Glycogenosis types Ia and Ib (GSD1, von Gierke disease) (Glycogen storage disease type Ia and 1b) - Genes G6PC and SLC37A4.

Glycogenosis are a group of inherited diseases caused by genetic deficiency or absence of the activity of some of the enzymes involved in the synthesis or degradation of glycogen. Glycogenosis type I, also known as von Gierke GSDI or disease, is caused by the accumulation of glycogen in the body cells. Glycogen accumulation in certain organs and tissues, especially the liver, kidneys and small intestine, alters its normal functional capacity.

Signs and symptoms of this disease usually appear about 3 or 4 months of age, when babies begin to sleep through the night and eat as often as newborns. Affected children may experience hypoglycemia, lactic acidosis, hyperuricemia and hyperlipidemia. As they grow, children with GSDI have thin arms and legs and short stature. An enlarged liver can be confused with a protruding abdomen. The kidneys can also be enlarged. Affected individuals may also have diarrhea and xantomas. Furthermore, people with GSDI can manifest delayed puberty, osteoporosis, gout, progressive renal failure, pulmonary hypertension and hepatic adenoma. Affected women may also have polycystic ovaries.

They described two types of GSDI, which differ in their signs and symptoms and genetic causes. These types are known as glycogenosis type Ia (GSDIa) and glycogenosis type Ib (GSDIb). While we have described two forms of GSDI originally called Ic and Id type, these types of variations are considered GSDIb. Some of the characteristic features of GSDIb may include neutropenia, inflammatory bowel disease and oral problems including caries, gingivitis, periodontal chronic disease, abnormal development of teeth and mouth ulcers. Neutropenia problems and oral are specific to people with GSDIb and usually are not seen in people with GSDIa.

Glycogenosis type I is due to mutations in the gene G6PC, located on the long arm of chromosome 17 (17q21) and in the SLC37A4 gene, the long arm of chromosome 11 (11q23.3). The gene mutations cause G6PC GSDIa while SLC37A4 gene mutations cause GSDIb. The proteins encoded by the SLC37A4 gene and G6PC, called glucose 6-phosphatase and glucose 6-phosphate translocase, respectively, act together to decompose the glucose 6-phosphate. The breakdown of this molecule produces glucose, which is the primary energy source for most cells in the body.

They have identified at least 85 mutations in the gene G6PC in people with type Ia glycogenosis (GSDIa) and more than 80 mutations in the SLC37A4 gene in those with glycogenosis type Ib (GSDIb). Mutations in genes SLC37A4 G6PC and inhibit effective breakdown of glucose 6-phosphate. Glucose 6-phosphate does not decompose glucose becomes glycogen and fat so that it can be stored within cells. Excess glycogen and fat stored inside a cell may be toxic. This accumulation causes damage to organs and tissues throughout the body, especially the liver and kidneys, leading to signs and symptoms of GSDI.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Glycogen types Ia and Ib, by complete PCR amplification of the exons of G6PC and SLC37A4, respectively, and subsequent sequencing genes.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).