GLYCOGEN-STORAGE-DISEASE ASSOCIATED WITH NIEMANN-PICK DISEASE - HISTOCHEMICAL, ENZYMATIC, AND LIPID ANALYSES

A case of glycogen storage disease associated with multiple hepatic adenomas and Niemann-Pick disease is reported. Type LA glycogen disease was diagnosed soon after birth in a female patient, and she was treated at our clinic. At the age of 12 yr, the patient was found to have a hepatic tumor, which was surgically extirpated. Histological examination showed that the tumor was a hepatocellular adenoma. Increasing hepatomegaly and jaundice were noted when the patient was 18 yr of age. She died of pneumonia and cardiac tamponade at the age of 19. The liver weighed 3310 g, and showed severe jaundice and many nodules measuring up to 8 cm in diameter. These nodules were composed of mature hepatocytes without atypia and were diagnosed as hepatocellular adenomas. In addition, many adenomatous lesions were found at the microscopical level. The spleen weighed 1310 g, and showed two small infarctions at the upper part. A histological examination showed a diffuse infiltration of large foamy cells in the splenic red pulp. These cells were 20 to 100 mu m in diameter and weakly positive for periodic acid-Schiff (PAS) staining, positive for lipid staining with Sudan black B, and positive for Pearce's phospholipid staining. Electron microscopy showed many lamellar bodies in the cytoplasm that were characteristic of Niemann-Pick disease. These foamy cells were also found in liver, bone marrow, lymph nodes, kidneys, and lungs. A lipid analysis using thin-layer chromatography showed that, compared to normal spleen tissue, there was a marked increase in cholesterol, phosphatidyl ethanolamine, phosphatidyl choline (lecithin), and sphingomyelin, and a slight increase in free fatty acids and cholesterol ester. Sphingomyelinase activity assayed from the frozen liver tissue at the autopsy was depressed by 76%, compared to the control. These data were in agreement with the expected findings in Niemann-Pick disease.