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April 1957, Vol 93, No. 4 >
Article | April 1957

Phenylketonuria FREE

STANLEY W. WRIGHT, M.D.; GEORGE TARJAN, M.D.
[+] Author Affiliations

Submitted for publication Sept. 24, 1956; accepted Oct. 16.


AMA Am J Dis Child. 1957;93(4):405-419. doi:10.1001/archpedi.1957.02060040407009.
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Recently acquired knowledge and increased interest in the problems of mental retardation have prompted this presentation on phenylketonuria. Twenty-one patients are reported with a review of the literature. Phenylketonuria may well become a working model for the study of diseases in which psychological abnormalities and multiple biochemical aberrations are the result of a genetically determined enzyme deficiency.

History  The Norwegian biochemist Fölling first described phenylketonuria in 1934.1 He isolated and crystallized phenylpyruvic acid from the strikingly malodorous urines of two defective siblings. Later, he reported 10 similar patients, noting the lack of clear-cut physical characteristics, a tendency toward dermatoses, muscular rigidity, and an ape-like, or pithecoid, posture. Since phenylpyruvic acid was not found in the urine of normal persons, he related its presence to the mental retardation and named the disease "Imbecillitas Phenylpyruvica." Cases were identified in other European countries and America,2-4 and by 1954 Jervis found 513

REFERENCES

1 +
Fölling, A.:  Ueber Ausscheidung von Phenylbrenztraubensäure in den Harn als Stoffwechselanomalie in Verbindung mit Imbezillität , Ztschr. Physiol. Chem. 227:169, 1935;.
2 +
Penrose, L. S.:  Two Cases of Phenylpyruvic Amentia , Lancet 1:23, 1935;.
3 +
Jervis, G. A.:  Phenylpyruvic Oligophrenia: Introductory Study of 50 Cases of Mental Deficiency Associated with Excretion of Phenylpyruvic Acid , Arch. Neurol. & Psychiat. 38:944, 1937;.
4 +
Brügger, C.:  Die Ausscheidung von Phenylbrenztraubensäure im Urin von Schwachsinnigen , Schweiz. Arch. Neurol. u. Psychiat. 49:62, 1942;.
5 +
Jervis, G. A.:  Phenylpyruvic Oligophrenia (Phenylketonuria) , A. Res. Nerv. & Ment. Dis., Proc. 33:259, 1954;.
6 +
Cowie, V.:  Phenylpyruvic Oligophrenia , J. Ment. Sc. 97:505, 1951;.
7 +
Penrose, L. S.:  Phenylketonuria: A Problem in Eugenics , Lancet 1:949, 1946;.
8 +
Penrose, L. S.: Biology of Mental Defect , New York, Grune & Stratton, Inc., 1949;.
9 +
Cowie, V. A.:  Atypical Case of Phenylketonuria , Lancet 1:272, 1951;.
10 +
Harris, H.: An Introduction to Human Biochemical Genetics, Eugenics Laboratory Memoirs , 37, London, Cambridge University Press, 1953;.
11 +
Bates, R. M.:  Three Cases of Phenylpyruvic Oligophrenia , J. Ment. Sc. 85:273, 1939;.
12 +
Mautner, H., and Quinn, K. V.:  Phenylpyruvic Oligophrenia , Ann. paediat. 172:1, 1949;.
13 +
Woolf, L. I., and Vulliamy, D. G.:  Phenylketonuria with a Study of Effect upon It of Glutamic Acid , Arch. Dis. Childhood 26:487, 1951;.
14 +
Cowie, V. A., and Penrose, L. S.:  Dilution of Hair Colour in Phenylketonuria , Ann. Eugenics 15:297, 1951;.
15 +
Levy, S., and Perry, H. A.:  Phenylpyruvic Acid Factor in Mental Deficiency and Mental Illness , Am. J. Ment. Deficiency 54:73, 1949;.
16 +
Frazier, R. L.:  Phenylpyruvic Amentia: Report of an Institution Survey , Am. J. Ment. Deficiency 51:577, 1947;.
17 +
Benda, C. E.: Developmental Disorders of Mentation and Cerebral Palsies , New York, Grune & Stratton, Inc., 1952;.
18 +
Josephy, H.:  Phenylpyruvic Oligophrenia (Report on 16 Clinical Cases and 2 Autopsies) , Illinois M. J. 94:107, 1948;.
19 +
Cantor, S. J.:  Phenylpyruvic Oligophrenia, with Notes on New Case and Report of Laboratory Investigations in an Earlier Case , M. J. Australia 1:69, 1952;.
20 +
Warthen, R. O.; Tandeta, M., and Williams, J. M.:  Phenylpyruvic Oligophrenia: 2 Cases of Siblings , Am. J. Dis. Child. 78:759, 1949;.
21 +
Meldicott, R. W.:  Phenylpyruvic Oligophrenia , New Zealand M. J. 43:101, 1944;.
22 +
Penrose, L. S.:  Measurement of Pleiotropic Effects on Phenylketonuria , Ann. Eugenics 16:134, 1951;.
23 +
Penrose, L. S.:  Inheritance of Phenylpyruvic Amentia (Phenylketonuria) , Lancet 2:192, 1935;.
24 +
Jervis, G. A.:  Genetics of Phenylpyruvic Oligophrenia , J. Ment. Sc. 85:719, 1939;.
25 +
Munro, T. A.:  Phenylketonuria: Data on 47 British Families , Ann. Eugenics 14:60, 1949;.
