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Background: Glycogen storage disease type Ib (GSD Ib) is an autosomal recessively inherited deficiency of the glucose-6-phosphate translocase (G6PT). Clinical features include a combination of a metabolic phenotype (fasting hypoglycemia, lactic acidosis, hepatomegaly) and a hematologic phenotype with neutropenia and neutrophil dysfunction. Dietary treatment involves provision of starches such as uncooked cornstarch (UCCS) and Glycosade® to provide prolonged enteral supply of glucose. Granulocyte colony-stimulating factor (G-CSF) is the treatment of choice for neutropenia. Because long-term stimulation of hematopoiesis with G-CSF causes serious complications such as splenomegaly, hypersplenism, and osteopenia; hematopoietic stem cell transplantation (HSCT) has been considered in some patients with GSD Ib to correct neutropenia and avoid G-CSF related adverse effects. Whether HSCT also has an effect on the metabolic phenotype and utilization of carbohydrate sources has not been determined., Objective: Our objective was to measure the utilization of starch in a patient with GSD Ib before and after HSCT using the minimally invasive 13 C-glucose breath test ( 13 C-GBT)., Design: A case of GSD Ib (18y; female) underwent 13 C-GBT four times: UCCS (pre-HSCT), UCCS (3, 5 months post-HSCT) and Glycosade® (6 months post-HSCT) with a dose of 80 g administered via nasogastric tube after a 4 h fast according to our patient's fasting tolerance. Breath samples were collected at baseline and every 30 min for 240 min. Rate of CO 2 production was measured at 120 min using indirect calorimetry. Finger-prick blood glucose was measured using a glucometer hourly to test hypoglycemia (glucose <4 mmol/L). Biochemical and clinical data were obtained from the medical records as a post-hoc chart review., Results: UCCS utilization was significantly higher in GSD Ib pre-HSCT, which reduced and stabilized 5 months post-HSCT. UCCS and Glycosade® utilizations were low and not different at 5 and 6 months post-HSCT. Blood glucose concentrations were not significantly different at any time point., Conclusions: Findings show that HSCT stabilized UCCS utilization, as reflected by lower and stable glucose oxidation. The results also illustrate the application of 13 C-GBT to examine glucose metabolism in response to various carbohydrate sources after other treatment modalities like HSCT in GSD Ib., Competing Interests: None., (© 2023 The Author(s).)

Background: Glycogen storage disease type Ia (GSD Ia) is an autosomal recessive disorder caused by deficiency of glucose-6-phosphatase (G6Pase), resulting in fasting hypoglycemia. Dietary treatment with provision of uncooked cornstarch (UCCS) or a novel modified cornstarch ( Glycosade® ) is available to treat hypoglycemia, yet choice of carbohydrate to achieve a desirable glycemic control is debated. 13 C-glucose breath test ( 13 C-GBT) can be used to examine glucose metabolism from different carbohydrate sources via 13 CO 2 in breath., Objectives: Our objectives were: 1) establishing the use of a minimally invasive 13 C-GBT to examine in vivo glucose metabolism in healthy adults, and 2) using 13 C-GBT to measure utilization of the standard UCCS vs. Glycosade® in GSD Ia and healthy controls., Design: Experiment 1- Ten healthy adults (6F: 4 M, 22-33y) underwent 13 C-GBT protocol twice as a proof-of-principle, once with oral isotope dose (glucose 75 g + [U- 13 C 6 ] d-glucose 75 mg) and once without isotope (only glucose 75 g) to test sensitivity of natural 13 C-enrichment. Breath samples were collected at baseline and every 20 min for 240 min. Rate of CO 2 production was measured at 120 min using indirect calorimetry. Finger-prick blood glucose was measured using a glucometer hourly to test hypoglycemia (glucose <4 mmol/L). Experiment 2- Three GSD Ia (12y, 13y, and 28y) and six healthy controls (2F: 4 M, 10-32y) underwent 13 C-GBT protocol twice: with UCCS or Glycosade® (based on their current prescribed dose 42-100 g) after ~4 h fast based on our GSD Ia patients with fasting tolerance., Results: Findings 1- Maximum 13 C-enrichments occurred at 200 min without and with [U- 13 C 6 ] d-glucose in all healthy adults, suggesting natural enrichment is sensitive for the 13 C-GBT. Findings 2- Glycosade® utilization was lower than UCCS utilization in 12y and 13y GSD Ia, but was similar in the 28y GSD Ia., Conclusions: 13 C-GBT is a novel minimally invasive functional test to examine glucose metabolism in GSD Ia, and test new products like Glycosade® , which has the potential to improve nutritional management and individualized carbohydrate supply in GSD., Competing Interests: None., (© 2022 The Authors.)