Hepatocellular carcinoma in glycogen storage disease type Ia: A case series

Abstract

We present a series of 8 patients (6 males, 2 females) with hepatocellular carcinoma (HCC) and glycogen storage disease type Ia (GSD Ia). In this group, the age at which treatment was initiated ranged from birth to 39 years (mean 9.9 years). All patients but one were noncompliant with treatment. Hepatic masses were first detected at an age range of 13-45 years (mean 28.1 years). Age at diagnosis of HCC ranged from 19 to 49 years (mean 36.9 years). Duration between the diagnosis of liver adenomas and the diagnosis of HCC ranged from 0 to 28 years (mean 8.8 years, SD = 11.5). Two patients had positive hepatitis serologies (one hepatitis B, one hepatitis C). Alpha-fetoprotein (AFP) was normal in 6 of the 8 patients. Carcinoembryonic antigen (CEA) was normal in the 5 patients in which it was measured. Current guidelines recommend abdominal ultrasonography with AFP and CEA levels every 3 months once patients develop hepatic lesions. Abdominal CT or MRI is advised when the lesions are large or poorly defined or are growing larger. We question the reliability of AFP and CEA as markers for HCC in GSD Ia. Aggressive interventional management of masses with rapid growth or poorly defined margins may be necessary to prevent the development of HCC in this patient population.

Early, sustained efficacy of adeno-associated virus vector-mediated gene therapy in glycogen storage disease type Ia

“…It is possible that correction of G6Pase deficiency and cell survival in the liver would reduce the risk for hepatocellular cancer in GSD-Ia. 28 Affected G6Pase-KO mice receive therapy during infancy and grow four-to five-fold in weight subsequently. Given the hyperplasia of tissues such as the liver accompanying rapid growth of young mice, the loss of vector genome DNA could be related to cell division and the accompanying reduction of episomal AAV vector Correction of GSD-Ia with an AAV2/8 vector DD Koeberl et al DNA.…”

“…30 The gradual loss of double-stranded AAV2/8 vector genomes observed here and previously in the liver of normal mice, which was increased compared to other AAV serotypes, was not accompanied by the sharp decrease in transgene expression associated with a vigorous cellular immune response. 28,31,32 If AAV vector-mediated G6Pase expression gradually wanes following treatment of infants with GSD-Ia, these patients subsequently could receive a 'booster' AAV vector cross-packaged as an alternative AAV serotype because of absence of cross-neutralization by antibodies against different serotypes. 10,33-35 Liver-targeted gene therapy has great potential in GSD-Ia, because of the demonstrated efficacy of G6Pase replacement by liver transplantation.…”

Glycogen storage disease type III-hepatocellular carcinoma a long-term complication?

“…Patient 1 did not have adenomas at the time of HCC development and had a mildly elevated AFP at the time of advanced metastatic HCC. Transaminases and AFP therefore do not appear to be reliable markers of liver disease or HCC transformation in these patients similar to what has been noted in GSD I [16]. Other reports of patients with GSD III and HCC mention that all had mildly to grossly elevated AFP levels at the time of HCC diagnosis; however, AFP levels prior to diagnosis were not reported (Table 1).…”

“…The pathophysiologic mechanism of adenoma development is unclear, but appears to be related to metabolic rather than hormonal causes [15]. The relationship between good metabolic control and the appearance of adenomas in GSD I patients is unclear, although some reports suggest a lower incidence and even regression of the tumors in adequately treated patients [16,17].…”

Liver transplantation for adenomatosis: European experience

“…1 HCC Gordon-Burroughs et al (35) (2014) 1 HCC Fernandez-Vega et al (36) (2014) 1 No Patients with GSD IA Matern et al (14) (1999) 14 No Labrune (15) (2002) 1 HCC Lerut et al (13) (2003) 1 HCC Franco et al (37) (2005) 1 HCC Arikan et al (38) (2006) 13 No Davis and Weinstein (39) (2008) 4 No Reddy et al (16) (2009) 1 HCC Manzia et al (40) (2011) 2 HCC…”