Studies on the hyperammonemia and amino acid disturbances in multiple myeloma

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Two patients with multiple myeloma who appeared to be producing ammonia are reported(Acta Haematol. 84 : 130-134, 1990). Both patients showed hyperammonemia and amino acid disturbances, such as a low Fischer ratio. One patient had Bence Jones protein(lambda)type myeloma and became comatose, but the hyperammonemia and disturbance of consciousness were improved by chemotheray for the myeloma. The other patient had IgA kappa type myeloma and somnolence and died of malignant pleurisy despite intensive chemotherapy. Autopsy of both cases, showed widespread multiple myeloma and an almost normal liver. A cell line(KHM-4)was established from a second patient (Internal Med. 31 : 339-343, 1992). Surface marker studies of KHM-4 cells showed that the cells were positive for cytoplasmic immunoglobulins(IgA kappa), HLA-DR, and T10. Secretion of ammonia by the KHM-4 cells was detected by the addition of L-glutamine and L-arginine into the culture medium of amino acid-free RPMI 1640. In the presence of L-glutamine, KHM-4 cells secreted a greater amount of ammonia than the T cell line, CEM. However, production of ammonia by L-arginine was not observed in other cell lines. These observation provide hyperammonemia and serum amino acid disturbances.