The hyperphenylalaninemias of man and mouse

Annual Review of Genetics

Volumn 28, Issue , 1994, Pages 141-165

  Scriver, Charles R ^a   Eisensmith, Randy C ^b   Woo, Savio L C ^b   Kaufman, Seymour ^c  

^a RESEARCH INSTITUTE OF THE MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^b BAYLOR COLLEGE OF MEDICINE   (United States)

^c NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

PAH gene: human; Pah gene: mouse; phenylalanine hydroxylase; phenylalanine hydroxylation reaction; phenylketonuria; tetrahydrobiopterin synthesis and recycling

Indexed keywords

PHENYLALANINE 4 MONOOXYGENASE;

GENOTYPE; HAPLOTYPE; HUMAN; HYPERPHENYLALANINEMIA; MOUSE; MUTANT; NONHUMAN; PHENOTYPE; POPULATION GENETICS; PRIORITY JOURNAL; REVIEW;

EID: 0028596297     PISSN: 00664197     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.genet.28.1.141     Document Type: Review

References (158)

1. Alder C, Ghisla S, Rebrin I, Heizmann CW, Blau N, et al. 1992. Suspected pterin-4a-carbinolamine dehydratase deficiency: Hyperphenylalaninemia due to inhibition of phenylalanine hydroxylase by tetrahydro-7-biopterin. J. Inherit. Metab. Dis. 15:405-8
2. Al Aqueel A, Ozand PT, Gascon GG, Hughes H, Reynolds CT, et al. 1992. Response of 6-pyruvoyl-tetrahydropterin synthase deficiency to tetrahydrobiopterin. J. Child Neurol. 7: S26-30 (Suppl.)
3. Anon. 1993. Phenylketonuria due to phenylalanine hydroxylase deficiency: an unfolding story. Br. Med. J. 306:115-19
4. Anon. 1993. Recommendations on the dietary management of phenylketonuria. Rep. Med. Res. Counc. Work. Party Phenylketonuria. Arch. Dis. Child. 68: 426-27
5. Apold J, Eiken HG, Froysa KE, Moyzfeldt K. 1993. Estimation of the severity of individual hyperphenylalaninemia mutations from untreated serum phenylalanine concentration. Dev. Brain Dysfunct. 6:109-13
6. Armarego WLF, Cotton RGH, Dahl HHM, Dixon NE. 1989. High-level expression of human dihydropteridine reductase (EC 1.6.99.7), without N-terminal amino acid protection in Escherichia coli. Biochem. J. 261:256-58
7. Avigad S, Cohen BE, Bauer S, Schwartz G, Frydman M, et al. 1990. A single origin of phenylketonuria in Yemenite Jews. Nature 334:168-70
8. Bearn AG. 1993. Archibald Garrod and the Individuality of Man. Oxford: Clarendon
9. Beaudet AL, Tsui L-C. 1993. A suggested nomenclature for designating mutations. Hum. Mutat. 2:245-48
10. Bick U, Fahrendorf G, Ludoph AC, Vassallo P, Weglage J, et al. 1991. Disturbed myelination in patients with treated hyperphenylalaninemia: Evaluation with magnetic resonance imaging. Eur. J. Pediatr. 150:185-89
11. 10a. Blau N, Curtius H-Ch, Levine R, Yim J, eds. 1992. Pteridines and Related Biogenic Amines and Folates. Seoul: Hanrim Publ.
12. Blau N, Heizmann CW, Sperl W, Korenke GC, Hoffman GF, et al. 1992. Atypical (mild) forms of dihydropteridine reductase deficiency: Neurochemical evaluation and mutation detection. Pediatr. Res. 32:726-30
13. Blau N, Thöny B, Heizmann CW, Dhondt J-L. 1993. Tetrahydrobiopterin deficiency: From phenotype to genotype. Pteridines 4:1-10
14. Bode V, McDonald J, Guenet J, Simon D. 1988. hph-1: A mouse mutant with hereditary hyperphenylalaninemia induced by ethylnikrosourea mutagenesis. Genetics 118:299-305
15. Bodley JL, Austin VJ, Hanley WB, Clarke JTR, Zlotkin S. 1993. Low iron stores in infants and children with treated phenylketonuria: a population at risk for iron-deficiency anaemia and associated cognitive deficits. Eur. J. Pediatr. 152:140-43
16. Burgisser D, Leimbacher W, Redweik CW, Thöny B. 1993. Malignant hyperphenylalaninemia caused by mutations in a human biosynthetic gene for tetrahydropterin. Experientia 19:14 (Abstr.)
