Von Gierke disease
Von Gierke disease, also known as glycogen storage disease type I, is a rare inherited condition characterized by the inability to convert glycogen into glucose due to the absence of the enzyme glucose-6-phosphatase (G6P). There are two main types: Type Ia, caused by a deficiency of G6P, and Type Ib, resulting from a lack of G6P translocase. This autosomal recessive disorder predominantly affects individuals of Ashkenazi Jewish descent, with an incidence of about one in 20,000 births in that population compared to one in 100,000 overall.
Symptoms typically manifest shortly after birth and may include irritability, seizures, and lethargy. Without treatment, the disease can lead to severe hypoglycemia, which can be life-threatening. Diagnosis involves evaluating blood glucose and other metabolic markers, alongside genetic testing. Treatment focuses on managing diet, emphasizing high starch and glucose intake while avoiding other sugars that require G6P for metabolism.
Although there is no cure, early detection and dietary management can help mitigate some complications, which may include seizures, kidney issues, and potential liver transplants in severe cases. Regular monitoring and patient education about recognizing hypoglycemic episodes are essential for improving quality of life for those affected.
Von Gierke disease
ALSO KNOWN AS: Glycogen storage disease type I; von Gierke’s disease
DEFINITION Von Gierke disease is a rare inherited glycogen storage disease. It is characterized by the inability to break down glycogen into glucose because of the absence of the enzyme glucose-6-phosphatase (G6P). There are two types of von Gierke disease: Ia and Ib. Type Ia is caused by lack of G6P, and type Ib is caused by the lack of G6P translocase, the main transporter substance for G6P.
Risk Factors
Von Gierke disease is an autosomal recessive trait that requires that both parents pass on the mutations. An estimated 80 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 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 in Pediatric Discovery, 118 mutations had been identified as of May 2023. 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, 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 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.
Parikh, Nirzar S., and Rajni Ahlawat. "Glycogen Storage Disease Type I." StatPearls, 8 Aug. 2023, www.ncbi.nlm.nih.gov/books/NBK534196/. Accessed 9 Sept. 2024.
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.
"Von Gierke Disease." Medline Plus, 24 Apr. 2023, medlineplus.gov/ency/article/000338.htm. Accessed 9 Sept. 2024.
Zhong, Jiamin. "Glycogen Storage Disease Type I: Genetic Etiology, Clinical Manifestations, and Conventional and Gene Therapies." Pediatric Discovery, 24 July 2023, doi.org/10.1002/pdi3.3. Accessed 10 Sept. 2024.