Type Ia Glycogen Storage Disease Treatment & Management

Updated: Jul 07, 2021
  • Author: Kathleen R Ruddiman, DO; Chief Editor: George T Griffing, MD  more...
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Treatment

Medical Care

Current treatment modalities

In general, no specific treatment exists to cure glycogen storage diseases (GSDs).

In most cases, the mainstay of management involves measures to reduce hypoglycemia, including frequent meals and consumption of uncooked cornstarch. Some patients require continuous nocturnal gastric drip feeding via nasogastric tube to prevent nocturnal hypoglycemia. [9]

Therapies to reduce comorbidities remain common. Ai et al utilized low molecular weight heparin, insulin, and fenofibrate to reduce hypertriglyceridemia, as well as orlistat and ezetimibe to reduce hyperlipemia, to manage a case of acute pancreatitis in a 23-year-old patient with GSD Ia.  Fenofibrate, orlistat, and ezetimibe were continued after hospital discharge for long-term preventive lipid-lowering therapy. [4]

Xanthine oxidase inhibitors are commonly used to treat hyperuricemia associated with GSD Ia.

Calcium and vitamin D supplementation has been used to slow development of osteoporosis associated with GSD Ia.

In patients who suffer significant progression of kidney disease, hemodialysis may be required.

Antihypertensive medications are commonly required. As demonstrated in a retrospective analysis, hypertension notably presents much earlier, at a median age of 17 years. [9]

Future prospects for treatment options 

Zingone et al demonstrated the abolition of the murine clinical manifestations of von Gierke disease with a recombinant adenoviral vector. [17]  These findings suggested that corrective gene therapy of GSDs may be possible for humans.

An encouraging study by Bijvoet et al provides evidence of successful enzyme replacement for the mouse model of Pompe disease, which may lead to therapies for other enzyme deficiencies. [18]

Other studies have shown the prevention of hepatic adenoma and carcinoma in mice when G6Pase hepatic activity was restored to >3%, and there is a current hypothesis that damage to the liver in GSD Ia may be precipitated by abnormalities in hepatic autophagy, a process for recycling and eliminating compromised organelles to maintain efficient cellular metabolism. G6Pase deficiency in GSD Ia has been associated with dysregulation of hepatic autophagy, a pathway that may lead to the development of hepatocellular carcinoma. A publication by Zhang et al postulates that  modulation of hepatic autophagy may be a viable target for future therapies. This group tested a recombinant adeno-associated virus (rAAV) vector that introduces an amino acid substitution into the existing G6PC gene sequence, which allowed G6PC -/- mice to survive long term. [19] This may translate into viable genetic therapy based on the rAAV vector for human patients in the future. 

A CRISPR/Cas-9 based genome editing therapy was tested in mice to target a G6PC-p.R83C variant that is prevalent in humans. The study showed that treated mice had increased G6Pase activity to >3% and tolerated longer periods of fasting, which may lead to the development of genetic therapy for GSD Ia. [20]

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Surgical Care and Consultations

Surgical care

Partial liver resection or liver transplantation may be required in patients with hepatic adenomas. Whether transplantation prevents further complications remains unclear, although a study by Matern et al demonstrated the correction of metabolic abnormalities after transplantation. [21]

Patients whose kidney function deteriorates may also require kidney transplant.

Consultations

Owing to the progressive kidney dysfunction, referral to a nephrologist may be appropriate.

Consultation with a hepatologist may be necessary for management of liver dysfunction.

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Diet

Prevention of hypoglycemia in affected infants can be challenging. Nasogastric drip-feeding has allowed continuous feeding during the night. Uncooked cornstarch is another commonly used dietary intervention. Lactose- and fructose-restricted diets may also help in limiting pathways that lead to lactic acid production. [9]

Early diet therapy may help prevent hepatic disease and developmental delay.

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