Methods
Patients were admitted to the General Clinical Research Center (GCRC) for biochemical monitoring as outlined by Aynsley-Green et al.1 Hourly measurements of plasma glucose and blood lactate concentrations were performed. After the plasma glucose concentration decreased to <50 mg/dL, glucagon (0.03 mg/kg) was administered intravenously, and plasma glucose and blood lactate concentrations were measured every 15 minutes for 1 hour. Thereafter, patients had a mixed meal with hourly measurements of
Case report 1
A 5-year-old boy was found to have glucosuria on a routine urinalysis in the absence of polyuria, polydipsia, polyphagia, and weight loss. He had normal plasma electrolyte and glucose concentrations and no evidence of acidosis. Because of a family history of type 1 diabetes mellitus, the family was instructed to monitor blood glucose concentrations by using a blood glucose meter and to screen each urine sample for ketones and glucose. Blood glucose monitoring revealed occasional hypoglycemia in
Case report 2
A 9-year-old girl had glucosuria and ketonuria during evaluation of a mild febrile illness. Laboratory evaluation demonstrated normal plasma electrolyte and glucose concentrations without acidosis. Subsequent blood glucose and urine monitoring revealed fasting ketotic hypoglycemia associated with postprandial hyperglycemia. She was growing at the 5th and 10th percentiles, respectively, for height and weight. Her physical examination and laboratory evaluations were otherwise unremarkable. The
Discussion
GSD0 was initially described as a devastating disorder characterized by fasting hypoglycemia, seizures, and severe developmental delay.2 Aynsley-Green et al1 expanded the clinical phenotype to include small for gestatational age, morning drowsiness, lethargy, and growth failure. We describe two asymptomatic children with confirmed GSD0 who had glucosuria and hyperglycemia.
Because of the varied presentation of the disease, it is likely that GSD0 is underdiagnosed. Postprandial hyperglycemia and
Acknowledgements
The authors thank Ms Cindy Georges, Mrs Jennifer Blish, Ms Karen Leafe, the staff of the GCRC, and the technologists in the Endocrinology laboratory for their contributions to the care of the patients.
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Cited by (33)
Novel GYS2 mutations in a Japanese patient with glycogen storage disease type 0a
2021, Molecular Genetics and Metabolism ReportsCitation Excerpt :For example, one patient (patient 17 in Table 1) with compound heterozygous nonsense mutations (p.Arg5Ter in exon 1 and p.Gln183Ter in exon 4) had diagnosed GSD 0a at 5 years old, presenting with glucosuria. He was asymptomatic and had neither mental retardation nor seizures [18]. The other three patients (12, 26, and 27) with the same homozygous mutation (p.Arg246Ter in exon 5) had different phenotypes.
Disorders of Carbohydrate Metabolism
2020, Emery and Rimoin’s Principles and Practice of Medical Genetics and Genomics: Metabolic DisordersInhibition of Glycogen Synthase II with RNAi Prevents Liver Injury in Mouse Models of Glycogen Storage Diseases
2018, Molecular TherapyCitation Excerpt :However, Gys2 silencing has no effect on preventing fasting hypoglycemia (Figure S13). Whereas Gys2-deficient patients (GSD 0) have mild hypoglycemia and liver complications,29–31 hypoglycemia was not exacerbated by Gys2 silencing (Figure S13). Thus, targeting GYS2 could provide a potentially safe therapeutic approach for preventing liver complications, such as HCA and HCC in GSD Ia and III.
Inborn Errors of Metabolism with Hypoglycemia: Glycogen Storage Diseases and Inherited Disorders of Gluconeogenesis
2018, Pediatric Clinics of North AmericaCitation Excerpt :Most children are identified incidentally when ketotic hypoglycemia is documented during a gastrointestinal illness. Postprandial hyperglycemia and fasting ketonuria can be confused as early diabetes, and GSD 0 should be considered in any child with asymptomatic hyperglycemia or glucosuria.64 There is significant clinical variability, and it can present with seizures, growth failure, or hypoglycemia.63
Pediatric patient with hyperketotic hypoglycemia diagnosed with glycogen synthase deficiency due to the novel homozygous mutation in GYS2
2015, Molecular Genetics and Metabolism ReportsCitation Excerpt :Usually hypoglycemia is found in laboratory tests performed during differential diagnosis process [5]. In general, GSD 0 has no impact on physical or mental development, only some children may have a mild growth delay [5]. Alike other hepatic glycogenosis, the goal of management for GSD 0 is to prevent hypoglycemia by avoiding fasting.
Disorders of Carbohydrate Metabolism
2013, Emery and Rimoin's Principles and Practice of Medical Genetics
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Supported by a Clinical Research Center Grant from the Public Health Service Division of Research Resources (National Institutes of Health M01RR02172) and from the Children's Hospital Glycogen Storage Disease Research Fund. Dr Weinstein was supported by the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center—Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer, Inc. B. E. B. and D. A. W. contributed equally to this work.
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Reprint requests: David A. Weinstein, MD, Division of Endocrinology, Childreny's Hospital Boston, 300 Longwood Ave, Boston, MA 02115.