26 +
Larson, C. A.:  An Estimate of the Frequency of Phenylketonuria in South Sweden , Folia hered. et path. 4:40, 1954;.
27 +
Fölling, A., and Closs, K.:  Über das Vorkommen von 1-Phenylalanin in Harn und Blut bei Imbecillitas phenylpyrouvica , Ztschr. physiol. Chem. 254:115-116, 1938;.
28 +
Brügger, C.:  The Elimination of Phenylpyruvic Acid by Mentally Deficient Individuals , Schweiz. med. Wchnschr. 73:967, 1943;
29 +
J. Ment. Sc. 92:269, 1946;.
30 +
Fölling, A.; Mohr, O. L., and Ruud, L.: Oligophrenia Phenylpyrouvica: A Recessive Syndrome in Man , Oslo, Dybwad, 1945;.
31 +
Cohen, P., and Kozinn, P. J.:  Phenylpyruvic Oligophrenia in Jewish Child , J. Pediat. 34:76, 1949;.
32 +
Fernandes, J. F.:  Phenylpyruvic Oligophrenia in the Dark-Skinned Person , Brasil-m éd. 64:225, 1950;
33 +
J. Ment. Sc. 97:855, 1951;.
34 +
Penrose, L. S.:  A Search for Linkage Between the A. B. O. Agglutinogens and Phenylketonuria , Am. J. Ment. Deficiency 50:4, 1945;.
35 +
Patients in Mental Institutions, Part 1, Public Institutions for Mental Defectives and Epileptics , U. S. Public Health Service Publication, No. 483, (Part 1) , 1952;.
36 +
Lerner, A. B.:  Metabolism of Phenylalanine and Tyrosine , in Advances in Enzymology , Edited by F. F. Nord, Vol. 14, New York, Interscience Publishers, Inc., 1953;, p. 73.
37 +
Knox, W. E.:  The Metabolism of Phenylalanine and Tyrosine , in Amino Acid Metabolism , Edited by W. D. McElroy and B. Glass, Baltimore, Johns Hopkins Press, 1955;.
38 +
Jervis, G. A.:  Phenylpyruvic Oligophrenia Deficiency of Phenylalanine-Oxidizing System , Proc. Soc. Exper. Biol. & Med. 82:514, 1953;.
39 +
Woolf, L. I.:  Excretion of Conjugated Phenylacetic Acid in Phenylketonuria , Biochem. J. 49:ix, 1951;.
40 +
Stein, W. H., Paladini, A. C., Hirs, C. H. W., and Moore, S.:  Phenylacetylglutamine as a Constituent of Normal Human Urines , J. Am. Chem. Soc. 76:2848, 1954;.
41 +
Armstrong, M. D.; Shaw, K. N. F., and Robinson, K. S.:  Studies on Phenylketonuria: II. The Excretion of o-Hydroxyphenylacetic Acid in Phenylketonuria , J. Biol. Chem. 213:797, 1955;.
42 +
Armstrong, M. D., and Shaw, K. N. F.:  Studies on Phenylketonuria: III. The Metabolism of o-Tyrosine , J. Biol. Chem. 213:805, 1955;.
43 +
Boscott, R. J., and Bickel, H.:  Detection of Some New Abnormal Metabolites in the Urine of Phenylketonuria, Scandinav . J. Clin. & Lab. Invest. 5:380, 1953;.
44 +
Boscott, R. J., and Bickel, H.:  Phenylalanine and Tyrosine Metabolism in Patients with Phenylketonuria , Biochem. J. 56:1, 1954;.
45 +
Jervis, G. A.:  Studies on Phenylpyruvic Oligophrenia: Position of Metabolic Error , J. Biol. Chem. 169:651, 1947;.
46 +
Delay, J.; Pichot, P.; Delbarre, F., and Taseel, J.:  L'oligophrénie phénylpyruvique; nouvelles observations , Bull. et mém. Soc. méd. hôp. Paris 64:669, 1948;.
47 +
(Cited by Cowie, V. A.: J. Ment. Sc. 97:505, 1951;.
48 +
Cowie, V. A.:  Galactose Tolerance Test in Phenylketonuria , J. Ment. Sc. 96:799, 1950;.
49 +
Pichot, D.; Delay, J., and Bertagna, L.: L'oligophrénie phénylpyruvique, Extrait Annales Médico-Psychologiques, No. 3, 1949.
50 +
V. A.: J. Ment. Sc. 97:505, 1951;.
51 +
Udenfriend, S., and Bessman, S. P.:  Hydroxylation of Phenylalanine and Antipyrine in Phenylpyruvic Oligophrenia , J. Biol. Chem. 203: 961, 1953;.
52 +
Weil-Malherbe, H., in Biochemistry of the Developing Nervous System , Edited by Waelsch, H., New York, Academic Press, Inc., 1955;, p. 427.
53 +
Harley-Mason, J., and Cromartie, R. I. T.: Formation of Monohydroxyindoles from Dihydroxyphenalanine, Proceedings of the Biochemical Society, Biochem. J. 51:xxiv, 1952.
54 +
Armstrong, M. D., and Robinson, K. S.:  On the Excretion of Indole Derivatives in Phenylketonuria , Arch. Biochem. 52:287, 1954;.
55 +
Jepson, J. B.:  Paper Chromatography of Urinary Indoles , Lancet 2:1009, 1955;.
56 +
Ferrari, V.; Campagnari, F., and Guida, A.:  Phenylpyruvic Oligophrenia: New Chemico Pathological Findings , Minerva med. 46:119, 1955;;
57 +
Abstract, J. A. M. A. 159:1160, 1955;.
