Glycogen storage disease type 1A (Von Gierke Disease)

Glycogenosis type 1A is an autosomal recessive metabolic disease that affects the production of glucose from glycogen. It leads to abnormal glycogen accumulation and low blood glucose levels, which can result in hypoglycemic seizures and severe acidosis.

Glycogen storage diseases (GSD) are a group of inherited genetic disorders. In this type of metabolic diseases, glycogen (which is the storage form of sugar in our body) is synthesized or degraded incorrectly. They mainly affect the liver and muscles which are the main sites of glycogen storage.

Glycogenosis type 1A (GSD-1A), also known as Von Gierke disease, accounts for 90% of all cases of GSD. GSD-1A is due to deficiency of the enzyme glucose-6-phosphatase, which is involved in glycogenolysis, a metabolic process in which glucose is released from glycogen. This causes abnormal amounts of glycogen to accumulate in certain tissues and low blood sugar.

The prevalence of GSD-1A is 1 case per 100,000 individuals, being more common in the Ashkenazi Jewish population.

Symptoms

This disorder manifests in the first year of life with hypoglycemia and hepatomegaly (enlarged liver) due to glycogen accumulation. Hypoglycemia, which can be more or less severe, is accompanied by lactic acidosis and hyperlipemia, which includes both elevated triglycerides and cholesterol.

Hyperuricemia or excess of uric acid in the blood is also frequent, as a consequence of increased purine metabolism and renal insufficiency.

Type 1 glycogenosis is associated with an increased risk of hepatic adenomas which may occur along with intrahepatic bleeding and acute anemia.

Assessment of glucose-6-phosphatase activity in the liver and the presence of glycogen aggregates in liver cells or hepatocytes is critical for diagnosis.

Disease management

The management of patients with GSD-1A focuses on controlling blood glucose levels and preventing metabolic derangements as well as long-term complications. Special diets are available for this purpose, such as corn starch therapy and diets rich in complex carbohydrates in which fruits are restricted. Frequent feeding is also recommended, and in the case of infants and children, continuous nasogastric tube feeding can be used. Supplements are used to complement the deficiencies caused by the restrictions of some foods such as calcium, vitamin D and multivitamin complexes with minerals, iron and zinc. A multidisciplinary team specialized in metabolic diseases is required.

Genes analyzed

G6PC1

Bibliography

Bali DS, El-Gharbawy A, Austin S, et al . Glycogen Storage Disease Type I. 2006 Apr 19 [updated 2021 Oct 14]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022.

Kishnani PS, Austin SL, Abdenur JE, et al . Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. Genet Med. 2014 Nov;16(11):e1.

Niba ETE, Wijaya YOS, Awano H, et al . DBS Screening for Glycogen Storage Disease Type 1a: Detection of c.648G>T Mutation in G6PC by Combination of Modified Competitive Oligonucleotide Priming-PCR and Melting Curve Analysis. Int J Neonatal Screen. 2021 Nov 16;7(4):79.