Medical Care

Diagnostic evaluation of glycogen-storage disease type I (GSD I) is most safely performed in a hospital, especially in infants, because of the potential for severe hypoglycemia. Many untreated children are admitted by a hematologist or gastroenterologist for the diagnosis of massive hepatomegaly.

Young infants require continuous nasogastric (NG) tube feedings to sustain blood sugar levels. Older children can usually be switched to raw cornstarch feedings, which sustain blood glucose values for 4-6 hours. Trials using chemically-altered cornstarch that resulted in longer-term blood sugar support have been reported; these products are not yet widely available.^[11] Large quantities of raw cornstarch may be necessary, because overall use of this material is impaired in patients compared with healthy control subjects.

Pay scrupulous attention to the dental and oral health of patients with glycogen-storage disease type Ib to reduce incidence of infection.

Any intercurrent infection that causes decreased intake requires intravenous (IV) glucose support until resolution.

Currently, efforts are underway in animal models to develop gene therapy in patients with both forms of glycogen-storage disease type I.^[12]

Surgical Care

Surgery is usually unnecessary after initial diagnosis.

Promptly attend to any skin infection in patients with glycogen-storage disease type Ib because deep-tissue extension requiring surgical debridement and plastic reconstruction may develop.

In older children with glycogen-storage disease type Ib, cautiously evaluate abdominal pain for pseudocolitis.

Perform ultrasonography annually to evaluate for hepatic adenomas, which may require surgical removal.

Hepatic transplantation has been attempted in a few cases with modified success.

Consultations

Consider the following consultations:

Biochemical genetics specialist
Nephrologist

Diet

Diet, the mainstay of therapy for both types of glycogen-storage disease type I, requires close monitoring and adjustment by a highly specialized nutritionist.

The fundamental principle of diet management for these patients is maintenance of a steady-state balance between circulating glucose and existing glycogen stores. Consequently, a chief aim is to avoid excessive carbohydrates and calories while supplying adequate calories and protein for growth.

Because of the triglyceridemia characteristic in this disorder, counsel the patient to avoid high lipid intake.^[13]

Most biochemical parameters can be substantially normalized and liver size can be reduced by approaching glucose homeostasis by means of overnight feeding.

Overnight NG feedings should be administered only by a pump equipped with an alarm in case of flow interruption.

When pancreatic amylase reaches sufficient activity in children older than 2-3 years, overnight feeding is usually replaced by raw cornstarch at bedtime and early morning hours.

Activity

Instruct the patient to avoid all contact sports because of the propensity for infection and bleeding, as well as the potential for liver damage.

Encourage the patient to engage in all other physical activities up to individual limits. Personal limitations should be the basis for participation in school activities.

Medication

Cori GT, Cori CF. Glucose-6-phosphatase of the liver in glycogen storage disease. J Biol Chem. 1952 Dec. 199(2):661-7. [QxMD MEDLINE Link].
Narisawa K, Igarashi Y, Otomo H, Tada K. A new variant of glycogen storage disease type I probably due to a defect in the glucose-6-phosphate transport system. Biochem Biophys Res Commun. 1978 Aug 29. 83(4):1360-4. [QxMD MEDLINE Link].
Kishnani PS, Austin SL, Abdenur JE, Arn P, Bali DS, Boney A, et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. Genet Med. 2014 Nov. 16 (11):e1. [QxMD MEDLINE Link].
Nguyen AD, Pan CJ, Weinstein DA, Chou JY. Increased scavenger receptor class B type I-mediated cellular cholesterol efflux and antioxidant capacity in the sera of glycogen storage disease type Ia patients. Mol Genet Metab. 2006 Nov. 89(3):233-8. [QxMD MEDLINE Link].
Melis D, Cozzolino M, Minopoli G, et al. Progression of renal damage in glycogen storage disease type I is associated to hyperlipidemia: a multicenter prospective Italian study. J Pediatr. April 2015. 166:1079-1082. [QxMD MEDLINE Link].
Bernier AV, Correia CE, Haller MJ, et al. Vascular dysfunction in glycogen storage disease type I. J Pediatr. 2009 Apr. 154(4):588-91. [QxMD MEDLINE Link].
Cabrera-Abreu J, Crabtree NJ, Elias E, et al. Bone mineral density and markers of bone turnover in patients with glycogen storage disease types I, III and IX. J Inherit Metab Dis. 2004. 27(1):1-9. [QxMD MEDLINE Link].
Minarich LA, Kirpich A, Fiske LM, Weinstein DA. Bone mineral density in glycogen storage disease type Ia and Ib. Genet Med. 2012 Apr 5. [QxMD MEDLINE Link].
Sim SW, Park TS, Kim SJ, Park BC, Weinstein DA, Lee YM, et al. Aberrant proliferation and differentiation of glycogen storage disease type Ib mesenchymal stem cells. FEBS Lett. 2018 Jan. 592 (2):162-171. [QxMD MEDLINE Link].
Calderaro J, Labrune P, Morcrette G, et al. Molecular characterization of hepatocellular adenomas developed in patients with glycogen storage disease type I. J Hepatol. 2013 Feb. 58(2):350-7. [QxMD MEDLINE Link].
Correia CE, Bhattacharya K, Lee PJ, et al. Use of modified cornstarch therapy to extend fasting in glycogen storage disease types Ia and Ib. Am J Clin Nutr. 2008 Nov. 88(5):1272-6. [QxMD MEDLINE Link].
Koeberl DD. In search of proof-of-concept: gene therapy for glycogen storage disease type Ia. J Inherit Metab Dis. 2012 Feb 7. [QxMD MEDLINE Link].
Das AM, Lücke T, Meyer U, Hartmann H, Illsinger S. Glycogen storage disease type 1: impact of medium-chain triglycerides on metabolic control and growth. Ann Nutr Metab. 2010. 56(3):225-32. [QxMD MEDLINE Link].
Melis D, Pivonello R, Cozzolino M, et al. Impaired bone metabolism in glycogen storage disease type I is associated with poor metabolic control in type Ia and with granulocyte-colony stimulating factor therapy in type Ib. Horm Res Paediatr. January 2014. 81:55-62. [QxMD MEDLINE Link].

Media Gallery

Microsome is shown in relation to the substrate, glucose-6-phosphate, which has been released from cytosolic glycogen. This substrate is transferred across the microsomal membrane by the protein translocase, where by glucose-6-phosphatase acts on it to release free glucose and inorganic phosphate. Patients with glycogen-storage disease type Ia are genetically deficient in glucose-6-phosphate activity, while those affected with glycogen-storage disease type Ib lack translocase.

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