Glycogen storage disease I and hepatocellular tumours

From 50 published cases of hepatocellular adenoma (HCA) in glycogen storage disease, type I (GSD I) some characteristic features may be deduced: 1. The male:female ratio was 2:1. This sharply contrasts to HCA of other origin which shows a strong female preponderance. 2. The histology of adenomas largely corresponded to other adenomas, except for the appearance of Mallory bodies, accompanied by neutrophilic inflammation and a peculiar lamellar fibrosis. This observation is of particular interest because Mallory bodies have so far not been described in adenomas but are a well established feature in hepatocellular carcinoma of any aetiology. 3. Adenomas had a tendency to regress after continuous nocturnal intragastric feeding, although not all cases responded favourably. 4. Ten cases of hepatocellular carcinoma (HCC) are recorded in GSD I in literature, whereby in half of them transition from HCA into HCC seems likely. 5. The similarity in clinical presentation and evolution with oestrogen-induced tumours is striking. Pathogenesis of adenoma formation in GSD I is not understood. Experimental evidence and the clinical observation of regression after correction of the metabolic imbalance suggest three possible candidate mechanisms: (1) a glucagon/insulin imbalance; (2) cellular glycogen overload; and (3) proto-oncogene activation. Evidence in favour of these three mechanisms from experimental studies and observations in humans are briefly reviewed.