Glycogen storage disease type I (GSD I), also known as Von Gierke disease, is an inherited disorder caused by deficiencies of specific enzymes in the glycogen metabolism pathway. It was first described by Von Gierke in 1929 who reported excessive hepatic and renal glycogen in the autopsy reports of 2 children. It comprises 2 major subtypes, GSD Ia and GSD Ib. In GSD Ia, there is a deficiency of enzyme glucose-6-phosphatase (G6Pase) which cleaves glycogen to glucose thus leading to hypoglycemia and lactic acidosis. Patients with GSD 1b have normal G6Pase enzyme activity but have a deficiency of the transporter enzyme, glucose-6-phosphate translocase (G6PT). Patients present with manifestations of hypoglycemia and metabolic acidosis typically around 3 to 4 months of age. In patients suspected of having the disease, genetic testing is the investigation of choice to confirm the diagnosis. Dietary treatment prevents hypoglycemia and improves the life expectancy of patients. However, to prevent long-term complications such as hepatic adenomas and renal failure, animal models of GSD I are being developed to study the disease more closely and develop new treatment strategies such as gene therapy.
Etiology:- GSD Ia results from mutations in the G6PC gene on chromosome 17q21 that encodes for the G6Pase-a catalytic subunit. GSD Ib results from mutations in the SLC37A4 gene on chromosome 11q23.3.
Epidemiology:- The incidence of GSD I in the overall population is 1/100,000 with GSD Ia and Ib prevalent in 80% and 20% respectively. The Ashkenazi Jewish population has a 5-times greater prevalence compared to rest of the population.
Patho physiology:- The enzyme G6Pase is primarily expressed in the liver, kidney, and intestine. It has its active site on the luminal side of the endoplasmic reticulum (ER). Glucose-6-phosphate translocase is responsible for translocating Glucose-6-phosphate (G6P) from the cytoplasm into the ER lumen. The complex of G6Pase and G6PT catalyzes the final step of both glycogenolysis and gluconeogenesis for glucose production. Deficiency of either causes an accumulation of glycogen and fat in the liver, kidney, and intestinal mucosa.
Histopathology:- The availability of gene sequencing makes liver biopsy unnecessary. However, a biopsy may be ordered by the gastroenterologist in view of hepatomegaly. Histological evaluation of the liver shows hepatocytes filled with glycogen that is periodic acid-Schiff positive and diastase sensitive.
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