17. Burgisser DM, Thöny B, Redweik U, Hunziker P, Heizmann CW, et al. 1994. Expression and characterization of recombinant human and rat liver 6-pyruvoyl tetrahydropterin synthase-modified cysteine residues inhibit the enzymatic activity. Eur. J. Biochem. In press
18. Cartier L, Clow CL, Lippman-Hand A, Morissette J, Scriver CR. 1982. Prevention of mental retardation in offspring of hyperphenylalaninemic mothers. Am. J. Public Health 72:1386-90
19. Chakraborty R, Lidsky AS, Daiger SP, Guttler F, Sullivan S, et al. 1987. Polymorphic DNA haplotypes at the human phenylalanine hydroxylase locus and their relationship with phenylketonuria. Hum. Genet. 76:40-46
20. Citron BA, Davis MD, Kaufman S. 1992. Purification and biochemical characterization of recombinant rat liver phenylalanine hydroxylase produced in Escherichia coli. Protein Expr. Purif. 3:93-100
21. Citron BA, Davis MD, Milstien S, Gutierrez J, Mendel DB, et al. 1992. Identity of 4α-carbinolamine dehydratase, a component of the phenylalanine hydroxylation system, and DCoH, a transregulator of homeodomain proteins. Proc. Natl. Acad. Sci. USA 89:11891-94
22. Citron BA, Kaufman S, Milstien S, Naylor EW, Greene CL, et al. 1993. Mutation in the 4α-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism. Am. J. Hum. Genet. 53:768-74
23. Cotton RGH. 1993. Current methods of mutation detection. Mulat. Res. 285: 125-44
24. Cristiano RJ, Smith LC, Woo SLC. 1993. Hepatic gene therapy: adenovirus enhancement of receptor-mediated gene delivery and expression in primary hepatocytes. Proc. Natl. Acad. Sci. USA 90:2122-26
25. Curtius H-Ch, Adler C, Rebrin I, Heizmann C, Ghisla S. 1990. 7-substituted pterins: Formation during phenylalanine hydroxylation in the absence of dehydratase. Biochem. Biophys. Res. Commun. 172:1060
26. Dahl H-HM, Hutchison W, McAdam W, Wake S, Morgan FJ, et al. 1987. Human dihydropteridine reductase: characterization of a cDNA clone and its use in analysis of patients with dihydropteridine reductase deficiency. Nucleic Acids Res. 15:1921-32
27. Davis MD, Kaufman S. 1991. 7-Tetrahydrobiopterin is an uncoupled cofactor for rat hepatic phenylalanine hydroxylase. FEBS Lett. 285:17-20
28. Davis MD, Kaufman S, Milstien S. 1991. Conversion of 6-substituted tetrahydropterins to 7-isomers via phenylalanine hydroxylase-generated intermediates. Proc. Natl. Acad. Sci. USA 88:385
29. Davis MD, Kaufman S, Milstien S. 1992. Distribution of 4a-hydroxy-tetrahydropterin dehydratase in rat tissues. FEBS Lett. 1:73-76
30. Davis MD, Ribeiro P, Tipper J, Kaufman S. 1992. 7-tetrahydrobiopterin, a naturally occurring analogue of tetrahydrobiopterin, is a cofactor for and a potential inhibitor of the aromatic amino acid hydroxylases. Proc. Natl. Acad. Sci. USA 89:10109-13
31. Dhondt J-L. 1991. Strategy for the screening of tetrahydrobiopterin deficiency among hyperphenylalaninemic patients: 15-years experience. J. Inherit. Metab. Dis. 14:117-27
32. Dhondt J-L. 1993. Tetrahydrobiopterin deficiencies: Lessons from the compilation of 200 patients. Dev. Brain Dysfunct. 6:141-57
33. Dhondt J-L, Farriaux JP, Boudha A, Largilliere C, Ringel J, et al. 1985. Neonatal hyperphenylalaninemia presumably caused by guanosine triphosphate-cyclohydrolase deficiency. J. Pediatr. 106:954
