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Application of novel techniques to devise nutritional therapies in patients with glycogen storage disease type I and phenylketonuria Turki, Abrar Mohammed

Abstract

Background: Glycogen storage disease type I (GSD I) is caused by deficiencies in glucose-6-phosphatase/transporter complexes, resulting in fasting hypoglycemia. A novel cornstarch (Glycosade®) is available to treat hypoglycemia, yet choice of carbohydrate to achieve desirable glycemic control is debated. Phenylketonuria (PKU) is caused by phenylalanine hydroxylase deficiency. Treatment is primarily phenylalanine restriction. A new formula, (PKU sphere™) with glycomacropeptide (GMP) and low phenylalanine is available, yet untested for optimal protein synthesis. Objectives: (1) Establishing the use of 13C-glucose breath test (13C-GBT) to examine in vivo glucose metabolism in healthy adults, (2) Using 13C-GBT measure utilization of the standard, uncooked cornstarch (UCCS) vs. Glycosade® in GSD Ia, (3) Using 13C-GBT measure utilization of UCCS and Glycosade® in GSD Ib, before and after hematopoietic stem cell transplantation (HSCT), and (4) Using L-[1-13C]-lysine (indicator amino acid oxidation, IAAO) to determine whole body protein synthesis with GMP vs. standard L-amino acid in PKU. Methods: (1) Ten healthy adults underwent 13C-GBT protocol twice: with [U-13C6] D-glucose and without isotope to test sensitivity of natural 13C-enrichment. (2) Three GSD Ia (12y, 13y, 28y) and six healthy controls underwent 13C-GBT twice: with UCCS or Glycosade®. (3) A case of GSD Ib underwent 13C-GBT protocol once pre-HSCT and 3 times post-HSCT. (4) Five PKU adults were studied using IAAO protocol for protein synthesis with multiple intakes of GMP vs. standard L-amino acid. Results: (1) 13C-GBT protocol was sensitive with maximum enrichments at 200 min without and with [U-13C6] D-glucose. (2) Glycosade® utilization was lower than UCCS utilization in 12y and 13y GSD Ia, but was similar in the 28y GSD Ia. (3) Glucose oxidation from UCCS was higher in GSD Ib pre-HSCT, which reduced and stabilized 5 months post-HSCT. (4) Whole body protein synthesis responded similarly with increasing intakes of GMP or standard L-amino acid, resulting in high protein bioavailability (99.98%) in GMP. Conclusion: Findings show that 13C-GBT test is a novel functional test to examine glucose metabolism in GSD I, and test new formulas like Glycosade®. In PKU adults, the IAAO method showed for the first time, bioavailability of GMP is high and optimal for protein synthesis.

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