Overview

• Synonyms: Debranching enzyme deficiency, Cori Disease, Forbes Disease
• Incidence: ~1 in 1,000,000 live births in the United States
• Cause: Deficiency of debranching enzyme due to mutation in the AGL gene
• Effect: Abnormal glycogen breakdown results in limited glucose release and abnormal glycogen which accumulates in affected tissues

Subtypes:

Presenting Symptoms:

• Severe hepatomegaly (liver enlargement) with a firm liver
• Marked AST / ALT elevation found on laboratory studies during an illness (> 1,000 U/L)
• Ketotic hypoglycemia
• Muscle weakness and delayed attainment of motor milestones

Diagnosis:

• Diagnosis should be considered in anyone with hepatomegaly, AST/ALT elevation, and ketotic hypoglycemia
• CK often is not elevated in infants and does not rule out GSD IIIa
• Genetic testing: Identifies mutations in the AGL gene
• Liver and Muscle Biopsies are rarely required

Treatment:

• A team with expertise in GSD is highly recommended along with a cardiologist
• Frequent glucose monitoring and ketone monitoring are recommended
• Continuous glucose monitoring may be helpful when hypoglycemia is occurring
• Uncooked cornstarch for slow glucose release beginning at 6-12 months
• Diet: A high protein diet (3-4 g/kg) with restricted intake of carbohydrate and sugars
• Avoidance of maximal exertion exercise (i.e. sprinting) is critical
• Annual echocardiograms to screen for hypertrophic cardiomyopathy
• Labs: Liver function tests, total protein, prealbumin, CK, triglycerides

Complications:

With good metabolic control, most if not all complications are preventable.  Potential complications include:

• Liver: Cirrhosis, hepatic adenomas, and liver cancer
• Muscle: Muscle pain and progressive muscle weakness which can become debilitating
• Heart: Hypertrophic cardiomyopathy (from over-storage of glycogen)
• Others: Osteopenia, type 2 diabetes,

Prognosis:

• The prognosis for individuals with GSD III is excellent with good metabolic control (near normal CK and LFTs)
• Hypoglycemia is common in childhood and adolescence
• Progressive muscle weakness can develop during adolescence especially in the setting of low protein intake
• The heart disease is usually reversible if carbohydrates are restricted
• Alcohol and growth hormone should be avoided