34. Dianzani I, Howells DW, Ponzone A, Saleeba JA, Smooker PM, et al. 1993. Two new mutations in the dihydropteridine reductase gene in patients with tetrahydrobiopterin deficiency. J. Med. Genet. 30:465-69
35. Døskeland AP, Vintermyr OK, Flatmark T, Cotton RGH, Døskeland SO. 1992. Phenylalanine positively modules the cAMP-dependent phosphorylation and negatively modulates the vasopressininduced and okadaic-acid-induced phosphorylation of phenylalanine 4-monooxygenase in intact rat hepatocytes. Eur. J. Biochem. 206:161-70
36. Dworniczak B, Kalaydjieva L, Pankoke S, Aulehla-Scholz C, Allen G, et al. 1992. Analysis of exon 7 of the human phenylalanine hydroxylase gene: A mutation hot spot? Hum. Mutat. 1:138-49
37. Eisensmith RC, Okano Y, Dasovich M, Wang T, Güttler F, et al. 1992. Multiple origins for phenylketonuria in Europe. Am. J. Hum. Genet. 51:1355-65
38. Eisensmith RC, Woo SLC. 1992. Molecular basis of phenylketonuria and related hyperphenylalaninemias: Mutations and polymorphisms in the human phenylalanine hydroxylase gene. Hum. Mutat. 1:13-23
39. Eisensmith RC, Woo SLC. 1992. Letters to the Editor. Updated listing of haplotypes at the human phenylalanine hydroxylase (PAH) locus. Am. J. Hum. Genet. 51:1445-48
40. Feingold J, Guilloud-Bataille M, Feingold N, Rey F, Berthelon M, et al. 1993. Linkage disequilibrium in the human phenylalanine hydroxylase. Dev. Brain Dvsfunct. 6:26-31
41. Fisch RO, Tagatz G, Stassart JP. 1993. Gestational carrier - A reproductive haven for offspring of mothers with phenylketonuria (PKU): An alternative therapy for maternal PKU. J. Inherit. Metab. Dis. 16:957-61
42. Følling A. 1934. Uber Ausscheidung von Phenylbrenztraubensaure in den Harn als Stoffwechselanomalie in Verbindung mit Imbezillitat. Z. Physiol. Chem. 277:169
43. Goltsov AA, Eisensmith RC, Konecki DS, Lichter-Konecki U, Woo SLC. 1992. Associations between mutations and a VNTR in the human phenylalanine hydroxylase gene. Am. J. Hum. Genet. 51:627-36
44. Goltsov AA, Eisensmith RC, Naughton ER, Jin L, Chakraborty R, et al. 1993. A single polymorphic STR system in the human phenylalanine hydroxylase gene permits rapid prenatal diagnosis and carrier screening for phenylketonuria. Hum. Mol. Genet. 2:577-81
45. Grompe M. 1993. The rapid detection of unknown mutations in nucleic acids. Nat. Genet. 5:111-17
46. Gropper SS, Naglak MC, Nardella M, Plyler A, Rarback S, et al. 1993. Nutrient intakes of adolescents with phenylketonuria and infants and children with Maple Syrup Urine Disease on semisynthetic diets. J. Am. Coll. Nutr. 12:108-14
47. Guldberg P, Henriksen KF, Güttler F. 1993. Molecular analysis of phenylketonuria in Denmark: 99% of the mutations detected by denaturing gradient gel electrophoresis. Genomics 17:141-46
48. Guldberg P, Romano V, Ceratto N, Bosco P, China M, et al. 1993. Mutational spectrum of phenylalanine hydroxylase deficiency in Sicily - Implications for diagnosis of hyperphenylalaninemia in Southern Europe. Hum. Mol. Genet. 2:1703-7
49. Guttler F, Guldberg P, Henriksen KF, Mikkelsen I, Olsen B, et al. 1993, Molecular basis for the phenotypical diversity of phenylketonuria and related hyperphenylalaninaemias. J. Inherit. Metab. Dis. 16:602-4
