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Causes for High Phenylalanine With Normal Tyrosine:  In Newborn Screening Programs FREE

Julian L. Berman, MD; George C. Cunningham, MD; Robert W. Day, MD, PhD; Robin Ford, MA; David Y. Y. Hsia, MD
[+] Author Affiliations

Received for publication May 21, 1968.

Submitted by the authors for the Mary Efron Memorial Issue of the Journal.

The members of the Collaborative Study on Phenylketonuria dedicate this paper to the memory of Mary L. Efron, who was a faithful participant in all our deliberations from the beginning. We shall miss her, but will always treasure her friendship and remember her cheerful presence among us.

This paper represents a publication of the Collaborative Study on Phenylketonuria. In addition to the authors, the following participated in the study: Carl G. Ashley, MD, Portland, Ore; June Dobbs, MD, Milwaukee; James C. Dobson, PhD, Los Angeles; William Frankenburg, MD, Denver; Eleanor C. Gordon, MD, Philadelphia; David S. Klineman, MPH, Ann Arbor, Mich; Richard Koch, MD, Los Angeles; Margaret E. O'Flynn, MB, ChB, Chicago; Ira M. Rosenthal, MD, Chicago; Harry A. Waisman, MD, Madison, Wis; and Robert Warner, MD, Buffalo.

Presented at the American Pediatrics Society, Atlantic City, NJ, May 1, 1968.

Reprint requests to 1400 S First Ave, Hines, Ill 60141 (Dr. Hsia).


Am J Dis Child. 1969;117(1):54-65. doi:10.1001/archpedi.1969.02100030056006.
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ALTHOUGH phenylketonuria was described by Asbjörn Fölling1 over 30 years ago, it is only recently that we have begun to appreciate the full clinical spectrum of the disorder and to get a critical appraisal of the value of a low-phenylalanine diet in preventing the mental defect in such patients.2

Much of this confusion has come about because of differences in methods of ascertainment for phenylketonuria. In the beginning, it was felt that the disorder could only be detected in the patient who developed clinical symptoms, most prominently mental retardation. As a result, it was believed that all patients with phenylketonuria were mentally defective3 and the occasional "atypical" phenylketonuric person with normal or near-normal intelligence was considered to be sufficiently unusual as to be worthy of reporting separately.4 Since treatment was of little benefit once mental deficiency was already present, very few data were available on treatment

REFERENCES

Fölling, A.:  Über Ausscheidung von Phenyl[ill] brenztraubensaure in den Harn als Stoffweichsel[ill] anemalie in Verbindung mit Imbezillität , Z Physiol Chem 227:169-176, 1934;.
Hsia, D.Y.Y.:  Phenylketonuria 1967 , Develop Med Clin Neurol 9:531-540 ( (Oct) ) 1967;.
Penrose, L.S.:  Measurement of Pleiotropic Effects in Phenylketonuria , Ann Eugenics 16:134-141, 1951;.
Knox, W.E.:  An Evaluation of the Treatment of Phenylketonuria With Diets Low in Phenylalanine , Pediatrics 26:1-11 ( (July) ) 1960;.
Gibbs, N.K., and Woolf, L.I.:  Tests for Phenylketonuria in Results of a One-Year Programme for Its Detection in Infancy and Among Mental Defectives , Brit Med J 2:532-535, 1959;.
Guthrie, R., and Susi, A.:  A Simple Phenylalanine Method for Detecting Phenylketonuria in Large Populations of Newborn Infants , Pediatrics 32:338-343 ( (Sept) ) 1963;.
Hsia, D.Y.Y.; Berman, J.L.; and Slatis, H.M.:  Screening Newborn Infants for Phenylketonuria , JAMA 188:203-206 ( (April 20) ) 1964;.
Anderson, J.A., et al:  Atypical Phenylketonuric Heterozygote , J Pediat 68:351-360 ( (March) ) 1966;.
Auerbach, V.H.; DiGeorge, A.M.; and Carpenter, G.C.: " Phenylalanemia ," in W. L. Nyhan (ed.), Amino Acid Metabolism and Genetic Variation , New York: McGraw-Hill Book Co., 1968;, p 11.
Berlow, S., and Arends, R.L.:  Neonatal Phenylalaninemia in Heterozygotes for Phenylketonuria , J Pediat 68:835 ( (May) ) 1966;.
Schneider, A.J., and Garrard, S.D.:  Diagnostic and Therapeutic Implications of Persistent Hyperphenylalanemia in an Infant Heterozygous for the Gene of Phenylketonuria , J Pediat 68:704-712 ( (March) ) 1966;.
Justice, P.; O'Flynn, M.E.; and Hsia, D.Y.Y.:  Phenylalanine Hydroxylase Activity in Hyperphenylalanemia , Lancet 1:928-929 ( (April 20) ), 1967;.
O'Flynn, M.E.; Tillman, P.; and Hsia, D.Y.Y.:  Hyperphenylalanemia Without Phenylketonuria , Amer J Dis Child 113:22-30 ( (Jan) ) 1967;.
Ouellette, E.M., et al: The Clinical Problem of Atypical Phenylketonuria: Apparent Biochemical Remission in a Severely Retarded Patient, Amer J Dis Child, to be published.
Bessman, S.P.:  Legislation and Advances in Medical Knowledge , J Pediat 69:334-338 ( (Aug) ) 1966;.
Gerald, P.S.:  The Dangers of a Successful PKU Program , Pediatrics 39:325-326 ( (March) ) 1967;.
Berry, H.K., and Wright, S.:  Conferences on Treatment of Phenylketonuria , J Pediat 70:142-147 ( (Jan) ) 1967;.
McCaman, M.W., and Robbins, E.:  Fluorimetric Method for the Determination of Phenylalanine in Serum , J Lab Clin Med 59:885-890 ( (March) ) 1962;.
Rubinstein, J.M., and Taybi, M.:  Broad Thumbs and Toes and Facial Abnormalities , Amer J Dis Child 105:588-608 ( (March) ) 1963;.
Berman, J.L., et al: Phenylalanine Tolerance Tests in Families With Phenylketonuria and Hyperphenylalanemia, to be published.
Hsia, D.Y.Y.; O'Flynn, M.E.; and Berman, J.L.:  Atypical Phenylketonuria With Normal or Borderline Intelligence , Amer J Dis Child 116:143-157 ( (Aug) ) 1968;.

