Glycogen Storage Disease

 Results in different enzymatic defects in liver that are classified as glycogen storage disease (GSD) types 0, I, II, III, IV, VI, and IX


image Types I, III, and IX account for 80% of hepatic GSD


• Most forms autosomal recessive, except GSD IX, which is X-linked




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

• Prognosis variable based on type of GSD


Microscopic




• Histologic features not generally diagnostic of GSD
• Assess liver for mosaic pattern of hepatocytes, glycogenated nuclei, fatty change, and fibrosis

image Enlarged, pale-staining, swollen hepatocyte cytoplasm, and prominent cell membrane appearance

image Compression of sinusoids by expanded hepatocytes

image GSD 0 has decreased glycogen

image GSD IV has characteristic cytoplasmic inclusions

• Cirrhosis frequent in GSD IV and can occur in III and IX


Ancillary Tests




• Electron microscopy
image Lysosomal-bound glycogen for GSD II

image Fibrillar glycogen for GSD IV


Top Differential Diagnoses




• Glycogenic hepatopathy

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


image
Hepatocellular Carcinoma in GSD Ia
Reticulin stain highlights the abnormal architecture, loss of reticulin fibers image, and pseudorosette formation image in this hepatocellular carcinoma arising in a patient with glycogen storage disease (GSD) Ia.

image
Steatosis and Fibrosis in GSD Ia
Prominent large and small droplet fat as well as periportal fibrosis is depicted in this case of GSD Ia.

image
Enlarged Hepatocytes in GSD Ib
The findings in this case of GSD Ib are similar to those observed in GSD Ia. Pale, enlarged hepatocytes with inconspicuous sinusoids contain only a rare glycogenated nucleus image. Fatty change is more apparent in this focus.


TERMINOLOGY


Abbreviations




• Glycogen storage disease (GSD)


Synonyms




• Glycogenoses


ETIOLOGY/PATHOGENESIS


Inborn Error of Carbohydrate Metabolism




• Gene mutation causes deficiency of hepatic enzymes involved in glycogen synthesis, degradation, or regulation
image GSD I, II, III, IV, VI, and IX display increased hepatic glycogen

image GSD 0 is storage defect that results in decreased hepatic glycogen

• Types I, III, and IX account for 80% of hepatic GSD

• Most forms autosomal recessive, except GSD IX, which is X-linked


CLINICAL ISSUES


Presentation




• Hepatomegaly: GSD I, III, IV, VI, IX, and rarely in GSD II
image GSD VI also causes short stature and hyperlipidemia

• Hypoglycemia
image GSD Ia, Ib, III: Hypoglycemia in infancy due to inability to maintain steady blood glucose levels between feedings
– Profound hypoglycemia can result in seizures

image GSD 0: Hypoglycemia after short fasts, often in early childhood as feed intervals are extended

image Hypoglycemia mild in GSD VI and IX, rare in GSD IV; not feature of GSD II


Laboratory Tests




• Enzymatic activity assay in liver tissue
image GSD Ia, III, IV, VI, and IX

• DNA mutational analysis


Treatment




• Dietary intervention to prevent hypoglycemia, particularly for GSD 0 and I, also in GSD III
• Liver transplantation corrects primary hepatic enzyme defect

image Best treatment option for GSD IV; also has been performed for GSD I, III, and IV


Prognosis




• Variable based on type of GSD
image Some patients well controlled

image Can lead to life-threatening complications including liver, heart, and respiratory failure

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Apr 20, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Glycogen Storage Disease
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