50. Hajek B, Hejcmanova L, Pradny J. 1993. Proton in vivo spectroscopy of patients with hyperphenylalaninaemia. Neuropediatrics 24:111-12
51. Hanson KR, Havir EA. 1972. The enzymic elimination of ammonia. In The Enzymes, ed. PD Boyer, p. 75. New York: Academic
52. Hatakeyama K, Ashida A, Owada M, Kitagawa T, Mino M, Kagamiyama H. 1992. Molecular basis of malignant hyperphenylalaninemia: a mutation in the gene encoding human 6-pyruvoyltetrahydropterin synthase. See Ref. 10a, pp. 142-43
53. Hatakeyama K, Harada T, Kagamiyama H. 1992. Expression, purification and characterization of premature and mature forms of rat GTP cyclohydrolase I in Escherichia coli using mMal vector. See Ref. 10a, pp. 107-8
54. Hauer CR, Rebrin I.Thöny B, Neuheiser F, Curtius H-Ch, et al. 1993. Phenylalanine hydroxylase-stimulating protein/ pterin-4α-carbinolamine dehydratase from rat and human liver. J. Biol. Chem. 268:4828-31
55. 143 as the site of modification in the active site of histidine ammonia-lyase. Arch. Biochem. Biophys. 307:126-32
56. Hommes FA. 1993. The effect of hyperphenylalaninaemia on the muscarinic acetylcholine receptor in the HPH-5 mouse brain. J. Inherit. Metab. Dis. 16: 962-74
57. Hommes FA, Moss L. 1992. Myelin turnover in hyperphenylalaninemia. A re-evaluation with little HPH-5 mouse. J. Inherit. Metab. Dis. 15:243-51
58. Howells DW, Forrest SM, Dahl H-HM, Cotton RGH. 1990. Insertion of an extra codon for threonine is a cause of dihydropteridine reductase deficiency. Am. J. Hum. Genet. 47:279-85
59. Huang R-T, Lin S-J, Kuo P-L, Peng C-J. 1993. Successful managment of a pregnancy with maternal phenylketonuria: Report of a case. J. Formosan Med. Assoc. 92:182-84
60. Hyland K. 1993. Abnormalities of biogenie amine metabolism. J. Inherit. Metab. Dis. 16:676-90
61. Inoue Y, Kawasaki Y, Harada T, Hatakeyama K, Kagamiyama H. 1991. Purification and cDNA cloning of rat 6-pyruvoyl-tetrahydropterin synthase. J. RM. Chem. 266:20791-96
62. Jennings IG, Kemp BE, Cotton RGH. 1991. Localization of cofactor binding sites with monoclonal anti-idiotype antibodies: phenlylanine hydroxylase. Proc. Natl. Acad. Sci. USA 88:5734-38
63. John SWM, Rozen R, Scriver CR, Laframboise R, Laberge C. 1990. Recurrent mutation, gene conversion, or recombination at the human phenylalanine hydroxylase locus: Evidence in French-Canadians and a catalog of mutations. Am. J. Hum. Genet. 46:970-74
64. Kacser H, Burns JA. 1981. The molecular basis of dominance. Genetics 97: 639-66
65. Katzenmeier G, Schmid C, Bacher A. 1990. Cloning and expression of the putative gene coding for GTP cyclohydrolase I from Escherichia coli. FEMS Microbiol. Lett. 66:231-34
66. Katzenmeier G, Schmid C, Kellermann J, Lottspeich F, Bacher A. 1990. Sequence of GTP cyclohydrolase I from Escherichia coli. Biol. Chem. HoppeSeyler 66:231-34
67. Kaufman S. 1975. Studies on the mechanism of phenylalanine hydroxylase: Detection of an intermediate. In Chemistry and Biology of Pteridines, ed. W Pfleiderer, pp. 291-304. New York: Walter de Gruyter
68. Kaufman S. 1976. Phenylketonuria: Biochemical mechanisms. Adv. Neurochem. 2:1-132
69. Kaufman S. 1993. New tetrahydrobiopterin-dependent systems. Annu. Rev. Nutr. 13:261-86