58 +
Dent, C. E.: Personal Communication cited in Year Book of Pediatrics , 1955;-56, Chicago, The Year Book Publishers, Inc., p. 59.
59 +
Jervis, G. A.; Block, R. J.; Bolling, D., and Kanze, E.:  Chemical and Metabolic Studies on Phenylalanine: Phenylalanine Content of the Blood and Spinal Fluid in Phenylpyruvic Oligophrenia , J. Biol. Chem. 134:105, 1940;.
60 +
Borek, E.; Brecher, A.; Jervis, G. A., and Waelsch, H.:  Oligophrenia Phenylpyruvica; Constancy of Metabolic Error , Proc. Soc. Exper. Biol. & Med. 75:86, 1950;.
61 +
Block, R. J.; Jervis, G. A.; Bolling, D., and Webb, M.:  Chemical and Metabolic Studies on Phenylalanine: Amino Acid Content of Tissue Proteins of Normal and Phenylpyruvic Oligophrenic Individuals: Note on the Estimation of Phenylalanine , J. Biol. Chem. 134:567, 1940;.
62 +
Schrappe, O.:  Zur pathologischen Physiologie des Phenylbrenztraubensäure-Schwachsinns , Nervenarzt 23:175, 1952;.
63 +
Penrose, L. S., and Quastel, J. H.:  Metabolic Studies on Phenylketonuria , Biochem. J. 31:266, 1937;.
64 +
Dann, M.; Marples, E., and Levine, S. Z.:  Phenylpyruvic Oligophrenia: Report of Case in Infant with Quantitative Chemical Studies of Urine . J. Clin. Invest. 22:87, 1943;.
65 +
Dobriner, K.; Rhoads, C. P., and Lieberman, S.:  Spectroscopy as Applied to the Study of Phenylpyruvic Oligophrenia: Role of Nutritional Deficiency in Nervous and Mental Disease , Res. Nerv. & Ment. Dis. Proc. 22:158, 1943;.
66 +
Jervis, G. A.:  Studies on Phenylpyruvic Oligophrenia: Phenylpyruvic Acid Content of Blood , Proc. Soc. Exper. Biol. & Med. 81:715, 1953;.
67 +
Jervis, G. A.:  Metabolic Investigations on Case of Phenylpyruvic Oligophrenia , J. Biol. Chem. 126:305, 1938;.
68 +
Jervis, G. A.:  Excretion of Phenylalanine and Derivatives in Phenylpyruvic Oligophrenia , Proc. Soc. Exper. Biol. & Med. 75:83, 1950;.
69 +
Lepow, H.:  Phenylpyruvic Oligophrenia: A Clinical and Biochemical Study , Monatsschr. Psychiat. u. Neurol. 110:161, 1945;
70 +
J. Ment. Sc. 92:649, 1946;.
71 +
Snyderman, S. E.; Norton, P., and Holt, L. E., Jr.:  Effect of Tyrosine Administration in Phenylketonuria , Fed. Proc. 14:450, 1955;.
72 +
Meister, A.; Udenfriend, S., and Bessman, S. P.:  Diminished Phenylketonuria in Phenylpyruvic Oligophrenia After Administration of L-Glutamine, L-Glutamate or L-Asparagine , J. Clin. Invest. 35:619, 1956;.
73 +
Albanese, A. A.:  Colorimetric Estimation of Phenylalanine in Some Biological Products , J. Biol. Chem. 155:291, 1944;.
74 +
Block, R. J., and Bolling, D.:  Chemical and Metabolic Studies on Phenylalanine: The Nitration of Phenylalanine , J. Biol. Chem. 129:1, 1939;.
75 +
Udenfriend, S., and Cooper, J. R.:  Assay of L-Phenylalanine as Phenylethylamine After Enzymatic Decarboxylation; Application to Isotope Study , J. Biol. Chem. 203:953, 1953;.
76 +
Prescott, B. A.; Borek, E.; Brecher, A., and Waelsch, H.:  Studies on Oligophrenia Phenylpyruvica; Microbiological Determination of L-and D-Phenylalanine and of Phenyllactic Acid , J. Biol. Chem. 181:273, 1949;.
77 +
Armstrong, M. D.: Personal communication to the authors.
78 +
Berry, J. P., and Woolf, L. I.:  Estimation of Phenylpyruvic Acid , Nature , London 169:202, 1952;.
79 +
Kondritzer, A. A.:  Precipitation Pattern of Serum Proteins in Phenylpyruvic Oligophrenia , Proc. Soc. Exper. Biol. & Med. 44:404, 1940;.
80 +
Brown, D. M.; Armstrong, M. D., and Smith, E. L.:  Studies on Phenylketonuria: Serum Proteins in Phenylketonuria , Proc. Soc. Exper. Biol. & Med. 89:367, 1955;.
81 +
Pauling, L.: Personal communication to the authors.
82 +
Pugh, C. E. M.:  The Use of Creatine-Creatinine Ratio , J. Ment. Sc. 86:240, 1940;.
83 +
Himwich, H. E., and Fazekas, J. F.:  Cerebral Metabolism in Mongolian Idiocy and Phenyl-Pyruvic Oligophrenia , Arch. Neurol. & Psychiat. 44:1213, 1940;.
84 +
Weil-Malherbe, H.:  Blood Adrenalin and Intelligence , in Biochemistry of the Developing Nervous System , Edited by Waelsch, H., New York, Academic Press, Inc., 1955;.
