- Email: [email protected]
Trypsinogen deficiency disease
Volume65
Number 6 Part 2
both types of cells. The larger one showed 69 chromosomes a n d an X X Y constitution. The smaller ones had 46 chromosomes and an XY constitution. The triploid line consistently demonstrated a triplication for each autosome, while the diploid line had a normal balanced set of chromosomes. When tissue culture samples were stained with cresyl violet, 39 cells showed a positive sex chromatin mass out of 300 cells with large nuclei. Only 2 out of 300 cells with small nuclei were positive. In tissue culture the triploid cells did not appear to be at a disadvantage.
43. TryDsinogen deficiency disease Philip L. Townes, University of Rochester School of Medicine and Dentistry, Rochester, N. Y.
This report concerns a male infant found to have complete trypsinogen deficiency. The infant presented at 8 weeks of age with severe hypoproteinemia and no weight gain. Despite adequate intake, he lost 25 per cent of his weight during a 6 week period in the hospital and became too moribund to feed. Intravenous feeding with Lipomul and Amigen halted weight loss. Oral feedings of casein hydrolysate (Nutramigen) resulted in prompt weight gain. Within 3 weeks the lost weight was regained and serum proteins were normal. In the next 60 days, weight was almost doubled. A detailed nitrogen balance study at this time revealed a fecal loss of 18 per cent of ingested nitrogen on Nutramigen and a 70 per cent loss on intact casein (Similac). Sweat electrolytes, polyvinylpyrrolidone I TM, and all fat and carbohydrate absorption studies were normal. Duodenal juice was of normal color, pH, and viscosity. Lipase and amylase were normal, but there was no tryptic activity (Andersen-Early method). Duodenal biopsy was normal. Repeat duodenal intubation at 11 months (22 pounds) revealed no trypsin, ehymotrypsin, or carboxypeptidase activity when assayed with specific synthetic substrates. Addition of trypsin to the juice resulted in activation of chymotrypsinogen and procarboxypeptidase, but trypslnogen was absent. The primary defect, absence of trypsinogen, results in absence of trypsin, which in turn is essential for activation of chymotrypsinogen and procarboxypeptidase. Thus, the single enzyme deficiency results functionally in a triple enzyme deficiency. An unloading defect of the pancreas was excluded by a secretin-pancreozymin test. Family studies suggest that a deceased infant sib had the same disease. This study indicates that complete trypsinogen deficiency is an inborn error of metabolism, responds well to dietary management, and probably follows an autosomal recessive pattern of inheritance.
Abstracts
1 099
HEMATOLOGY
44. Physiology of erythroDoietln: Relationshi D of bone marrow activity to cyclic changes in levels of erythropoietin N. Shore, ~ G. Higgins, '~ N. Movassaghi, ~ and D. Hammond, University of Southern California School of Medicine and Childrens Hospital of Los Angeles, Los Angeles, Calif. Evidence from studies of patients with chronic anemia suggests that utilization of erythropoietin (EP) depends upon erythroid marrow activity. The present study proposes t h a t there is cyclic utilization of EP by the erythroid marrow. Serum and urine EP determinations and bone marrow aspirates were obtained serially during a prolonged aplastic crisis and recovery in a patient with sickle cell anemia. EP was measured by Fe s9 incorporation into circulating erythrocytes of the polyeythemic mouse. During the phase of erythroid marrow aplasia, serum and urine EP was elevated. When erythroid marrow hyperplasia ensued, serum and urine EP fell to normal control values. Following the initial fall of EP, a secondary rise in serum and urine EP occurred. Subsequent decrease in EP activity was associated with a rise in hemoglobin. The initial EP elevation is due to the presence of anemia and failure of EP utilization by an aplasfic marrow. T h e decrease of EP activity at the time of marrow hyperplasia, but prior to any change in hemoglobin, implies utilization of EP by the erythroid marrow. The secondary rise and subsequent fall of EP suggest that there is cyclic utilization of EP by the hyperplastie erythroid marrow. The final persistent low levels of EP may reflect the decreased production of EP because of the rise of hemoglobin.
