Deficient activity of dephosphophosphorylase kinase and accumulation of glycogen in the liver.

Low activity of phosphorylase and increased concentration of glycogen were found in liver tissue from five children with asymptomatic hepatomegaly. In vitro activation of liver phosphorylase in these patients occurred at the rate of 10% or less of normal. Elimination of the defect by the addition of kinase that activates phosphorylase demonstrated the integrity of the phosphorylase enzyme and the deficient activity of dephophophosphorylase kinase. On the average, 60% of the phosphorylase enzyme of normal human liver was in the active form. Phosphorylase kinase of rabbit muscle activated phosphorylase of normal human liver to a final value that was significantly higher than the one obtained in the absence of muscle phosphorylase kinase. The ultrastructural examination of hepatic tissue from the five patients revealed increased amounts of glycogen. There was scarcity of endoplasmic reticulum. There was intercellular glycogen in continuity with the glycogen of the hepatocytes through breaks in their circumference. Lipid droplets with lucid areas in the form of needles and plates contained aggregates of glycogen. There were numerous lysosomes, some containing glycogen. Large vacuoles filled with glycogen and surrounded by a membrane were seen occasionally. The vacuoles might reflect the lysosomal pathway of glycogen degradation, since there was apparent fusion of such autophagic vacuoles with small vesicles resembling primary lysosomes.