Glycogen storage disease type 6

Other Names: GSD6; Glycogen storage disease 6; Hers disease; Phosphorylase deficiency glycogen-storage disease of liver

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 liver is responsible for breaking down a substance called glycogen. Glycogen is the stored form of sugar that is made by breaking down carbohydrates. When the liver cannot break down glycogen properly it causes a buildup that is damaging to the body.

Epidemiology

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.

Cause

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

Autosomal recessive inheritance, a 25% chance

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.

Signs and symptoms

Symptoms of GSD6 usually begin in infancy or childhood and may include an enlarged liver (hepatomegaly). Other symptoms of the disease include low blood sugar (hypoglycemia) or an increase in the amount of lactic acid in the blood (lactic acidosis). Hypoglycemia can also cause symptoms such as faintness, weakness, hunger, and nervousness. The symptoms of the disease are especially likely to occur when an individual does not eat for a long time.In some cases, children with glycogen storage disease type 6 have slow growth (growth retardation) or muscle weakness (hypotonia).

People with GSD6 may be at an increased risk to have liver cancer or an enlarged heart (cardiomyopathy).Many of the symptoms of GSD6 tend to improve as the child gets older. Adults with the disease frequently do not have hepatomegaly, and they are not expected to be shorter than other individuals.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Hepatomegaly(Enlarged liver)
• Increased hepatic glycogen content

30%-79% of people have these symptoms

• Delayed puberty(Delayed pubertal development)
• Elevated hepatic transaminase(High liver enzymes)
• Failure to thrive(Faltering weight)
• Hypoglycemia(Low blood sugar)
• Ketosis(High levels of ketone bodies)
• Osteopenia
• Osteoporosis

5%-29% of people have these symptoms

• Abdominal distention(Abdominal bloating)
• Exercise-induced muscle cramps(Exercise-induced muscle cramping)
• Hepatic fibrosis
• Hyperlipidemia(Elevated lipids in blood)
• Intermittent lactic acidemia
• Irritability(Irritable)
• Motor delay
• Muscular hypotonia(Low or weak muscle tone)
• Portal fibrosis
• Postexertional malaise
• Short stature(Decreased body height)
• Sleep disturbance(Difficulty sleeping)

Diagnosis

GSD6 is diagnosed when a healthcare provider observes signs and symptoms of the disease such as an enlarged liver and hypoglycemia. The diagnosis is made based on genetic testing of the PYGL gene. A liver biopsy that tests the function of liver glycogen phosphorylase may be necessary if the results of the genetic testing are not clear.

Treatment

The primary treatment for GSD6 is to avoid prolonged periods of time without eating. Because glycogen is only broken down when stored energy is needed, eating frequent meals can avoid the need to break down glycogen. Levels of blood glucose should be monitored to make sure that the diet is working properly.This will minimize the symptoms of the disease. In some cases, no other treatment is necessary. Uncooked cornstarch may be helpful for some people with GSD6. Uncooked cornstarch is a complex carbohydrate that is difficult for the body to digest; therefore it maintains normal blood sugar levels for a longer period of time than most carbohydrates in food. For children who have muscle weakness, a high-protein diet may also be recommended.

Prognosis

The signs and symptoms of GSD6 tend to improve with age. In general, it is thought that the body can adapt to low blood sugar levels and produce energy through alternate methods.Therefore, the long-term outlook for people affected by the disease is often good. However, if the symptoms of the disease are not well controlled with diet, additional symptoms such as delayed puberty and osteoporosis may develop.

Adults are typically of a normal height and do not have muscle weakness. Liver problems associated with the disease tend to resolve as people get older, and the need for treatment for liver problems is rare in adulthood.

NIH genetic and rare disease info

• NIH info on Glycogen storage disease type 6

Glycogen storage disease type 6 is a rare disease.

Glycogen storage disease type 6 Resources
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