Approach Considerations
After a GSD III diagnosis is confirmed, Dagli, Sentner, and Weinstein [4] recommend the following:
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Liver ultrasound examination to determine the size of the liver and to identify adenomas if present
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Baseline electrocardiogram and echocardiogram
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Consultation with a biochemical geneticist
Consultations
A cardiologist, neuromuscular specialist, gastroenterologist, physical therapist, occupational therapist, genetic counselor, and/or a metabolic dietitian may be consulted depending on the disease manifestations.
Medical and Surgical Care
Medical care
The mainstay of GSD III treatment is dietary modification. A dietary regimen consisting of high protein intake and cornstarch supplementation improves exercise tolerance, muscle strength and mass, electromyographic findings, and growth, and it reduces cardiomyopathy. [18, 19, 20] Simple carbohydrate intake should be limited, as excess sugar is stored as glycogen, which cannot be broken down. [4] Avoidance of prolonged fasting may prevent hypoglycemia.
Two studies have shown improvement of GSD III clinical findings using a recombinant adenoviral vector in mice. [21, 22] These findings suggest that corrective gene therapy for GSDs may be possible in humans.
An encouraging study by Bijvoet and colleagues provides evidence of successful enzyme replacement for the mouse model of Pompe disease, which may lead to therapies for other enzyme deficiencies. [23]
Surgical care
Liver transplantation may be indicated for patients with hepatic malignancy. Whether transplantation prevents further complications is not clear, although a study by Matern and colleagues demonstrated posttransplantation correction of metabolic abnormalities. [24]
Diet
Current American College of Medical Genetics and Genomics (ACMG) guidelines recommend the following in infants and children [2] :
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Small, frequent feedings (including complex carbohydrates and protein, avoiding simple sugars) and avoidance of fasting
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Introduction of cornstarch supplementation as early as the first year of life if hypoglycemia is present
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Bedtime snack, cornstarch supplementation, and/or continuous enteral feedings may be needed for the overnight fast
Current ACMG guidelines recommend the following in adolescents and adults [2] :
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High protein (25% of total calories), low complex carbohydrates (< 50% of total calories), avoidance of simple sugars, and avoidance of fasting, most importantly for those with GSD IIIa
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Bedtime snack (low-fat milk with protein powder) or a high-protein formula for overnight enteral feeding may be of benefit to those with myopathy
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Dietary restriction is transitioned to a regular well-balanced diet in GSD-IIIb
Long-Term Monitoring and Prevention
Long-term monitoring
For cardiovascular disease, current ACMG guidelines recommend the following [2] :
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Echocardiography for ventricular hypertrophy, including wall thickness, ventricular mass, and systolic and diastolic function
- For GSD IIIa, obtain baseline and repeat every 12-24 months
- For GSD IIIb, obtain baseline echocardiography for the same parameters as noted for GSD IIIa; repeat every 5 years
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Routine 12-lead ECG for arrhythmia
- For GSD IIIa, serial 12-lead ECG every 2 years
- More detailed rhythm analysis if any symptoms
For liver disease, current ACMG guidelines recommend the following [2] :
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Laboratory testing to include serum aspartate aminotransferase, alanine aminotransferase, prothrombin time, bilirubin, and albumin every 6 months to yearly, to monitor extent of hepatic damage and to delineate if there is progression of liver cirrhosis to end-stage liver failure
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Abdominal imaging should be performed at baseline and then every 12-24 months
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Abdominal computed tomography/magnetic resonance imaging with contrast should be performed in older patients every 6-12 months based on laboratory and clinical findings
A physical therapy evaluation is recommended every 6 months or more frequently based on physical status, function, or need. [2]
Prevention
Genetic counseling is recommended to all parents with a child with GSD III and to all adults with GSD III. [2]
Molecular testing is the preferred method for prenatal diagnosis when both mutations are known. [2]
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Metabolic pathways of carbohydrates.
