Von Gierke disease (glycogen storage disease type 1): symptoms, treatment and outlook

Glycogen is the form in which the body stores sugar for later use. Contact explains that glycogen is stored in the liver and muscle as an energy store, with the liver’s supply used between meals, and that releasing energy from glycogen takes a series of chemical reactions, each needing an enzyme. In glycogen storage diseases (GSDs), an enzyme deficiency causes glycogen to accumulate.

In GSD type 1, also named von Gierke disease, the missing enzyme is glucose-6-phosphatase. AGSD-UK says children with GSD1 are unable to release glucose from liver glycogen, so that if untreated they have prolonged periods when blood sugar is too low, and their livers become enlarged because glycogen that cannot be broken down accumulates.

There are two subtypes: 1a (glucose-6-phosphatase deficiency) and 1b (glucose-6-phosphatase translocase deficiency). Both are inherited in an autosomal recessive way, which means a child inherits a changed copy of the relevant gene from each parent.

AGSD-UK says that children become unwell in early childhood with sweating, irritability, poor growth and muscle weakness, together with an enlarged liver. They can also develop frequent mouth ulcers and are at increased risk of infection.

Contact says that liver GSDs cause liver enlargement with a tendency for low blood sugar, and that untreated children tend to be short, with enlarged abdomens and thin limbs; it adds that these problems improve dramatically with treatment. It also notes that all types of GSD are at risk of osteopaenia, meaning reduced bone strength, which increases fracture risk in later life.

• Sweating, irritability and poor growth during childhood.

• An enlarged liver and a tendency to low blood sugar.

• Muscle weakness.

• Mouth ulcers and a higher risk of infection, particularly in type 1b.

• In later life, risk of reduced bone strength.

Contact says it is possible to test the level of certain enzymes in a specialist laboratory, but this may require a sample of affected tissue such as liver. It adds that it is often more straightforward to look at the genes that provide the code to make the enzymes, to see whether any are changed.

Prenatal diagnosis is usually available if required, by looking for the gene change in a chorionic villus biopsy, according to Contact. Families who already have a child with GSD1 can ask a genetics service about this and about carrier testing for relatives.

The sources used for this page do not set out the full diagnostic pathway, so the details of who arranges which test, and when, come from the child’s treating team.

Contact explains that treatment for GSD varies with the type, and that children with liver GSDs need frequent daytime feeding and often overnight continuous tube feeding to prevent low blood sugar and to improve growth. In older children and adults this may be replaced with regular starches that are slow releasers of energy.

AGSD-UK describes the same approach for GSD1: initially glucose via a nasogastric tube, with glucose replaced by cornstarch taken orally as children get older.

The aim is to avoid long gaps without a supply of glucose. Because the details of feed timing and quantities depend on age, subtype and other factors, they are managed by a specialist metabolic dietitian and doctor rather than self-directed.

Contact says a few people with liver GSDs may develop liver scarring and very occasionally liver tumours, and that in GSD I there can be longer-term problems with kidney disease. People with type 1b have an increased risk of infections due to a decrease in a particular type of white blood cell. AGSD-UK likewise lists mouth ulcers and an increased risk of infection as secondary symptoms.

Because these problems can develop over time, regular review with a specialist metabolic team is the usual pattern. Specific monitoring schedules are not given in the sources used here, so they are not listed.

AGSD-UK says that most children do well and that symptoms improve as they reach adulthood. Contact says the prognosis for patients with a liver GSD is usually good and that the tendency to low blood sugar always improves with age, though people who are more severely affected will still need regular treatment even as adults.

AGSD-UK also describes practical support: a GSD1 coordinator, a specialist care adviser for non-clinical help with education, work rights, social care, transport, housing and community grants, a benefits adviser, a map to help find peer support, and an illustrated booklet for children with GSD1a. It also notes a first gene therapy trial among its research news.

Peer groups on social media can be valuable, though AGSD-UK reminds readers that such groups are not run by medical professionals and that someone’s opinion should not be treated as scientific fact.

GSD1 is a rare metabolic condition managed within NHS paediatric and adult metabolic services, usually through a specialist centre with a dietitian experienced in glycogen storage diseases. The GP and local paediatric team provide day-to-day care and co-ordinate with the centre.

Private care is uncommon for a lifelong condition that depends on specialist dietetic support, but some families use it for second opinions. Sharing the plan between providers helps avoid conflicting feeding advice.