Overview:

• Synonyms: Liver Phosphorylase Deficiency, Hers Disease
• Cause: Mutations in the PYGL gene result in deficiency of liver phosphorylase enzyme
• Effect: Abnormal glycogen degradation during fasting results in ketotic hypoglycemia and hepatomegaly

Presentation:

• Most patients are identified when an enlarged liver (hepatomegaly) is found on an exam or imaging
• May also present when AST and ALT elevation are identified on laboratory studies during an illness
• May also present as ketotic hypoglycemia
• Growth delay is common at presentation
• Mild hyperlipidemia is usually present
• Lactate and uric acid levels are normal

Diagnosis:

• Genetic testing: Identifies mutations in the PYGL gene
• Liver biopsy: Shows reduced phosphorylase activity (rarely needed)

Treatment:

• Frequent glucose and blood ketone measurements particularly with fasting are recommended
• Uncooked cornstarch: Provides steady glucose release
• Diet: A high protein diet (2-2.5 g/kg) with restricted intake of carbohydrate and sugars
• Goal: Maintain glucose >70 mg/dL and normal ketones (beta-OH-butyrate under 0.3 mmol/L)
• Cardiac involvement is rare and due to over-storage of carbohydrate
• Annual ultrasounds to screen for liver scarring
• Labs: Liver function tests, coagulation studies, ketone monitoring, protein, albumin, CK, and prealbumin

Prognosis:

• The prognosis is excellent with dietary therapy if laboratory studies are achieved
• Liver complications are rare with proper treatment
• Liver failure does not occur with proper treatment
• Muscle pain and CK elevation can occur if protein deficiency develops
• Alcohol can exacerbate hypoglycemia and must be avoided; alcohol use has been associated with seizures, liver inflammation, and liver scarring
• Growth hormone should not be used