Glycogen storage disease type VI

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Glycogen storage disease type VI (also known as GSDVI or Hers disease) is an inherited disorder caused by an inability to break down a complex sugar called glycogen in liver cells. A lack of glycogen breakdown interferes with the normal function of the liver.

The signs and symptoms of GSDVI typically begin in infancy to early childhood. The first sign is usually an enlarged liver (hepatomegaly). During prolonged periods without food (fasting), affected individuals may have low blood sugar (hypoglycemia) or elevated levels of ketones in the blood (ketosis). Ketones are molecules produced during the breakdown of fats, which occurs when stored sugars are unavailable. Children with GSDVI tend to grow slower than their peers, but they often achieve normal height as adults. Some affected children also have mild delays in the development of motor skills, such as sitting, standing, or walking.

The signs and symptoms of GSDVI tend to improve with age; most adults with this condition do not have any related health problems.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the PYGL gene cause GSDVI. The PYGL gene provides instructions for making an enzyme called liver glycogen phosphorylase. This enzyme is found only in liver cells, where it breaks down glycogen into a type of sugar called glucose-1-phosphate. Additional steps convert glucose-1-phosphate into glucose, a simple sugar that is the main energy source for most cells in the body.

PYGL gene mutations prevent liver glycogen phosphorylase from breaking down glycogen effectively. Because liver cells cannot break down glycogen into glucose, individuals with GSDVI can have hypoglycemia and may use fats for energy, resulting in ketosis. Glycogen accumulates within liver cells, causing these cells to become enlarged and dysfunctional.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The exact prevalence of GSDVI is unknown. At least 11 cases have been reported in the medical literature, although this condition is likely to be underdiagnosed because it can be difficult to detect in children with mild symptoms or adults with no symptoms. GSDVI is more common in the Old Older Mennonite population, with an estimated incidence of 1 in 1,000 individuals.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Hepatomegaly · Very frequent (99-80%)

Abnormally increased size of the liver.

Increased hepatic glycogen content · Very frequent (99-80%)

An increase in the amount of glycogen stored in hepatocytes compared to normal.

Delayed puberty · Frequent (79-30%)

Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.

Elevated circulating hepatic transaminase concentration · Frequent (79-30%)

Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.

Failure to thrive · Frequent (79-30%)

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Growth delay · Frequent (79-30%)

A deficiency or slowing down of growth pre- and postnatally.

Hypoglycemia · Frequent (79-30%)

A decreased concentration of glucose in the blood.

Ketosis · Frequent (79-30%)

Presence of elevated levels of ketone bodies in the body.

Osteopenia · Frequent (79-30%)

Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.

Osteoporosis · Frequent (79-30%)

Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).

Abdominal distention · Occasional (29-5%)

Distention of the abdomen.

Exercise-induced muscle cramps · Occasional (29-5%)

Sudden and involuntary contractions of one or more muscles brought on by physical exertion.

Hepatic fibrosis · Occasional (29-5%)

The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.

Hyperlipidemia · Occasional (29-5%)

The concentration of lipid in the blood circulation is above the upper limit of normal.

Other findings in the same source

From: Orphanet

Additional reported features include Hypotonia (Occasional (29-5%)); Intermittent lactic acidemia (Occasional (29-5%)); Irritability (Occasional (29-5%)); Motor delay (Occasional (29-5%)); Portal fibrosis (Occasional (29-5%)); Postexertional malaise (Occasional (29-5%)); Short stature (Occasional (29-5%)); Sleep abnormality (Occasional (29-5%)); Abnormality of the kidney (Very rare (<4-1%)); Cirrhosis (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Glycogen storage disease type VI is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Glycogen storage disease type VI. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.