45. The occurrence of the i antigen and elevated fetal hemoglobin in hemopoietic disorders Darcy W. O'Gonnan Hughes, e Park S. Gerald, Pat Corcoran, ~ and Louis K. Diamond, Children's Hospital Medical Center, Boston, Mass. The presence of the i antigen and fetal hemoglobin in cord blood and their decline during infancy have suggested an association between these findings. Further stimulus was provided by Giblett and co-workers, who detected the i antigen in thalassemia major and aplastlc anemia. This study was undertaken to correlate the presence of the i
Number 6 Part 2
both types of cells. The larger one showed 69 chromosomes a n d an X X Y constitution. The smaller ones had 46 chromosomes and an XY constitution. The triploid line consistently demonstrated a triplication for each autosome, while the diploid line had a normal balanced set of chromosomes. When tissue culture samples were stained with cresyl violet, 39 cells showed a positive sex chromatin mass out of 300 cells with large nuclei. Only 2 out of 300 cells with small nuclei were positive. In tissue culture the triploid cells did not appear to be at a disadvantage.
43. TryDsinogen deficiency disease Philip L. Townes, University of Rochester School of Medicine and Dentistry, Rochester, N. Y.
This report concerns a male infant found to have complete trypsinogen deficiency. The infant presented at 8 weeks of age with severe hypoproteinemia and no weight gain. Despite adequate intake, he lost 25 per cent of his weight during a 6 week period in the hospital and became too moribund to feed. Intravenous feeding with Lipomul and Amigen halted weight loss. Oral feedings of casein hydrolysate (Nutramigen) resulted in prompt weight gain. Within 3 weeks the lost weight was regained and serum proteins were normal. In the next 60 days, weight was almost doubled. A detailed nitrogen balance study at this time revealed a fecal loss of 18 per cent of ingested nitrogen on Nutramigen and a 70 per cent loss on intact casein (Similac). Sweat electrolytes, polyvinylpyrrolidone I TM, and all fat and carbohydrate absorption studies were normal. Duodenal juice was of normal color, pH, and viscosity. Lipase and amylase were normal, but there was no tryptic activity (Andersen-Early method). Duodenal biopsy was normal. Repeat duodenal intubation at 11 months (22 pounds) revealed no trypsin, ehymotrypsin, or carboxypeptidase activity when assayed with specific synthetic substrates. Addition of trypsin to the juice resulted in activation of chymotrypsinogen and procarboxypeptidase, but trypslnogen was absent. The primary defect, absence of trypsinogen, results in absence of trypsin, which in turn is essential for activation of chymotrypsinogen and procarboxypeptidase. Thus, the single enzyme deficiency results functionally in a triple enzyme deficiency. An unloading defect of the pancreas was excluded by a secretin-pancreozymin test. Family studies suggest that a deceased infant sib had the same disease. This study indicates that complete trypsinogen deficiency is an inborn error of metabolism, responds well to dietary management, and probably follows an autosomal recessive pattern of inheritance.
Abstracts
1 099
HEMATOLOGY
44. Physiology of erythroDoietln: Relationshi D of bone marrow activity to cyclic changes in levels of erythropoietin N. Shore, ~ G. Higgins, '~ N. Movassaghi, ~ and D. Hammond, University of Southern California School of Medicine and Childrens Hospital of Los Angeles, Los Angeles, Calif. Evidence from studies of patients with chronic anemia suggests that utilization of erythropoietin (EP) depends upon erythroid marrow activity. The present study proposes t h a t there is cyclic utilization of EP by the erythroid marrow. Serum and urine EP determinations and bone marrow aspirates were obtained serially during a prolonged aplastic crisis and recovery in a patient with sickle cell anemia. EP was measured by Fe s9 incorporation into circulating erythrocytes of the polyeythemic mouse. During the phase of erythroid marrow aplasia, serum and urine EP was elevated. When erythroid marrow hyperplasia ensued, serum and urine EP fell to normal control values. Following the initial fall of EP, a secondary rise in serum and urine EP occurred. Subsequent decrease in EP activity was associated with a rise in hemoglobin. The initial EP elevation is due to the presence of anemia and failure of EP utilization by an aplasfic marrow. T h e decrease of EP activity at the time of marrow hyperplasia, but prior to any change in hemoglobin, implies utilization of EP by the erythroid marrow. The secondary rise and subsequent fall of EP suggest that there is cyclic utilization of EP by the hyperplastie erythroid marrow. The final persistent low levels of EP may reflect the decreased production of EP because of the rise of hemoglobin.
45. The occurrence of the i antigen and elevated fetal hemoglobin in hemopoietic disorders Darcy W. O'Gonnan Hughes, e Park S. Gerald, Pat Corcoran, ~ and Louis K. Diamond, Children's Hospital Medical Center, Boston, Mass. The presence of the i antigen and fetal hemoglobin in cord blood and their decline during infancy have suggested an association between these findings. Further stimulus was provided by Giblett and co-workers, who detected the i antigen in thalassemia major and aplastlc anemia. This study was undertaken to correlate the presence of the i