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Hereditary orotic aciduria, a disorder of pyrimidine metabolism responsive to uridine therapy
906
Society for Pediatric Research
Generally, his course was smooth and uncomplicated. Dr. Curnen, we certainly considered the possibility that we were binding circulating pneumococcal polysaccharide with our antibody; however, as I mentioned in our paper, a patient with the nephrotic syndrome who had pneumococcal peritonitis was biopsied and we were not able to demonstrate pneumococcal antibody deposition in the glomeruli. We hope to biopsy other patients with known pneumococcal infections to test this further. In answer to Dr. Dorfman, we have not biopsied any patients with pneumococcal infections who did not have some evidence of renal disease. The patient with the idiopathic nephrotic syndrome and pneumococcal peritonitis whose kidney was tested with the pneumococcal antibodies had only minimal basement membrane thickening and was in a partial remission at the time of biopsy. Dr. Fink, we agree that demonstration of serum antibody levels would be valuable and plan to have this done. In answer to Dr. Wehrle, we had 4 patients in whom there was no glomerular binding of group A streptococcal antibody. Of these, one had a recent history of impetigo, one had a respiratory infection, one had a history of both, and one had no antecedent infection. Of the 56 patients showing deposition of the antisera to the streptococcal polysaccharide, 37 patients had prior skin infections, 11 had respiratory infections, and 8 patients had a history of both. Impetigo is very common in our area in the summer and fall. O t h e r than the patient described in this report, there were no proved pneumococcal infections in our series of patients with acute nephrosis although 10 patients had pneumococci cultured from the nose and throat. Dr. Drummond, the glomerular deposition of the streptococcal antibodies has been more diffuse and less nodular in distribution than the deposition of the a n t i - h u m a n gamma globulin in our patients. The pneumococcal antisera were also more diffuse in distribution than the gamma globulin within the glomeruli. The fluorescein-labeled group A streptococcal antibody was obtained from the Biological Reagents Section of the Communicable Disease Center in Atlanta and was prepared from serum obtained from rabbits immunized with whole cells of group A streptococci. The antisera were then specific against the capsular polysaccharide of the streptococcus.
3. Hereditary orotic aciduria, a disorder of pyrimidine metabolism responsive to uridine therapy Mary E. Haggard * and Lillian H. Lockh a r t , ~ U n i v e r s i t y of T e x a s M e d i c a l C e n t e r , Galveston, Texas
Introduced
by Charles W. Daesehner
November 1965
In 1959, Huguley and associates described a male infant with refractory megaloblastic anemia associated with orotic aciduria. A second infant with this disorder presenting with mental and physical retardation, a normocytic hypochromic anemia, leukopenia, and megaloblastic bone marrow unresponsive to the usual hematinics but partially responsive to prednisone has been identified. Serum folic acid, serum vitamin B1~, urinary excretion of formiminoglutamic acid, gastric acidity, BUN, hemoglobin eleetrophoresis, and leukocyte chromosomal analyses were all within normal limits. An episode of obstructive nephropathy due to the orotie aciduria (930 mg. per 24 hours) complicated his clinical course prior to oral uridine therapy, which resulted in hematologic remission, decreased excretion of orotic acid, and increased physical growth. The effect of uridine on intellectual and motor development has not yet been completely assessed. Absence of orotidylic decarboxylase activity in the erythrocytes of the patient and decreased levels in the ceils of the parents and a male sibling have been demonstrated. DISCUSSION DR. L o u i s K. DIAMOND, Children's Hospital, 300 Longwood Ave., Boston, Mass. It is very pleasing to hear of this finding in patients with what is generally called a mixed type of anemia, that is, a possible deficiency of both iron and folic acid. However, a few such patients whom I can recall did not respond to either medication and may have had the type of deficiency under discussion. I wonder, Dr. Haggard, if you have any explanation for the double reticulocyte peak when you gave your patient the uridine. Is it possible that prednisone had something to do with this ? DR. A. K. BROWN, University of Virginia School of Medicine, Charlottesville, Va. Would you describe the morphology of the leukocytes prior to therapy? Were the nuclei of the polymorphonuclear leukocytes hypersegmented ? What changes took place in the white cells after therapy? DR. HAGGARD. We have no explanation for the double reticulocyte peak observed in this patient. The prednisone therapy was withdrawn and hematologic relapse allowed to develop prior to uridine administration. It would seem unlikely, therefore, that the pattern of reticulocyte response with uridine was in any way related to prednisone. It is of interest, however, that both the child treated by Dr. Huguley with nucleotides prepared from yeast extract as well as Drs. Becroft and Phillips' patient treated with uridine appear to have responded with more than one reticulocyte peak. The initial monocytosis observed in our patient disappeared following steroid therapy and did not recur when the drug was withdrawn. Neutrophils with six- or seven-lobed nuclei were present in small numbers prior to therapy and were not seen following response to uridine.