70. Kaufman S. 1994. The phenylalanine hydroxylating system. Adv. Enzymol. Relat. Areas Mol. Biol. 67:77-264
71. Kecskemethy HH, Lobregt D, Levy HL. 1993. The use of gelatin capsules for ingestion of formula in dietary treatment of maternal phenylketonuria. J. Inherit. Metab. Dis. 16:111-18
72. Kidd KK. 1987. Phenylketonuria. Population genetics of a disease. Nature 327:282-83
73. Konecki DS, Lichter-Konecki U. 1991. The phenylalanine locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations. Hum. Genet. 87:377-88
74. Konecki DS, Wang Y, Trefz FK, Lichter-Konecki U, Woo SLC. 1992. Structural characterization of the 5′ regions of the human phenylalanine hydroxylase gene. Biochemistry 31:8363-68
75. Kornguth S, Gilbert-Barness E, Langer E, Hegstrand L. 1992. Golgi-Hopsch Silver study of the brain of a patient with untreated phenylketonuria, seizures, and cortical blindness. Am. J. Med. Genet. 44:443-48
76. Krause W, Epstein C, Averbrook A, Dembure P, Elsas L. 1986. Phenylalanine alters the mean power frequency of electroencephalograms and plasma L-DOPA in treated patients with phenylketonuria. Pediatr. Res. 20:1112-16
77. Krause W, Halminski M, McDonald L, Demure P, Salvo R, et al. 1985. Biochemical and neuropsychological effects of elevated plasma phenylalanine in patients with treated phenylketonuria. J. Clin. Invest. 75:40-48
78. Kunert E, Wolf C, Güttler F, Tyfield LA, Rutland P, et al. 1993. Correlation of phenotype and genotype in phenylketonuria patients of eastern FGR homozygous for the R408W and R261Q point mutations of the phenylalanine hydroxylase locus. Dev. Brain Dysfunct. 6:114-19
79. Kwon NS, Nathan CF, Stuehr DJ. 1989. Reduced biopterin as a cofactor in the generation of nitrogen oxides by murine macrophages. J. Biol. Chem. 264: 20496-501
80. Langenbeck U, Behbehani A, Mench-Hoinowski A. 1992. A synopsis of the unconjugated acidic transamination metabolites of phenylalanine in phenylketonuria. J. Inherit. Metab. Dis. 15: 136-44
81. Langenbeck U, Lukas HD, Mench-Hoinowski A, Stenzig KP, Lane JD. 1988. Correlative study of mental and biochemical phenotypes in never treated patients with classic phenylketonuria. Brain Dysfunct. 1:103-10
82. Lazarus RA, Benkovic SJ, Kaufman S. 1983. Phenylalanine hydroxylase stimulator protein is a 4a-carbinolamine dehydratase. J. Biol. Chem. 258:10960-62
83. Ledley FD, Grenett H, McGinnis-Shelnutt M, Woo SLC. 1986. Retroviral-mediated gene transfer of human phenylalanine hydroxylase into NIH 3T3 and hepatoma cells. Proc. Natl. Acad. Sci. USA 83:409-13
84. Ledley FD, Ledbetter SA, Ledbetter DH, Woo SLC. 1988. Localization of mouse phenylalanine hydroxylase locus on chromosome 10. Cytogenet. Cell Genet. 47:125-26
85. Legido A, Tonyes L, Carter D, Schoemaker A, DiGeorge A, et al. 1993. Treatment variables and intellectual outcome in children with classic phenylketonuria. Clin. Pediatr. 32:417-25
86. Lenke RR, Levy HL. 1980. Maternal phenylketonuria and hyperphenylala-ninemia. An international survey of untreated and treated pregnancies. New Engl. J. Med. 303:1202-8
87. Levy HL, Lobbregt D, Sansaricq C, Snyderman SE. 1992. Comparison of phenylketonuric and nonphenylketonuric sibs from untreated pregnancies in a mother with phenylketonuria. Am. J. Med. Genet. 44:439-42
