What are the symptoms of Andersen disease?

September 21, 2025 •

4 min read

Andersen disease, also known as glycogen storage disease type IV (GSD IV), is a rare genetic disorder characterized by the body's inability to properly form glycogen. The answer to what are the symptoms of Andersen disease depends on the specific subtype, as the disease can affect multiple organ systems, most notably the liver, muscles, and nerves.

Quick Summary

Symptoms of Andersen disease vary by subtype and age of onset, including failure to thrive, enlarged liver, and progressive cirrhosis in infants, or muscle weakness and neurological problems in later-onset forms.

Key Points

Hepatic Symptoms: In infants, common signs include failure to thrive, an enlarged liver and spleen, and progressive cirrhosis, which can lead to early liver failure.
Neuromuscular Symptoms: Later-onset forms can cause muscle weakness (myopathy), low muscle tone (hypotonia), and dilated cardiomyopathy.
Adult-Onset Signs: The adult form (APBD) primarily affects the nervous system, leading to gait problems, bladder dysfunction, and cognitive difficulties.
Severe Infant Forms: The perinatal and congenital subtypes are often fatal, presenting with severe hypotonia, respiratory distress, and heart failure shortly after birth.
Variable Presentation: Andersen disease is highly heterogeneous; its symptoms depend on the specific subtype, age of onset, and affected organ systems.
Diagnostic Methods: Diagnosis is confirmed via enzyme assays or genetic testing for mutations in the GBE1 gene.

Understanding Andersen Disease and Its Subtypes

Andersen disease is a rare, inherited metabolic disorder caused by mutations in the GBE1 gene, which codes for the glycogen-branching enzyme. This enzyme is crucial for creating the complex structure of glycogen, the body's storage form of glucose. Without a functional branching enzyme, the body produces an abnormal, amylopectin-like glycogen that is less soluble and builds up in various tissues, causing cellular injury and dysfunction. The clinical presentation is highly variable and has been classified into several distinct subtypes based on the age of onset and primary symptoms.

Symptoms of the Classic (Progressive) Hepatic Subtype

This is the most common form of Andersen disease, with symptoms typically appearing within the first 18 months of life. These symptoms are primarily related to liver damage and systemic failure.

Failure to Thrive: Infants fail to gain weight and grow at the expected rate.
Hepatomegaly and Splenomegaly: The liver and spleen become abnormally enlarged due to the accumulation of abnormal glycogen.
Progressive Cirrhosis: The liver develops extensive scarring, which progresses rapidly and can lead to irreversible liver failure.
Portal Hypertension: As cirrhosis advances, blood pressure in the vein leading to the liver increases, causing complications like ascites (fluid accumulation in the abdomen) and esophageal varices.
Hypotonia: Low muscle tone, or "floppy baby" syndrome, can develop by age 1 or 2.
Cardiomyopathy: In some cases, the heart muscle can be affected.

Symptoms of Neuromuscular Subtypes

Andersen disease can also manifest with symptoms primarily affecting the muscles and nervous system. These forms can appear at different stages of life and vary in severity.

Fatal Perinatal Neuromuscular Type

This is the most severe subtype, with symptoms developing before birth.

Fetal Akinesia: Decreased fetal movement observed in utero.
Polyhydramnios: Excessive amniotic fluid.
Arthrogryposis: Multiple joint stiffness and contractures present at birth.
Severe Hypotonia: Extremely low muscle tone in newborns.
Cardiomyopathy: A weakened, enlarged heart.

Congenital Muscular Type

This form appears in early infancy and is characterized by severe muscle and heart issues.

Severe Hypotonia: Profoundly low muscle tone affecting movement and breathing.
Dilated Cardiomyopathy: Enlarged and weakened heart muscle, leading to poor circulation.
Respiratory Distress: Weakened breathing muscles often contribute to early mortality.

Childhood Neuromuscular Type

With onset in late childhood, this rare form presents differently.

