Glycogen Storage Diseases



Glycogen Storage Diseases


Grace E. Kim, MD





Key Facts


Etiology/Pathogenesis



  • Inborn error of carbohydrate metabolism caused by gene mutations in proteins involved in glycogen synthesis, degradation, or regulation



    • Results in different enzymatic defects in liver that are classified as GSD types 0, I, II, III, IV, VI, and IX


    • 80% of hepatic GSD is types I, III, and IX


Clinical Issues



  • Most patients present with hepatomegaly and hypoglycemia


  • Increased incidence of hepatic adenoma and hepatocellular carcinoma in GSD I and also GSD III


  • Liver transplantation corrects primary hepatic enzyme defect and is used primarily for GSD IV


Microscopic Pathology



  • Assess liver for mosaic pattern of hepatocytes, glycogenated nuclei, fatty change, and fibrosis



    • GSD 0 has decreased glycogen


    • GSD IV has characteristic cytoplasmic inclusions


  • Cirrhosis occurs frequently in GSD IV and can occur in III and IX


Ancillary Tests



  • Lysosomal-bound glycogen for GSD II


  • Fibrillar amylopectin for GSD IV


Top Differential Diagnoses



  • Glycogen hepatopathy


  • Other entities with ground-glass cytoplasm






The mosaic pattern results from swollen hepatocytes compressing the sinusoids in this case of GSD Ia. The cell membranes are accentuated, and prominent glycogenated nuclei image are seen.






Reticulin stain highlights the abnormal architecture, loss of reticulin fibers image, and pseudorosette formation image in this hepatocellular carcinoma arising in a patient with GSD Ia.


TERMINOLOGY



Abbreviations



  • Glycogen storage diseases (GSDs)


Synonyms



  • Glycogenoses


ETIOLOGY/PATHOGENESIS


Inborn Error of Carbohydrate Metabolism



  • Gene mutation in proteins involved in glycogen synthesis, degradation, or regulation



    • Hepatic enzyme deficiency



      • GSD types 0, I, II, III, IV, VI, and IX


      • 80% of hepatic GSDs are types I, III, and IX


    • Abnormal concentration or structure of glycogen



      • GSD 0 results in decreased hepatic glycogen


      • Remaining types of GSD display increased hepatic glycogen


  • Inherited as autosomal recessive trait



    • Exception is GSD IX (X-linked disorder)


CLINICAL ISSUES


Presentation



  • Hepatomegaly



    • Occurs in GSD I, III, IV, VI, and IX


    • Rarely in GSD II


    • Not in GSD 0


  • Hypoglycemia



    • Occurs in GSD 0, I, and III


    • Mild in GSD VI and IX


    • Rarely in GSD IV


    • Not in GSD II


Laboratory Tests



  • Confirmation of diagnosis



    • Enzymatic assay on liver



      • GSD 0, I, II, III, VI, and IX


    • DNA mutation analysis



Treatment



  • Options, risks, complications



    • Increased incidence of hepatocellular neoplasia



      • Hepatic adenoma is frequent in GSD I and can occur in GSD III


      • Hepatocellular carcinoma occurs in GSD I and is reported in GSD III


    • GSD Ib has been associated with Crohn-like disease



      • Granulomatous colitis


      • Responds to inflammatory bowel disease treatment regimen


    • Dietary intervention



      • Prevents hypoglycemia, particularly for GSD 0 and I, less stringent in GSD III


  • Surgical approaches



    • Liver transplantation corrects primary hepatic enzyme defect



      • Has been performed for GSD I, III, and IV


      • Best treatment option for GSD IV if classic progressive liver disease


Prognosis



  • Variable based on type of GSD



    • GSD II (infantile form) usually results in death in 1st year of life


    • GSD IV (classic hepatic form) has rapid disease progression with liver failure at 3-5 years of age


MICROSCOPIC PATHOLOGY


Histologic Features



  • Not generally diagnostic of GSD



    • Exception is characteristic cytoplasmic inclusion in GSD IV



      • Stored material is amylopectin not glycogen


      • Weakly basophilic to colorless inclusion, retracts from surrounding cytoplasm



      • PAS positive and partially digested on PAS-D


  • Mosaic architecture



    • In GSD I, III, VI, and IX


    • Attributed to enlarged, pale-staining, swollen hepatocytes


    • Compression of sinusoid by expanded hepatocyte cytoplasm


    • Excess glycogen is PAS positive, PAS-D negative



      • Glycogen may wash out with formalin processing


      • Glycogen can be retained with alcohol fixation


  • Fibrosis



    • Initially in periportal region


    • GSD III, IV, VI, IX; may occur in GSD I



      • Mild fibrosis in GSD III


      • Cirrhosis can occur in GSD III (long-term survivors) and IX


      • Frequently progresses to cirrhosis in GSD IV


  • Features of hepatocytes



    • Glycogenated nuclei



      • In GSD I (prominent) and III (less prominent)


    • Thickened cytoplasmic membrane



      • Resulting from organelles at periphery of cytoplasm


  • Cytoplasmic lipid in all GSDs



    • More pronounced in GSD I

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Glycogen Storage Diseases

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