85 +
Kreezer, G. L.:  Research in Progress upon the Electroencephalogram in Mental Deficiency . Proc. Am. Ment. Deficiency 63:120, 1939;
86 +
Abstract, J. Ment. Deficiency 86:1123, 1940;.
87 +
Fois, A.; Rosenberg, C., and Gibbs, F. A.:  The Electroencephalogram in Phenylpyruvic Oligophrenia, Electroencephalog . & Clin. Neurophysiol. 7:569, 1955;.
88 +
Gibbs, F. A., and Gibbs, E. L.:  Phenylpyruvic Amentia , in Atlas of Electroencephalography , Reading, Mass., Addison-Wesley Publishing Company, Inc., 1950;.
89 +
Alvord, E. C., Jr.; Stevenson, L. D.; Vogel, F. S., and Engle, R. L., Jr.:  Neuropathological Findings in Phenyl-Pyruvic Oligophrenia (Phenylketonuria) , J. Neuropath. & Exper. Neurol. 9:298, 1950;.
90 +
Penrose, L. S.:  Peripheral Nerve Tumors in Case of Phenylketonuria , Lancet 1:572, 1939;.
91 +
Corsellis, J. A. N.:  Pathological Report of Case of Phenylpyruvic Oligophrenia , J. Neurol. Neurosurg. & Psychiat. 16:139, 1953;.
92 +
Bickel, H.; Gerrard, J., and Hickmans, E. M.:  Influence of Phenylalanine Intake on Chemistry and Behavior of a Phenylketonuric Child , Acta. paediat. 43:64, 1954;.
93 +
Bickel, H.; Boscott, R. J.; Gerrard, J., and Waelsch, H.:  Observations on the Biochemical Error in Phenylketonuria and Its Dietary Control , in Biochemistry of the Developing Nervous System , Edited by H. Waelsch, New York, Academic Press, Inc., 1955;.
94 +
Woolf, L. I.; Griffiths. R., and Moncrieff, A.:  Treatment of Phenylketonuria with a Diet Low in Phenylalanine , Brit. M. J. 2:57, 1955;.
95 +
Armstrong, M. D., and Tyler, F. H.:  Studies on Phenylketonuria: Restricted Phenylalanine Intake in Phenylketonuria , J. Clin. Invest. 34:565, 1955;.
96 +
Horner, F. A., and Streamer, C. W.:  Effect of a Phenylalanine-Restricted Diet on Patients with Phenylketonuria , J. A. M. A. 161:1628, 1956;.
97 +
Bosma, J. F.; Low, N. L.; Armstrong, M. D.; Tyler, F. H.; Madsen, J. A., and Carlisle, J. W.:  Clinical Effects of Phenylalanine Restrictive Diet in Phenylketonuria , Presented at Society for Pediatric Research, Buck Hill Falls, Pa. , 1956;.
98 +
Cares, R. M.:  Absence of Phenylketonuria in Adult Psychotics: A Survey of 4246 Inmates of a State Mental Hospital , Am. J. Psychiat. 112: 938, 1956;.
99 +
Dancis, J., and Balis, M. E.:  A Possible Mechanism for Disturbance in Tyrosine Metabolism in Phenylpyruvic Oligophrenia , Pediatrics 15:63, 1955;.
100 +
Hsia, D. V., and Driscoll, K.:  Detection of the Heterozygote in Phenylketonuria , Presented at the Society for Pediatric Research, Buck Hill Falls, Pa. , 1956;.
101 +
Lorcomb, J. W.:  Phenylketonuria and the Congenitally Deaf , J. Pediat. 14:348, 1939;.
102 +
Udenfriend, S.; Titus, E.; Weissbach, H., and Peterson, R. E.:  Biogenesis and Metabolism of 5-Hydroxyindole Compounds , J. Biol. Chem. 219:335, 1956;.
103 +
Brodie, B. B.; Pletscher, A. B., and Shore, P. A.:  Evidence that Serotonin Has a Role in Brain Function , Science 122:968, 1955;.
104 +
McGeer, P. L.; McGeer, E. G., and Gibson, W. C.:  Aromatic Excretory Pattern of Schizophrenics , Science 123:1029, 1956;.
105 +
McGeer, P. L.; McGeer, E. G., and Boulding, J. E.:  Relation of Aromatic Amino Acids to Excretory Pattern of Schizophrenics , Science 123:1078, 1956;.
106 +
Boscott, J. R., in Biochemistry of the Developing Nervous System , Edited by H. Waelsch, New York, Academic Press, Inc., 1955;, p. 428.
107 +
Larson, C. A.: The Absence of Phenylketonuria in 8220 Individuals not Known to be Mental Defectives, Novant'anni Delle Leggi Mendeliane , Rome, Instituto Gregorio Mendel, 1956;, p. 311.
108 +
Crowe, F. W., and Schull, W. J.:  Phenylketonuria: Studies in Pigment Formation , Folia hered. et path. 1:259, 1952;.
109 +
Jervis, G. A.: Personal communication to the authors.
110 +
Horner, F. A., and Streamer, C. W.: Personal communication to the authors.
111 +
Dalgliesh, C. E.:  Metabolism of the Aromatic Amino Acids , in Advances in Protein Chemistry , Vol. 10, New York, Academic Press, Inc., 1955;.
112 +
Armstrong, M. D., and Binkley, E. L., Jr.: Studies on Phenylketonuria: V. Observations on a Newborn Infant with Phenylketonuria, to be published.
