Glycogen storage disease type 1B

Glycogenosis type 1B is an autosomal recessive metabolic disease affecting glycogen and is characterized by hepatomegaly, hypoglycemia, neutropenia and recurrent infections.

Our body stores sugar in the form of glycogen, mainly in the liver and muscles, and its synthesis and degradation is essential for regulating blood glucose levels. Glycogen storage diseases (GSD) are a group of metabolic disorders of which they are divided into different subtypes depending on the enzyme that is altered.

Glycogenosis type 1 (GSD-1) affects the enzyme glucose-6-phosphatase and is divided into subtypes 1A (most common), in which mutations occur in the G6PC1 gene coding for glucose-6-phosphatase, and subtype 1B, which is due to mutations in the SLC37A4 gene. The SLC37A4 gene encodes for a glucose-6-phosphatase transporter. Pathogenic variants in SLC37A4 render glucose-6-phosphatase unable to be transported to the site where it acts, thereby affecting glycogen metabolism.

The incidence of GSD-1B is approximately 1 case per 100,000 individuals.

Symptoms

The clinical picture is similar to that of glycogenosis due to glucose-6-phosphatase type 1A deficiency, but neutropenia (low neutrophil count) and neutrophil dysfunction are added, leading to recurrent infections.

It usually manifests in the first year of life with hypoglycemia and hepatomegaly (enlarged liver) due to glycogen accumulation. Hypoglycemias, which can be more or less severe, are 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.

Glycogenosis type 1 is associated with an increased risk of hepatic adenomas that may occur along with intrahepatic bleeding and acute anemia. In addition, in GSD-1B there is an increased predisposition to develop enterocolitis and inflammatory bowel disease. Other complications of GSD-1B include kidney enlargement or nephromegaly, hypertension and renal tubular dysfunction.

Disease management

The management of patients with GSD-1A and GSD-1B 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.

Anti-inflammatory drugs and granulocyte colony-stimulating factor treatment are used to relieve intestinal inflammation and reduce neutropenia (associated with recurrent infections). Drugs are also used to control hypertension and renal dysfunction.

Genes analyzed

SLC37A4

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.

Halligan R, White FJ, Schwahn B, et al . The natural history of glycogen storage disease type Ib in England: A multisite survey. JIMD Rep. 2021 Jan 24;59(1):52-59.

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.

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