Case 2: 8 month-old Male with Abdominal Distention

Diagnosis

Glycogen Storage Disease, type 1

Discussion

Glycogen storage disorder type I is associated with elevated levels of lactic acid and acidosis
Hepatic glycogen storage disorders (type 0, III, VI, and IX) are characterized by ketosis and usually yield a beta-hydroxybutyrate level greater than 2.5 mmol/L. They will also typically present with hyperlipidemia and elevated liver function tests.
GSD type 1 is an autosomal recessive disorder caused by a defect in glucose-6-phosphatase (G6P).
- GSD type 1 is further sub-classified into GSD type 1a caused by a mutation(s) in G6PC gene encoding G6P and type 1b caused by mutation(s) in G6PT1 (SLC37A4) encoding G6P translocase.

The G6P dysfunction causes impaired gluconeogenesis resulting in glycogen accumulation, primarily in the liver, and hypoglycemia.

The histology demonstrated features characteristic for GSD, enlarged hepatocytes in a mosaic pattern lined by a prominent “plant-cell” like cell membrane.

Steatosis can be seen in livers with GSD type 1 but was not obvious in our cases. EM also demonstrated characteristic ultrastructure with abundant cytoplasmic glycogen that dislocated cell organelles to the periphery of the cells. The dislocated organelles along with the true cell membrane together made the “plant-cell” like appearance seen by light microscopy.

Given the histologic and ultrastructural findings, the biochemical testing was performed and the diagnosis of GSD type 1 was confirmed.

GSD type 1 is clinically the most severe form and the symptoms typically appear early in life (often in infancy). Early diagnosis and intervention are critical.

References

Phillips MJ, Poucell S, Patterson J, Valencia P. The Liver: an Atlas and Text of Ultrastructural Pathology. New York, NY: Raven Press Books, Ltd.; 1987.
Odze RD, Goldblum JR. Odze and Goldblum Surgical Pathology of the GI tract, Liver, Biliary Tract, and Pancreas. 3^rd ed. Philadelphia, PA: Elsevier Saunders; 2015
Jevon GP, Dimmick JE. Histopathologic approach to metabolic liver disease: Part 1. Pediatr Dev Pathol. 1998;1(3):179-99.
Hicks J, Wartchow E, Mierau G. Glycogen storage diseases: a brief review and update on clinical features, genetic abnormalities, pathologic features, and treatment. Ultrastruct Pathol. 2011;35(5):183-96.
Roy A, Finegold MJ. Biopsy Diagnosis of Inherited Liver Disease. Surg Pathol Clin. 2010;3(3):743-68.

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