What is von Gierke disease?

Risk Factors

Von Gierke disease is an autosomal recessive trait that requires that both
parents pass on the mutations. In September 2013, Deeksha Bali reported eighty
percent of cases are type Ia, and 20 percent are type Ib. The incidence is about
one case per 100,000 births. Type Ia is more common in Ashkenazi Jewish populations, where the incidence is 1 case per 20,000 births.

Etiology and Genetics

Normally, the body stores excess sugar as glycogen in the liver and kidneys. As the glucose is needed for energy and to
support body functions, it is freed from the glycogen by a process that requires
the enzyme G6P. A
similar process converts proteins and fats to glucose. Without G6P, blood glucose
levels are unstable, and the body develops large stores of glycogen. The drop in
blood glucose levels several hours after meals or at night causes severe
hypoglycemia, which can be fatal. Chronic hypoglycemia
causes other problems of metabolism. Levels of lactic acid, triglycerides, and
uric acid are elevated.

Von Gierke type Ia is caused by mutations on chromosome 17 at 17q21. As
reported by Roseline Froissart et al, more than eighty-five mutations had been
identified as of May 2011. Mutations tend to vary according to country of origin.
The more common mutations are R83C, Q347X,
459insTA, and R83H. These mutations stop
production of G6P. According to Deeksha Bali et al, there have been no strong
genotype-phenotype correlations identified for Von Gierke disease.

Von Gierke type Ib is caused by the absence of translocator1 gene
(G6PT1) located on chromosome 11 at 11q23. Some of the
mutations are due to splicing bases from one exon to another. Froissart reports
more than eighty mutations have been identified. The more common mutations are
1211delCT, G339C, and
W188Rv.

Symptoms

Symptoms of von Gierke disease develop right after birth and can be fatal if not treated. The infant can demonstrate symptoms of irritability, tremors, cyanosis, seizures, apnea, and coma. Usually, the disease is diagnosed at this time. If not, the child exhibits lethargy, difficult arousal from overnight sleep, overwhelming hunger, poor growth, increase in abdominal girth, easy bruising, and puffy cheeks as a result of fat deposits.

Older patients have poor tolerance of fasting, severe hepatomegaly, growth retardation, osteoporosis, gout, and enlarged kidneys. With type Ib, there are frequent infections.

Screening and Diagnosis

Due to its rarity, von Gierke disease is not screened for unless there is a family history. The diagnosis includes the presenting symptoms. Blood tests of glucose, lactic acid, triglycerides, and uric acid are performed four hours after eating. Typically, the blood glucose is quite low, while lactic acid, triglycerides, and uric acid are elevated. For type Ib, a complete blood count with white cell differential is performed to evaluate for decreased neutrophils. Ultrasounds of the liver and kidneys demonstrate organ enlargement.

The liver is biopsied and examined for G6P activity and deposits of glycogen.
Growth and development is behind schedule. Genetic
testing is performed for the chromosomal changes that occur
with von Gierke disease.

Treatment and Therapy

Von Gierke disease is treated by a diet that is high in starches and glucose.
According to guidelines from the European Study on Glycogen Storage
Disease, as reported by Rake et al, this diet should be 60 to 70
percent carbohydrate, 10 to 15 percent protein, and the remainder from fat.
Galactose, fructose, sucrose, and lactose should be avoided, since these sugars
require G6P to be converted to glucose. Carbohydrates, such as glucose or corn
starch, are provided during the night. This is done using a gastric tube with
continuous infusion of glucose or starch, or by night feedings with uncooked corn
starch.

Elevated uric acid levels are treated with the drug allopurinal, which
interferes with its production. During childhood, episodes of metabolic acidosis
can occur during minor illnesses or vomiting. They are treated with intravenous
fluids in order to restore glucose levels. If all else fails, a liver transplant
can be performed to treat von Gierke disease.

Prevention and Outcomes

There is no way to prevent von Gierke disease unless there is a family history
of the condition. In this case, genetic testing is performed.

There is no cure for the disease. Patients should be taught to observe for
hypoglycemia and how to treat it. Long-term complications of von Gierke disease
include seizures, kidney failure, hepatic tumors, kidney stones, and brain damage.
Type Ib can also lead to inflammatory bowel disease, frequent lung and skin
infections, secondary diabetes mellitus, and acute myelogenous leukemia.

Bibliography

Bali, Deeksha S., Yuan-Tsong Chen and
Jennifer L Goldstein. "Glycogen Storage Disease Type I."
GeneReviews. Ed. Roberta A. Pagon et al. Seattle: U of
Washington, Seattle, 1993–2014. NCBI Bookshelf. Natl.
Center for Biotechnology Information, 19 Sept. 2013. Web. 11 Aug.
2014.

Froissart, Roseline, et al.
"Glucose-6-Phosphatase Deficiency." Orphanet Journal of Rare
Diseases 6.27 (2011): n. pag. Web 18 Aug. 2014.

Haldeman-Englert, Chad. "Von Gierke Disease."
MedlinePlus. US Natl. Lib. of Medicine, 7 May 2013. Web.
11 Aug. 2014.

Nussbaum, Robert,
Roderick R. McInnes, and Huntington F. Willard. Thompson and
Thompson Genetics in Medicine. 7th ed. Philadelphia: Saunders,
2007. Print.

Pritchard, Dorian J.,
and Bruce R. Korf. Medical Genetics at a Glance. 3rd ed.
Hoboken: Wiley-Blackwell, 2013. Print.

Rake, JP, et al. "Guidelines for Management
of Glycogen Storage Disease Type I - European Study on Glycogen Storage
Disease Type I (ESGSD I)." European Journal of Pediatrics.
161 (2011): S112-S119. PDF File.

"Type I Glycogen Storage Disease."
Association for Glycogen Storage Disease. Assoc. for
Glycogen Storage Disease, 10 Aug. 2014. Web. 11 Aug. 2014.