Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Oct 27;13(11):3828.
doi: 10.3390/nu13113828.

Glycogen Storage Disease Type Ia: Current Management Options, Burden and Unmet Needs

Terry G J Derks  1 , David F Rodriguez-Buritica  2 , Ayesha Ahmad  3 , Foekje de Boer  1 , María L Couce  4 , Sarah C Grünert  5 , Philippe Labrune  6   7 , Nerea López Maldonado  8   9 , Carolina Fischinger Moura de Souza  10 , Rebecca Riba-Wolman  11 , Alessandro Rossi  1   12 , Heather Saavedra  2 , Rupal Naik Gupta  13 , Vassili Valayannopoulos  13 , John Mitchell  14
Affiliations
Review

Glycogen Storage Disease Type Ia: Current Management Options, Burden and Unmet Needs

Terry G J Derks et al. Nutrients. .

Abstract

Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications. Dietary treatment has improved the prognosis for patients with GSDIa; however, the disease itself, its management and monitoring have significant physical, psychological and psychosocial burden on individuals and parents/caregivers. Hypoglycaemia risk persists if a single dose of UCCS is delayed/missed or in cases of gastrointestinal intolerance. UCCS therapy is imprecise, does not treat the cause of disease, may trigger secondary metabolic manifestations and may not prevent long-term complications. We review the importance of and challenges associated with achieving good glycaemic/metabolic control in individuals with GSDIa and how this should be balanced with age-specific psychosocial development towards independence, management of anxiety and preservation of quality of life (QoL). The unmet need for treatment strategies that address the cause of disease, restore glucose homeostasis, reduce the risk of hypoglycaemia/secondary metabolic perturbations and improve QoL is also discussed.

Keywords: burden of disease; dietary treatment; glycogen storage disease type Ia; long-term complications; quality of life; uncooked cornstarch; unmet need.

PubMed Disclaimer

Conflict of interest statement

T.G.J.D.: Adviser for Moderna Therapeutics and Ultragenyx Pharmaceutical Inc. and principal investigator for Ultragenyx Pharmaceutical Inc, and Vitaflo International Ltd.; D.F.R.-B.: Adviser for BioMarin Pharmaceutical Inc., adviser and principal investigator for Ultragenyx Pharmaceutical Inc; A.A.: Clinical investigator for clinical trials sponsored by Applied Therapeutics, Moderna Inc. and Ultragenyx Pharmaceutical Inc.; F.d.B.: No conflicts of interest to declare; M.L.C.: No conflicts of interest to declare; S.C.G.: Honoraria for lectures and/or advisory services from MetaX, Orphan Europe, Sobi and Vitaflo; P.L.: No conflicts of interest to declare; N.L.M.: No conflicts of interest to declare; C.F.M.d.S.: No conflicts of interest to declare; R.R.-W.: Clinical Investigator for Ultragenyx Pharmaceutical Inc.; A.R.: Grant recipient (research) Nutricia Metabolics and (travel) Ultragenyx Pharmaceutical Inc and Vitaflo Italia; H.S.: Consultant and member of speaker bureau for BioMarin Pharmaceutical Inc. and consultant for Moderna Therapeutics: R.N.G.: Employee and shareholder of Ultragenyx Pharmaceutical Inc.; V.V.: Employee and shareholder of Ultragenyx Pharmaceutical Inc.; J.M.: Clinical investigator for BioMarin Pharmaceutical Inc., Regenxbio, Rezolute Inc., Sanofi Genzyme, Takeda and Ultragenyx Pharmaceutical Inc. and consultant for BioMarin Pharmaceutical Inc., Sanofi Genzyme, Takeda and Ultragenyx Pharmaceutical Inc. The authors confirm their independence from the sponsors; the content of the article has not been influenced by the sponsors.

Figures

Figure 1
Figure 1
Consequences of defective G6Pase. Defective G6Pase means glucose-6-phosphate accumulates and is shunted into other pathways leading to hyperuricaemia, hypercholesterolaemia, hypertriglyceridaemia, hyperalaninaemia and hyperlactataemia, in addition to hypoglycaemia. Acetyl-CoA—acetyl-coenzyme A; ASAT—aspartate transaminase; ALAT—alanine transaminase; CGM—continuous glucose monitoring; G6Pase—glucose-6-phophatase; QoL—quality of life.
See this image and copyright information in PMC

References

    1. Froissart R., Piraud M., Boudjemline A.M., Vianey-Saban C., Petit F., Hubert-Buron A., Eberschweiler P.T., Gajdos V., Labrune P. Glucose-6-phosphatase deficiency. Orphanet J. Rare Dis. 2011;6:27. doi: 10.1186/1750-1172-6-27. - DOI - PMC - PubMed
    1. De León D.D., Stanley C.A., Sperling M.A. Hypoglycemia in neonates and infants. In: Sperling M.A., editor. Pediatric Endocrinology. 3rd ed. W.B. Saunders; Philadelphia, PA, USA: 2008. pp. 165–197.
    1. Burr I.M., O’Neill J.A., Karzon D.T., Howard L.J., Greene H.L. Comparison of the effects of total parenteral nutrition, continuous intragastric feeding, and portacaval shunt on a patient with type I glycogen storage disease. J. Pediatr. 1974;85:792–795. doi: 10.1016/S0022-3476(74)80342-2. - DOI - PubMed
    1. Greene H.L., Slonim A.E., O’Neill J.A., Burr I.M. Continuous Nocturnal Intragastric Feeding for Management of Type 1 Glycogen-Storage Disease. N. Engl. J. Med. 1976;294:423–425. doi: 10.1056/NEJM197602192940805. - DOI - PubMed
    1. Smit G.P., Berger R., Potasnick R., Moses S.W., Fernandes J. The Dietary Treatment of Children with Type I Glycogen Storage Disease with Slow Release Carbohydrate. Pediatr. Res. 1984;18:879–881. doi: 10.1203/00006450-198409000-00015. - DOI - PubMed

MeSH terms

Supplementary concepts