113 +
Waelsch, H.:  Quantitative Aspects of the Metabolic Error in Oligophrenia Phenylpyruvica , in Biology of Mental Health and Disease , New York, Paul B. Hoeber, Inc., 1952;.
114 +
Kobayashi, T.; Saito, T.; Kanamura, K., and Koga, F.:  Ueber drei Geschwisterfälle der phenylpyruvischen Oligophrenie , Shonika Riusko , 5:6, 1952;.
115 +
Bhaskaran, K.:  Phenyl Pyruvic Oligophrenia: A Short Review with the Report of an Affected Family , Indian M. Gaz. 87:506, 1952;.
116 +
Cawte, J. E.:  Phenylketonuria , M. J. Australia 2:15-19, 1954;.

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References

1 +
Fölling, A.:  Ueber Ausscheidung von Phenylbrenztraubensäure in den Harn als Stoffwechselanomalie in Verbindung mit Imbezillität , Ztschr. Physiol. Chem. 227:169, 1935;.
2 +
Penrose, L. S.:  Two Cases of Phenylpyruvic Amentia , Lancet 1:23, 1935;.
3 +
Jervis, G. A.:  Phenylpyruvic Oligophrenia: Introductory Study of 50 Cases of Mental Deficiency Associated with Excretion of Phenylpyruvic Acid , Arch. Neurol. & Psychiat. 38:944, 1937;.
4 +
Brügger, C.:  Die Ausscheidung von Phenylbrenztraubensäure im Urin von Schwachsinnigen , Schweiz. Arch. Neurol. u. Psychiat. 49:62, 1942;.
5 +
Jervis, G. A.:  Phenylpyruvic Oligophrenia (Phenylketonuria) , A. Res. Nerv. & Ment. Dis., Proc. 33:259, 1954;.
6 +
Cowie, V.:  Phenylpyruvic Oligophrenia , J. Ment. Sc. 97:505, 1951;.
7 +
Penrose, L. S.:  Phenylketonuria: A Problem in Eugenics , Lancet 1:949, 1946;.
8 +
Penrose, L. S.: Biology of Mental Defect , New York, Grune & Stratton, Inc., 1949;.
9 +
Cowie, V. A.:  Atypical Case of Phenylketonuria , Lancet 1:272, 1951;.
10 +
Harris, H.: An Introduction to Human Biochemical Genetics, Eugenics Laboratory Memoirs , 37, London, Cambridge University Press, 1953;.
11 +
Bates, R. M.:  Three Cases of Phenylpyruvic Oligophrenia , J. Ment. Sc. 85:273, 1939;.
12 +
Mautner, H., and Quinn, K. V.:  Phenylpyruvic Oligophrenia , Ann. paediat. 172:1, 1949;.
13 +
Woolf, L. I., and Vulliamy, D. G.:  Phenylketonuria with a Study of Effect upon It of Glutamic Acid , Arch. Dis. Childhood 26:487, 1951;.
14 +
Cowie, V. A., and Penrose, L. S.:  Dilution of Hair Colour in Phenylketonuria , Ann. Eugenics 15:297, 1951;.
15 +
Levy, S., and Perry, H. A.:  Phenylpyruvic Acid Factor in Mental Deficiency and Mental Illness , Am. J. Ment. Deficiency 54:73, 1949;.
16 +
Frazier, R. L.:  Phenylpyruvic Amentia: Report of an Institution Survey , Am. J. Ment. Deficiency 51:577, 1947;.
17 +
Benda, C. E.: Developmental Disorders of Mentation and Cerebral Palsies , New York, Grune & Stratton, Inc., 1952;.
18 +
Josephy, H.:  Phenylpyruvic Oligophrenia (Report on 16 Clinical Cases and 2 Autopsies) , Illinois M. J. 94:107, 1948;.
19 +
Cantor, S. J.:  Phenylpyruvic Oligophrenia, with Notes on New Case and Report of Laboratory Investigations in an Earlier Case , M. J. Australia 1:69, 1952;.
20 +
Warthen, R. O.; Tandeta, M., and Williams, J. M.:  Phenylpyruvic Oligophrenia: 2 Cases of Siblings , Am. J. Dis. Child. 78:759, 1949;.
21 +
Meldicott, R. W.:  Phenylpyruvic Oligophrenia , New Zealand M. J. 43:101, 1944;.
22 +
Penrose, L. S.:  Measurement of Pleiotropic Effects on Phenylketonuria , Ann. Eugenics 16:134, 1951;.
23 +
Penrose, L. S.:  Inheritance of Phenylpyruvic Amentia (Phenylketonuria) , Lancet 2:192, 1935;.
24 +
Jervis, G. A.:  Genetics of Phenylpyruvic Oligophrenia , J. Ment. Sc. 85:719, 1939;.
25 +
Munro, T. A.:  Phenylketonuria: Data on 47 British Families , Ann. Eugenics 14:60, 1949;.
26 +
Larson, C. A.:  An Estimate of the Frequency of Phenylketonuria in South Sweden , Folia hered. et path. 4:40, 1954;.
27 +
Fölling, A., and Closs, K.:  Über das Vorkommen von 1-Phenylalanin in Harn und Blut bei Imbecillitas phenylpyrouvica , Ztschr. physiol. Chem. 254:115-116, 1938;.
28 +
Brügger, C.:  The Elimination of Phenylpyruvic Acid by Mentally Deficient Individuals , Schweiz. med. Wchnschr. 73:967, 1943;
29 +
J. Ment. Sc. 92:269, 1946;.
30 +
Fölling, A.; Mohr, O. L., and Ruud, L.: Oligophrenia Phenylpyrouvica: A Recessive Syndrome in Man , Oslo, Dybwad, 1945;.