88. Levy HL, Taylor RG, McInnes, RR. 1994. Disorders of histidine metabolism. See Ref. 120a
89. Lidsky A, Ledley HD, DiLella AG, Kwok SCM, Daiger SP, et al. 1985. Extensive restriction site polymorphism at the human phenylalanine hydroxylase locus and application in prenatal diagnosis of phenylketonuria. Am. J. Hum. Genet. 37:619-34
90. Liu T-J, Kay MA, Darlington GJ, Woo SLC. 1992. Reconstitution of enzymatic activity in hepatocytes of phenylalanine hydroxylase-deficient mice. Som. Cell Mol. Genet. 18:89-96
91. Lou HC, Toft PB, Andresen J, Mikkelsen I, Olsen B, et al. 1992. An occipito-temporal syndrome in adolescents with optimally controlled hyperphenylalaninemia. J. Inherit. Metab. Dis. 15:687-95
92. Ludolph AC, Ullrich K, Nedjat S, Masur H, Bick U. 1992. Neurological outcome in 22 treated adolescents with hyperphenylalaninemia. Acta Neurol. Scand. 85:243-48
93. Lyonnet S, Melle D, DeBraekeleer M, Laframboise R, Rey F, et al. 1992. Time and space clusters of the French-Canadian M1V phenylketonuria mutation in France. Am. J. Hum. Genet. 51:191-96
94. MacCready RA. 1974. Admissions of phenylketonuric patients to residential institutions before and after screening programs of the newborn infant. J. Pediatr. 85:383-85
95. Matsubara Y, Ikeda H, Endo H, Narisawa K. 1992. Dried blood spot on filter paper as a source of mRNA. Nucleic Acids Res. 20:1998
96. McDonald JD, Bode VC. 1988. Hyperphenylalaninemia in the hyp-1 mouse mutant. Pediatr. Res. 23:63-67
97. hph-55: a mouse mutant deficient in phenylalanine hydroxylase. Proc. Natl. Acad. Sci. USA 87:1965-67
98. McDonald JD, Bode VC, Dove WF, Shedlovsky A. 1990. The use of N-ethylN-nitrourea to produce mouse models for human phenylketonuria and hyperphenylalaninemia. Prog. Clin. Biol. Res. 340C:407-13
99. McDonald JD, Cotton R, Jennings I, Ledley F, Woo S, et al. 1988. Biochemical defect of the hph-1 mouse mutant is a deficiency of GTP-cyclohydrolase activity. J. Neurochem. 50:655-57
100. Mendel DB, Khavari PA, Conley PB, Graves MK, Hansen LP, et al. 1991. Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein. Science 254: 1762-67
101. Mikami H, Matsubara Y, Hayasaka K, Narisawa K, Obinata M, et al. 1990. Molecular analysis of dihydropteridine reductase deficiency and restoration of the enzyme activity by gene transfer. J. Inherit. Metab. Dis. 13:787-91
102. Milstien S, Kaufman S, Sakai N. 1993. Tetrahydrobiopterin biosynthesis defects examined in cytokine-stimulated fibroblasts. J. Inherit. Metab. Dis. 16: 975-81
103. Mollica F, Meli C, Lentini L, Di Raimondo S, Lisi R. 1993. Dietetic tolerance in the differential diagnosis of hyperphenylalaninemias due to phenylalanine hydroxylase deficiency. Dev. Brain Dysfunct. 6:172-78
104. Moncada S, Higgs A. 1993. The L-arginine-nitric oxide pathway. New Engl. J. Med. 329:2002-12
105. Nayman R, Thomson E, Scriver CR, Clow CL. 1979. Observations on the composition of milk-substitute products for treatment of inborn errors of amino acid metabolism. Comparisons with human milk. Am. J. Clin. Nutr. 32:1279-89
