Phyllis M. Madigan

Routine Newborn Screening for Histidinemia: Clinical and Biochemical Results

Abstract Routine Chromatographic screening of filter-paper urine specimens identified histidinemia in 20 newborn infants, or 1:20,000 in a screened population of 400,488. This relatively high incid...

Arginase Deficiency in Macaca fascicularis . I. Arginase Activity and Arginine Concentration in Erythrocytes and in Liver

Extract: We have found a genetic trait of arginase deficiency in erythrocytes (RBC) of Macaca fascicularis (crabeater macaque). Measurements of arginase activities and arginine concentrations in RBC, and information derived from breeding experiments indicated that arginase activities in RBC are 12.59 mmoles/g hemoglobin (Hb)/hr (range: 8.36–15.24) in normal monkeys, 4.40 mmoles/g Hb/hr (sd ± 2.37) in hetero-zygotes for this trait, and less than 0.05 mmoles/g Hb/hr in homozygotes for this trait. Concentrations of arginine in erythrocytes are less than 0.01

Results of a screening method for free amino acids II. Urine

mUmoles/ml packed cells in both normal and heterozygous monkeys, and 0.975

Cystathioninuria and homocystinuria

mUmoles/ml packed cells (sd ± 0.556) in homozygous monkeys.There are no significant differences in plasma amino acids and hepatic arginase activity in any animal.Speculation: Study of arginase activity in RBC will be expanded to include a large number of monkeys in order to determine the incidence of arginase deficiency in RBC in this species. The possibility of using these monkeys as an animal model for study of human disease arginase deficiency (e.g., genetic engineering) will be explored.

A rapid procedure for the determination of phenyl-alanine and tyrosine from blood filter paper specimens☆

Summary o 1. A method is described for general aminoacid analysis of urine impregnated into filter paper. 2. The method has been used to test over 15,000 specimens since January, 1966. 3. The entire program involves cooperation between a large state publichealth laboratory and a medical center. This cooperation has proven to be very successful. 4. Cystinuria, Hartnup disease, histidinemia, hyperglycinuria, and maternalphenylketonuria are among the disorders detected by this program.

MASSACHUSETTS METABOLIC DISORDERS SCREENING PROGRAM. I. TECHNICS AND RESULTS OF URINE SCREENING

Three circumstances prompted us to reexamine the relationship between abnormal cystathionine accumulation and possible homocystinuria resulting from this condition: (a) discovery of an infant girl with apparently alternating massive cystathioninuria and homocystinuria; (b) the presence of homocystinuria in some, but not all, previously reported cases of cystathioninuria probably due to gamma-cystathionine deficiency; and (c) the recent demonstration that mammalian cystathionine beta-synthase can cleave cystathionine to homocysteine. The following conclusions were reached: (a) Homocystine may arise as a result of bacterial contamination of a urine sample initially containing cystathionine, but not homocystine. (b) After a methionine load, a cystathioninuric patient may excrete readily detected amounts of homocystine. (c) However, homocystinuria is not a necessary concomitant of even massive cystathioninuria. These findings and some of their implications are briefly discussed.

Hypermethioninemia With Other Hyperaminoacidemias: Studies in Infants on High-Protein Diets

Abstract A method is described for rapid analysis of phenylalanine and tyrosine using eluates of whole blood that has been impregnated into filter paper. This method employs semi-automated ion-exchange column chromatography (amino acid analyzer) and will yield reasonably accurate and consistent quantitative values for phenylalanine and tyrosine concentrations within two hours. The technique has significant value in rapidly confirming the presence of increased phenylalanine with or without a concomitant increase in tyrosine concentration in autoclaved or unautoclaved blood filter paper specimens. Thus phenylketonuria can be differentiated from hyperphenylalaninemia due to tyrosinemia within hours after the initial identification of an elevated phenylalanine concentration by a screening method such as the Guthrie test. In addition, further evaluations of phenylalanine and tyrosine concentrations can be facilitated in infants on whom only blood filter paper specimens are obtainable.