31 +
Cohen, P., and Kozinn, P. J.:  Phenylpyruvic Oligophrenia in Jewish Child , J. Pediat. 34:76, 1949;.
32 +
Fernandes, J. F.:  Phenylpyruvic Oligophrenia in the Dark-Skinned Person , Brasil-m éd. 64:225, 1950;
33 +
J. Ment. Sc. 97:855, 1951;.
34 +
Penrose, L. S.:  A Search for Linkage Between the A. B. O. Agglutinogens and Phenylketonuria , Am. J. Ment. Deficiency 50:4, 1945;.
35 +
Patients in Mental Institutions, Part 1, Public Institutions for Mental Defectives and Epileptics , U. S. Public Health Service Publication, No. 483, (Part 1) , 1952;.
36 +
Lerner, A. B.:  Metabolism of Phenylalanine and Tyrosine , in Advances in Enzymology , Edited by F. F. Nord, Vol. 14, New York, Interscience Publishers, Inc., 1953;, p. 73.
37 +
Knox, W. E.:  The Metabolism of Phenylalanine and Tyrosine , in Amino Acid Metabolism , Edited by W. D. McElroy and B. Glass, Baltimore, Johns Hopkins Press, 1955;.
38 +
Jervis, G. A.:  Phenylpyruvic Oligophrenia Deficiency of Phenylalanine-Oxidizing System , Proc. Soc. Exper. Biol. & Med. 82:514, 1953;.
39 +
Woolf, L. I.:  Excretion of Conjugated Phenylacetic Acid in Phenylketonuria , Biochem. J. 49:ix, 1951;.
40 +
Stein, W. H., Paladini, A. C., Hirs, C. H. W., and Moore, S.:  Phenylacetylglutamine as a Constituent of Normal Human Urines , J. Am. Chem. Soc. 76:2848, 1954;.
41 +
Armstrong, M. D.; Shaw, K. N. F., and Robinson, K. S.:  Studies on Phenylketonuria: II. The Excretion of o-Hydroxyphenylacetic Acid in Phenylketonuria , J. Biol. Chem. 213:797, 1955;.
42 +
Armstrong, M. D., and Shaw, K. N. F.:  Studies on Phenylketonuria: III. The Metabolism of o-Tyrosine , J. Biol. Chem. 213:805, 1955;.
43 +
Boscott, R. J., and Bickel, H.:  Detection of Some New Abnormal Metabolites in the Urine of Phenylketonuria, Scandinav . J. Clin. & Lab. Invest. 5:380, 1953;.
44 +
Boscott, R. J., and Bickel, H.:  Phenylalanine and Tyrosine Metabolism in Patients with Phenylketonuria , Biochem. J. 56:1, 1954;.
45 +
Jervis, G. A.:  Studies on Phenylpyruvic Oligophrenia: Position of Metabolic Error , J. Biol. Chem. 169:651, 1947;.
46 +
Delay, J.; Pichot, P.; Delbarre, F., and Taseel, J.:  L'oligophrénie phénylpyruvique; nouvelles observations , Bull. et mém. Soc. méd. hôp. Paris 64:669, 1948;.
47 +
(Cited by Cowie, V. A.: J. Ment. Sc. 97:505, 1951;.
48 +
Cowie, V. A.:  Galactose Tolerance Test in Phenylketonuria , J. Ment. Sc. 96:799, 1950;.
49 +
Pichot, D.; Delay, J., and Bertagna, L.: L'oligophrénie phénylpyruvique, Extrait Annales Médico-Psychologiques, No. 3, 1949.
50 +
V. A.: J. Ment. Sc. 97:505, 1951;.
51 +
Udenfriend, S., and Bessman, S. P.:  Hydroxylation of Phenylalanine and Antipyrine in Phenylpyruvic Oligophrenia , J. Biol. Chem. 203: 961, 1953;.
52 +
Weil-Malherbe, H., in Biochemistry of the Developing Nervous System , Edited by Waelsch, H., New York, Academic Press, Inc., 1955;, p. 427.
53 +
Harley-Mason, J., and Cromartie, R. I. T.: Formation of Monohydroxyindoles from Dihydroxyphenalanine, Proceedings of the Biochemical Society, Biochem. J. 51:xxiv, 1952.
54 +
Armstrong, M. D., and Robinson, K. S.:  On the Excretion of Indole Derivatives in Phenylketonuria , Arch. Biochem. 52:287, 1954;.
55 +
Jepson, J. B.:  Paper Chromatography of Urinary Indoles , Lancet 2:1009, 1955;.
56 +
Ferrari, V.; Campagnari, F., and Guida, A.:  Phenylpyruvic Oligophrenia: New Chemico Pathological Findings , Minerva med. 46:119, 1955;;
57 +
Abstract, J. A. M. A. 159:1160, 1955;.
58 +
Dent, C. E.: Personal Communication cited in Year Book of Pediatrics , 1955;-56, Chicago, The Year Book Publishers, Inc., p. 59.
59 +
Jervis, G. A.; Block, R. J.; Bolling, D., and Kanze, E.:  Chemical and Metabolic Studies on Phenylalanine: Phenylalanine Content of the Blood and Spinal Fluid in Phenylpyruvic Oligophrenia , J. Biol. Chem. 134:105, 1940;.
60 +
Borek, E.; Brecher, A.; Jervis, G. A., and Waelsch, H.:  Oligophrenia Phenylpyruvica; Constancy of Metabolic Error , Proc. Soc. Exper. Biol. & Med. 75:86, 1950;.
