The enzymes responsible for converting stored glycogen into glucose are not working:

• GSD Ia: Glucose-6-phosphatase deficiency
• GSD Ib: Glucose-6-phosphate transporter deficiency

This leads to:

• Severe hypoglycemia (low blood sugar)
• Lactic acidosis
• High triglycerides
• High uric acid
• Enlarged liver (hepatomegaly)

• Low blood sugar with sweating, shakiness, seizures
• Enlarged liver, swollen abdomen
• Poor growth
• Lactic acidosis (rapid breathing during illness)
• Recurrent nosebleeds
• GSD Ib specifically: neutropenia → frequent infections, mouth ulcers

• Low blood glucose during fasting
• High lactate, triglycerides, cholesterol, and uric acid
• Genetic testing for G6PC or SLC37A4 mutations
• Liver biopsy is rarely needed now

Diet is the main treatment:

• Strict avoidance of fasting
• Frequent daytime meals
• Uncooked cornstarch therapy every 3–4 hours to maintain blood sugar
• High complex-carbohydrate diet
• Avoid sucrose, fructose, and galactose

• Allopurinol (for high uric acid)
• Lipid-lowering medications
• G-CSF for neutropenia (GSD Ib)

• Monitor liver for adenomas
• Screen kidneys for dysfunction
• Maintain normal growth and puberty
• Liver transplant if recurrent seizures are not controlled by diet or if cyclical neutropenia does not respond to medications

Glycogen Storage Disease Type III (GSD III) is caused by a deficiency of the debranching enzyme, resulting in incomplete breakdown of glycogen. This condition affects the liver, muscles, and sometimes the heart. It is generally less severe than Type I.

Two major forms ecist:

• GSD IIIa: Liver + muscle + heart involvement
• GSD IIIb: Liver-only involvement

The debranching enzyme deficiency Causes:

• Accumulation of abnormal glycogen in the liver and muscles
• Poor release of glucose during fasting
• Episodes of low blood sugar
• Progressive muscle weakness (especially in GSD IIIa)

Childhood:

• Enlarged liver
• Low blood sugar during fasting
• Poor growth
• High triglycerides
• Elevated liver enzymes

Later Childhood / Teens:

• Muscle weakness (IIIa)
• Exercise intolerance
• Heart muscle thickening (cardiomyopathy in some)

• blood sugar when fasting
• High liver enzymes (ALT/AST)
• High CK in IIIa
• Abnormal glycogen structure on testing
• Genetic testing for AGL gene

Diet:

• Frequent meals
• Uncooked cornstarch therapy
• High-protein diet to support muscle health
• Avoid long fasting periods
• During illness: emergency glucose plan

Monitoring:

• Liver size and function
• Muscle strength and CK levels
• Heart function (echocardiogram)
• Growth and school performance

Children with GSD III often improve in puberty as liver Shrinks and blood sugars stabilize. Adults may develop muscle weakness or heart issues, so lifelong monitoring is important. Most individuals lead normal, productive lives with proper care.

Glycogen Storage Disease Type IV (GSD IV) is a rare and more serious glycogen storage disease caused by deficiency of the branching enzyme. This leads to accumulation of abnormal glycogen (“amylopectin-like”) in tissues—especially the liver, heart, and muscles This condition can present with jaundice and liver chirrhosis..

GSD IV has several subtypes ranging from severe infantile disease to milder childhood forms.

Without the branching enzyme:

• Glycogen becomes abnormal and toxic
• Liver cells are damaged → cirrhosis
• Muscle and heart tissue may also be affected

Symptoms vary by subtype but may include:

Severe infantile liver form:

• Enlarged liver
• Poor growth
• Vomiting and feeding problems
• Progressive liver failure
• Jaundice
• Abdominal distension

Other forms:

• Muscle weakness
• Dilated or hypertrophic cardiomyopathy
• Exercise intolerance
• Early fatigue

• High liver enzymes
• Enlarged liver on examination
• Abnormal glycogen on liver biopsy (if needed)
• Genetic testing confirming GBE1 mutations

Diagnosis often occurs early due to liver symptoms.

Liver disease care:

• Nutritional support
• Avoiding fasting
• Monitoring for cirrhosis

Liver Transplantation:

This is the only effective treatment for the progressive liver form. It:

• Stops liver failure
• Improves growth
• Does not fully correct muscle or heart involvement if present

Ongoing Monitoring:

• Heart function
• Muscle strength
• Growth and development
• Screening for complications

• Severe liver form: Without transplant, progression to liver failure is common.
• Non-liver forms: Muscle and heart involvement determine long-term outlook.
• With early liver transplant: Many children achieve good quality of life.