Patients suffering from Type I glycogen storage disease frequently develop hepatic tumors. Some of these were classified as carcinoma, with the majority of tumors representing benign adenomata. However, no evidence exists of malignant transformation of adenomata in these patients. Here, we describe the occurrence of a hepatocellular carcinoma in the adenomata-bearing liver of the elder of two sisters suffering from Type I glycogen storage disease at the age of 20 years, 6 years after the diagnosis had been made. Surprisingly, a-fetoprotein levels were normal throughout the entire course of this patient, whereas the younger sister had elevated levels despite the absence of malignant lesions. Thus, the clinical significance of a-fetoprotein remains unclear in both cases. Nocturnal feeding, although performed continuously over the 6 years after the diagnosis, had obviously failed to prevent the development of hepatic tumors in both patients.
Inborn hepatic glycogenosis is associated with the development of liver tumors (1). Although some of these tumors have been classified as carcinoma (1-5), the malignant potential of adenomata occurring in glycogenotic livers is poorly defined up to date. Apparently, such malignancies are rarely observed in the first decade of life and tend to develop with increasing age. In order to provide further insight into the important question of transformation of hepatic adenoma into carcinoma, we report on two siblings with glycogen storage disease Type Ia (GSD Ia). Both patients had multiple adenomata, but only one of them developed hepatic carcinoma.
CASE REPORTS
In 1978, two siblings of 12 and 16 years of age, respectively, were admitted for the treatment of severe hyperlipidemia and growth retardation. The diagnostic work-up, including histology, histochemistry and biochemical analysis of liver biopsies, revealed the existence of GSD Ia in both girls (Table 1). Metabolic abnormalities included low insulin (<20 pU per ml) and elevated glucagon levels (300 pg per ml), as characteristic for GSD I (6). Abdominal ultrasound showed hepatomegaly in both cases, with a tumorous mass in the left lobe of the younger girl's liver (Table 3).
Consequently, nocturnal intragastric feeding according to Greene et a1 (7) was started and continued until present. Under this treatment, nocturnal glucose levels ranged from 80 to 120 mg per dl as detected on regular follow-up controls. Serum