61 +
Block, R. J.; Jervis, G. A.; Bolling, D., and Webb, M.:  Chemical and Metabolic Studies on Phenylalanine: Amino Acid Content of Tissue Proteins of Normal and Phenylpyruvic Oligophrenic Individuals: Note on the Estimation of Phenylalanine , J. Biol. Chem. 134:567, 1940;.
62 +
Schrappe, O.:  Zur pathologischen Physiologie des Phenylbrenztraubensäure-Schwachsinns , Nervenarzt 23:175, 1952;.
63 +
Penrose, L. S., and Quastel, J. H.:  Metabolic Studies on Phenylketonuria , Biochem. J. 31:266, 1937;.
64 +
Dann, M.; Marples, E., and Levine, S. Z.:  Phenylpyruvic Oligophrenia: Report of Case in Infant with Quantitative Chemical Studies of Urine . J. Clin. Invest. 22:87, 1943;.
65 +
Dobriner, K.; Rhoads, C. P., and Lieberman, S.:  Spectroscopy as Applied to the Study of Phenylpyruvic Oligophrenia: Role of Nutritional Deficiency in Nervous and Mental Disease , Res. Nerv. & Ment. Dis. Proc. 22:158, 1943;.
66 +
Jervis, G. A.:  Studies on Phenylpyruvic Oligophrenia: Phenylpyruvic Acid Content of Blood , Proc. Soc. Exper. Biol. & Med. 81:715, 1953;.
67 +
Jervis, G. A.:  Metabolic Investigations on Case of Phenylpyruvic Oligophrenia , J. Biol. Chem. 126:305, 1938;.
68 +
Jervis, G. A.:  Excretion of Phenylalanine and Derivatives in Phenylpyruvic Oligophrenia , Proc. Soc. Exper. Biol. & Med. 75:83, 1950;.
69 +
Lepow, H.:  Phenylpyruvic Oligophrenia: A Clinical and Biochemical Study , Monatsschr. Psychiat. u. Neurol. 110:161, 1945;
70 +
J. Ment. Sc. 92:649, 1946;.
71 +
Snyderman, S. E.; Norton, P., and Holt, L. E., Jr.:  Effect of Tyrosine Administration in Phenylketonuria , Fed. Proc. 14:450, 1955;.
72 +
Meister, A.; Udenfriend, S., and Bessman, S. P.:  Diminished Phenylketonuria in Phenylpyruvic Oligophrenia After Administration of L-Glutamine, L-Glutamate or L-Asparagine , J. Clin. Invest. 35:619, 1956;.
73 +
Albanese, A. A.:  Colorimetric Estimation of Phenylalanine in Some Biological Products , J. Biol. Chem. 155:291, 1944;.
74 +
Block, R. J., and Bolling, D.:  Chemical and Metabolic Studies on Phenylalanine: The Nitration of Phenylalanine , J. Biol. Chem. 129:1, 1939;.
75 +
Udenfriend, S., and Cooper, J. R.:  Assay of L-Phenylalanine as Phenylethylamine After Enzymatic Decarboxylation; Application to Isotope Study , J. Biol. Chem. 203:953, 1953;.
76 +
Prescott, B. A.; Borek, E.; Brecher, A., and Waelsch, H.:  Studies on Oligophrenia Phenylpyruvica; Microbiological Determination of L-and D-Phenylalanine and of Phenyllactic Acid , J. Biol. Chem. 181:273, 1949;.
77 +
Armstrong, M. D.: Personal communication to the authors.
78 +
Berry, J. P., and Woolf, L. I.:  Estimation of Phenylpyruvic Acid , Nature , London 169:202, 1952;.
79 +
Kondritzer, A. A.:  Precipitation Pattern of Serum Proteins in Phenylpyruvic Oligophrenia , Proc. Soc. Exper. Biol. & Med. 44:404, 1940;.
80 +
Brown, D. M.; Armstrong, M. D., and Smith, E. L.:  Studies on Phenylketonuria: Serum Proteins in Phenylketonuria , Proc. Soc. Exper. Biol. & Med. 89:367, 1955;.
81 +
Pauling, L.: Personal communication to the authors.
82 +
Pugh, C. E. M.:  The Use of Creatine-Creatinine Ratio , J. Ment. Sc. 86:240, 1940;.
83 +
Himwich, H. E., and Fazekas, J. F.:  Cerebral Metabolism in Mongolian Idiocy and Phenyl-Pyruvic Oligophrenia , Arch. Neurol. & Psychiat. 44:1213, 1940;.
84 +
Weil-Malherbe, H.:  Blood Adrenalin and Intelligence , in Biochemistry of the Developing Nervous System , Edited by Waelsch, H., New York, Academic Press, Inc., 1955;.
85 +
Kreezer, G. L.:  Research in Progress upon the Electroencephalogram in Mental Deficiency . Proc. Am. Ment. Deficiency 63:120, 1939;
86 +
Abstract, J. Ment. Deficiency 86:1123, 1940;.
87 +
Fois, A.; Rosenberg, C., and Gibbs, F. A.:  The Electroencephalogram in Phenylpyruvic Oligophrenia, Electroencephalog . & Clin. Neurophysiol. 7:569, 1955;.
88 +
Gibbs, F. A., and Gibbs, E. L.:  Phenylpyruvic Amentia , in Atlas of Electroencephalography , Reading, Mass., Addison-Wesley Publishing Company, Inc., 1950;.