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References

Fölling, A.:  Über Ausscheidung von Phenyl[ill] brenztraubensaure in den Harn als Stoffweichsel[ill] anemalie in Verbindung mit Imbezillität , Z Physiol Chem 227:169-176, 1934;.
Hsia, D.Y.Y.:  Phenylketonuria 1967 , Develop Med Clin Neurol 9:531-540 ( (Oct) ) 1967;.
Penrose, L.S.:  Measurement of Pleiotropic Effects in Phenylketonuria , Ann Eugenics 16:134-141, 1951;.
Knox, W.E.:  An Evaluation of the Treatment of Phenylketonuria With Diets Low in Phenylalanine , Pediatrics 26:1-11 ( (July) ) 1960;.
Gibbs, N.K., and Woolf, L.I.:  Tests for Phenylketonuria in Results of a One-Year Programme for Its Detection in Infancy and Among Mental Defectives , Brit Med J 2:532-535, 1959;.
Guthrie, R., and Susi, A.:  A Simple Phenylalanine Method for Detecting Phenylketonuria in Large Populations of Newborn Infants , Pediatrics 32:338-343 ( (Sept) ) 1963;.
Hsia, D.Y.Y.; Berman, J.L.; and Slatis, H.M.:  Screening Newborn Infants for Phenylketonuria , JAMA 188:203-206 ( (April 20) ) 1964;.
Anderson, J.A., et al:  Atypical Phenylketonuric Heterozygote , J Pediat 68:351-360 ( (March) ) 1966;.
Auerbach, V.H.; DiGeorge, A.M.; and Carpenter, G.C.: " Phenylalanemia ," in W. L. Nyhan (ed.), Amino Acid Metabolism and Genetic Variation , New York: McGraw-Hill Book Co., 1968;, p 11.
Berlow, S., and Arends, R.L.:  Neonatal Phenylalaninemia in Heterozygotes for Phenylketonuria , J Pediat 68:835 ( (May) ) 1966;.
Schneider, A.J., and Garrard, S.D.:  Diagnostic and Therapeutic Implications of Persistent Hyperphenylalanemia in an Infant Heterozygous for the Gene of Phenylketonuria , J Pediat 68:704-712 ( (March) ) 1966;.
Justice, P.; O'Flynn, M.E.; and Hsia, D.Y.Y.:  Phenylalanine Hydroxylase Activity in Hyperphenylalanemia , Lancet 1:928-929 ( (April 20) ), 1967;.
O'Flynn, M.E.; Tillman, P.; and Hsia, D.Y.Y.:  Hyperphenylalanemia Without Phenylketonuria , Amer J Dis Child 113:22-30 ( (Jan) ) 1967;.
Ouellette, E.M., et al: The Clinical Problem of Atypical Phenylketonuria: Apparent Biochemical Remission in a Severely Retarded Patient, Amer J Dis Child, to be published.
Bessman, S.P.:  Legislation and Advances in Medical Knowledge , J Pediat 69:334-338 ( (Aug) ) 1966;.
Gerald, P.S.:  The Dangers of a Successful PKU Program , Pediatrics 39:325-326 ( (March) ) 1967;.
Berry, H.K., and Wright, S.:  Conferences on Treatment of Phenylketonuria , J Pediat 70:142-147 ( (Jan) ) 1967;.
McCaman, M.W., and Robbins, E.:  Fluorimetric Method for the Determination of Phenylalanine in Serum , J Lab Clin Med 59:885-890 ( (March) ) 1962;.
Rubinstein, J.M., and Taybi, M.:  Broad Thumbs and Toes and Facial Abnormalities , Amer J Dis Child 105:588-608 ( (March) ) 1963;.
Berman, J.L., et al: Phenylalanine Tolerance Tests in Families With Phenylketonuria and Hyperphenylalanemia, to be published.
Hsia, D.Y.Y.; O'Flynn, M.E.; and Berman, J.L.:  Atypical Phenylketonuria With Normal or Borderline Intelligence , Amer J Dis Child 116:143-157 ( (Aug) ) 1968;.

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