Myopathy: Progressive muscle weakness.
Cardiomyopathy: A gradual weakening of the heart muscle.
Variable Progression: The course can range from mild symptoms to a severe, progressive disease.

Adult Polyglucosan Body Disease (APBD)

This is a later-onset, adult form of the disorder, and is often associated with individuals of Ashkenazi Jewish descent.

Gait Difficulties: Problems with walking, often including spasticity and weakness.
Neurological Dysfunction: Mixed upper and lower motor neuron involvement.
Sensory Loss: Numbness or reduced sensation, particularly in the lower extremities.
Neurogenic Bladder: Issues with bladder control and function.
Cognitive Decline: Mild cognitive difficulties, such as problems with executive function and abstract reasoning.

Comparison of Andersen Disease Subtypes

To better illustrate the differences, the following table summarizes the primary symptoms and typical onset for the major subtypes.


Feature	Classic (Progressive) Hepatic	Fatal Perinatal Neuromuscular	Adult Polyglucosan Body Disease
Onset	First months of life	Before birth	Adulthood
Key Symptoms	Failure to thrive, hepatosplenomegaly, progressive cirrhosis, hypotonia	Fetal akinesia, severe hypotonia, cardiomyopathy, arthrogryposis	Gait difficulties, neuropathy, neurogenic bladder, cognitive issues
Primary Organ Affected	Liver	Muscles, Heart	Nerves, Spinal Cord, Brain
Prognosis	Poor without transplant; early childhood death typical	Fatal in the neonatal period	Progressive disability; longer life expectancy

Diagnosis and Management

Diagnosing Andersen disease involves clinical evaluation, observation of symptoms, and laboratory tests. Definitive diagnosis is made by measuring GBE enzyme activity in a tissue sample, or through genetic testing for mutations in the GBE1 gene. Management is symptomatic and supportive, focusing on the specific health challenges presented by the subtype. In severe cases of classic hepatic disease, liver transplantation may be considered. However, as the abnormal glycogen can accumulate in other organs post-transplant, this is not a complete cure.

For more in-depth information, you can read about Andersen disease on the National Organization for Rare Disorders (NORD) website at rarediseases.org/rare-diseases/andersen-disease-gsd-iv/.

Conclusion

Andersen disease is a complex genetic condition with a wide spectrum of symptoms, ranging from severe and life-threatening in infancy to chronic and debilitating in adulthood. Recognizing the specific symptoms associated with each subtype is critical for accurate diagnosis and determining the best course of supportive management. The accumulation of abnormal glycogen affects different tissues depending on the form, leading to the diverse clinical outcomes observed in patients. Early diagnosis is key to providing appropriate medical and supportive care tailored to the patient's specific presentation.

Frequently Asked Questions

Andersen disease, or glycogen storage disease type IV (GSD IV), is a rare genetic disorder caused by a deficiency in the glycogen-branching enzyme, leading to the accumulation of abnormal glycogen in tissues.

Yes, there are several distinct subtypes, including fatal perinatal, congenital muscular, classic hepatic, non-progressive hepatic, and adult polyglucosan body disease (APBD).

In the common classic hepatic subtype, initial signs typically include failure to thrive (poor growth and weight gain) and an enlarged liver and spleen (hepatosplenomegaly) within the first months of life.

Yes, certain neuromuscular subtypes can cause severe hypotonia (low muscle tone), myopathy (muscle weakness), and exercise intolerance, depending on the age of onset.

The prognosis varies greatly by subtype. The perinatal and congenital muscular forms are often fatal in infancy, while the classic hepatic form can be fatal in early childhood without a liver transplant. Later-onset forms typically have a longer life expectancy with progressive disability.

Yes, the adult-onset form is known as Adult Polyglucosan Body Disease (APBD). It affects the nervous system, causing gait difficulties, sensory loss, and bladder control issues.

Diagnosis is often confirmed through a tissue biopsy to detect abnormal glycogen and decreased glycogen branching enzyme activity. Genetic testing for mutations in the GBE1 gene is also used.