89 +
Alvord, E. C., Jr.; Stevenson, L. D.; Vogel, F. S., and Engle, R. L., Jr.:  Neuropathological Findings in Phenyl-Pyruvic Oligophrenia (Phenylketonuria) , J. Neuropath. & Exper. Neurol. 9:298, 1950;.
90 +
Penrose, L. S.:  Peripheral Nerve Tumors in Case of Phenylketonuria , Lancet 1:572, 1939;.
91 +
Corsellis, J. A. N.:  Pathological Report of Case of Phenylpyruvic Oligophrenia , J. Neurol. Neurosurg. & Psychiat. 16:139, 1953;.
92 +
Bickel, H.; Gerrard, J., and Hickmans, E. M.:  Influence of Phenylalanine Intake on Chemistry and Behavior of a Phenylketonuric Child , Acta. paediat. 43:64, 1954;.
93 +
Bickel, H.; Boscott, R. J.; Gerrard, J., and Waelsch, H.:  Observations on the Biochemical Error in Phenylketonuria and Its Dietary Control , in Biochemistry of the Developing Nervous System , Edited by H. Waelsch, New York, Academic Press, Inc., 1955;.
94 +
Woolf, L. I.; Griffiths. R., and Moncrieff, A.:  Treatment of Phenylketonuria with a Diet Low in Phenylalanine , Brit. M. J. 2:57, 1955;.
95 +
Armstrong, M. D., and Tyler, F. H.:  Studies on Phenylketonuria: Restricted Phenylalanine Intake in Phenylketonuria , J. Clin. Invest. 34:565, 1955;.
96 +
Horner, F. A., and Streamer, C. W.:  Effect of a Phenylalanine-Restricted Diet on Patients with Phenylketonuria , J. A. M. A. 161:1628, 1956;.
97 +
Bosma, J. F.; Low, N. L.; Armstrong, M. D.; Tyler, F. H.; Madsen, J. A., and Carlisle, J. W.:  Clinical Effects of Phenylalanine Restrictive Diet in Phenylketonuria , Presented at Society for Pediatric Research, Buck Hill Falls, Pa. , 1956;.
98 +
Cares, R. M.:  Absence of Phenylketonuria in Adult Psychotics: A Survey of 4246 Inmates of a State Mental Hospital , Am. J. Psychiat. 112: 938, 1956;.
99 +
Dancis, J., and Balis, M. E.:  A Possible Mechanism for Disturbance in Tyrosine Metabolism in Phenylpyruvic Oligophrenia , Pediatrics 15:63, 1955;.
100 +
Hsia, D. V., and Driscoll, K.:  Detection of the Heterozygote in Phenylketonuria , Presented at the Society for Pediatric Research, Buck Hill Falls, Pa. , 1956;.
101 +
Lorcomb, J. W.:  Phenylketonuria and the Congenitally Deaf , J. Pediat. 14:348, 1939;.
102 +
Udenfriend, S.; Titus, E.; Weissbach, H., and Peterson, R. E.:  Biogenesis and Metabolism of 5-Hydroxyindole Compounds , J. Biol. Chem. 219:335, 1956;.
103 +
Brodie, B. B.; Pletscher, A. B., and Shore, P. A.:  Evidence that Serotonin Has a Role in Brain Function , Science 122:968, 1955;.
104 +
McGeer, P. L.; McGeer, E. G., and Gibson, W. C.:  Aromatic Excretory Pattern of Schizophrenics , Science 123:1029, 1956;.
105 +
McGeer, P. L.; McGeer, E. G., and Boulding, J. E.:  Relation of Aromatic Amino Acids to Excretory Pattern of Schizophrenics , Science 123:1078, 1956;.
106 +
Boscott, J. R., in Biochemistry of the Developing Nervous System , Edited by H. Waelsch, New York, Academic Press, Inc., 1955;, p. 428.
107 +
Larson, C. A.: The Absence of Phenylketonuria in 8220 Individuals not Known to be Mental Defectives, Novant'anni Delle Leggi Mendeliane , Rome, Instituto Gregorio Mendel, 1956;, p. 311.
108 +
Crowe, F. W., and Schull, W. J.:  Phenylketonuria: Studies in Pigment Formation , Folia hered. et path. 1:259, 1952;.
109 +
Jervis, G. A.: Personal communication to the authors.
110 +
Horner, F. A., and Streamer, C. W.: Personal communication to the authors.
111 +
Dalgliesh, C. E.:  Metabolism of the Aromatic Amino Acids , in Advances in Protein Chemistry , Vol. 10, New York, Academic Press, Inc., 1955;.
112 +
Armstrong, M. D., and Binkley, E. L., Jr.: Studies on Phenylketonuria: V. Observations on a Newborn Infant with Phenylketonuria, to be published.
113 +
Waelsch, H.:  Quantitative Aspects of the Metabolic Error in Oligophrenia Phenylpyruvica , in Biology of Mental Health and Disease , New York, Paul B. Hoeber, Inc., 1952;.
114 +
Kobayashi, T.; Saito, T.; Kanamura, K., and Koga, F.:  Ueber drei Geschwisterfälle der phenylpyruvischen Oligophrenie , Shonika Riusko , 5:6, 1952;.
115 +
Bhaskaran, K.:  Phenyl Pyruvic Oligophrenia: A Short Review with the Report of an Affected Family , Indian M. Gaz. 87:506, 1952;.
116 +
Cawte, J. E.:  Phenylketonuria , M. J. Australia 2:15-19, 1954;.

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