Society for Pediatric Research
Generally, his course was smooth and uncomplicated. Dr. Curnen, we certainly considered the possibility that we were binding circulating pneumococcal polysaccharide with our antibody; however, as I mentioned in our paper, a patient with the nephrotic syndrome who had pneumococcal peritonitis was biopsied and we were not able to demonstrate pneumococcal antibody deposition in the glomeruli. We hope to biopsy other patients with known pneumococcal infections to test this further. In answer to Dr. Dorfman, we have not biopsied any patients with pneumococcal infections who did not have some evidence of renal disease. The patient with the idiopathic nephrotic syndrome and pneumococcal peritonitis whose kidney was tested with the pneumococcal antibodies had only minimal basement membrane thickening and was in a partial remission at the time of biopsy. Dr. Fink, we agree that demonstration of serum antibody levels would be valuable and plan to have this done. In answer to Dr. Wehrle, we had 4 patients in whom there was no glomerular binding of group A streptococcal antibody. Of these, one had a recent history of impetigo, one had a respiratory infection, one had a history of both, and one had no antecedent infection. Of the 56 patients showing deposition of the antisera to the streptococcal polysaccharide, 37 patients had prior skin infections, 11 had respiratory infections, and 8 patients had a history of both. Impetigo is very common in our area in the summer and fall. O t h e r than the patient described in this report, there were no proved pneumococcal infections in our series of patients with acute nephrosis although 10 patients had pneumococci cultured from the nose and throat. Dr. Drummond, the glomerular deposition of the streptococcal antibodies has been more diffuse and less nodular in distribution than the deposition of the a n t i - h u m a n gamma globulin in our patients. The pneumococcal antisera were also more diffuse in distribution than the gamma globulin within the glomeruli. The fluorescein-labeled group A streptococcal antibody was obtained from the Biological Reagents Section of the Communicable Disease Center in Atlanta and was prepared from serum obtained from rabbits immunized with whole cells of group A streptococci. The antisera were then specific against the capsular polysaccharide of the streptococcus.
3. Hereditary orotic aciduria, a disorder of pyrimidine metabolism responsive to uridine therapy Mary E. Haggard * and Lillian H. Lockh a r t , ~ U n i v e r s i t y of T e x a s M e d i c a l C e n t e r , Galveston, Texas
Introduced
by Charles W. Daesehner
November 1965
In 1959, Huguley and associates described a male infant with refractory megaloblastic anemia associated with orotic aciduria. A second infant with this disorder presenting with mental and physical retardation, a normocytic hypochromic anemia, leukopenia, and megaloblastic bone marrow unresponsive to the usual hematinics but partially responsive to prednisone has been identified. Serum folic acid, serum vitamin B1~, urinary excretion of formiminoglutamic acid, gastric acidity, BUN, hemoglobin eleetrophoresis, and leukocyte chromosomal analyses were all within normal limits. An episode of obstructive nephropathy due to the orotie aciduria (930 mg. per 24 hours) complicated his clinical course prior to oral uridine therapy, which resulted in hematologic remission, decreased excretion of orotic acid, and increased physical growth. The effect of uridine on intellectual and motor development has not yet been completely assessed. Absence of orotidylic decarboxylase activity in the erythrocytes of the patient and decreased levels in the ceils of the parents and a male sibling have been demonstrated. DISCUSSION DR. L o u i s K. DIAMOND, Children's Hospital, 300 Longwood Ave., Boston, Mass. It is very pleasing to hear of this finding in patients with what is generally called a mixed type of anemia, that is, a possible deficiency of both iron and folic acid. However, a few such patients whom I can recall did not respond to either medication and may have had the type of deficiency under discussion. I wonder, Dr. Haggard, if you have any explanation for the double reticulocyte peak when you gave your patient the uridine. Is it possible that prednisone had something to do with this ? DR. A. K. BROWN, University of Virginia School of Medicine, Charlottesville, Va. Would you describe the morphology of the leukocytes prior to therapy? Were the nuclei of the polymorphonuclear leukocytes hypersegmented ? What changes took place in the white cells after therapy? DR. HAGGARD. We have no explanation for the double reticulocyte peak observed in this patient. The prednisone therapy was withdrawn and hematologic relapse allowed to develop prior to uridine administration. It would seem unlikely, therefore, that the pattern of reticulocyte response with uridine was in any way related to prednisone. It is of interest, however, that both the child treated by Dr. Huguley with nucleotides prepared from yeast extract as well as Drs. Becroft and Phillips' patient treated with uridine appear to have responded with more than one reticulocyte peak. The initial monocytosis observed in our patient disappeared following steroid therapy and did not recur when the drug was withdrawn. Neutrophils with six- or seven-lobed nuclei were present in small numbers prior to therapy and were not seen following response to uridine.