106. Niederwieser A, Blau N, Wang M, Joller P, Atares M, et al. 1984. GTP cyclohydrolase I deficiency, a new enzyme defect causing hyperphenylalaninemia with neopterin, biopterin, dopamine, and serotonin deficiencies and muscular hypotonia. Eur. J. Pediatr. 141:208-14
107. O'FlynnME. 1992. Newborn screening for phenylketonuria: Thirty years of progress. Curr. Probl. Pediatr. 4:159-65
108. Okano Y, Eisensmith RC, Güttler F, Lichter-Konecki U, Konecki DS, et al. 1991. Molecular basis of phenotypic heterogeneity in phenylketonuria. N. Engl. J. Med. 324:1232-38
109. Okano Y, Wang T, Eisensmith RC, Guttler F, Woo SLC. 1990. Recurrent mutation in the human phenylalanine hydroxylase. Am. J. Hum. Genet. 46: 919-24
110. Pavone L, Meli C, Nigro F, Lisi R, Di Raimondo S, et al. 1993. Late diagnosed phenylketonuria patients: Clinical pre-sentation and results of treatment. Dev. Brain Dysfunct. 6:184-87
111. Peng H, Armentano D, MacKenzie-Graham L, Shen R-F, Darlington G, et al. 1988. Retroviral-mediated gene transfer and expression of human phenylalanine hydroxylase in primary mouse hepatocytes. Proc. Natl. Acad. Sci. USA 85: 8146-50
112. Penrose LS. 1935. Inheritance of phenylpyruvic amentia (Phenylketonuria). Lancet 2:192-94
113. Penrose LS. 1946. Phenylketonuria. A problem in eugenics. Lancet 1: 949-53
114. Penrose LS, Quastel JH. 1937. Metabolic studies in phenylketonuria. Biochem. J. 31:266-71
115. Perez B, Desviat LR, Die M, Cornejo V, Chamoles NA, et al. 1993. Presence of the Mediterranean PKU mutation IVS10 in Latin America. Hum. Mol. Genet. 2:1289-90
116. Pietz J, Schmidt E, Matthis P, Kobialka B, de Sonneville L. 1993. EEGs in phenylketonuria I: Follow-up to adulthood; II: Short-term diet-related changes in EEGs and cognitive function. Dev. Med. Child Neurol. 35:54-64
117. Ponzone A, Dianzani I, Spada M, de Sanctis L., Guardamagna O, et al. 1993. Prenatal diagnosis in primary hyperphenylalaninemias. Dev. Brain Dysfunct. 6:158-67
118. Ramus SJ, Forrest SM, Pitt DB, Saleeba JA, Cotton RGH. 1993. Comparison of genotype and intellectual phenotype in untreated PKU patients. J. Med. Genet. 30:401-5
119. Schmid C, Ladenstein R, Luecke H, Huber R, Bacher A. 1992. Crystallization and preliminary crystallographic characterization of GTP cyclohydrolase I from Escherichia coli. J. Mol. Biol. 226:1279-81
120. Schuman EM, Madison DV. 1991. A requirement for the intercellular messenger nitric oxide in long-term potentiation. Science 254:1503-6
121. Scriver CR. 1967. Treatment in medical genetics. In Proc. Int. Congr. Hum. Genet., 3rd. ed. JF Crow, JV Neel, pp. 45-56. Baltimore: Johns Hopkins Univ. Press
122. 120a. Scriver CR, Beaudet AL, Sly WS, Valle D, eds. 1994. The Metabolic and Molecular Buses of Inherited Disease. New York: McGraw-Hill. In press
123. Scriver CR, Clow CL. 1980. Epitome of human biochemical genetics. Part I. New Engl. J. Med. 303:1336-42
124. Scriver CR, Clow CL. 1980. Phenylketonuria: Epitome of human biochemical genetics. Part II. New Engl. J. Med. 303:1394-400
125. Scriver CR, Clow CL. 1980. Phenylketonuria and other phenylalanine hydroxylation mutants in man. Annu. Rev. Genet. 14:179-202
126. Scriver CR, Clow CL. 1988. Avoiding phenylketonuria: Why parents seek prenatal diagnosis. J. Pediatr. 113: 495-97
127. Scriver CR, Clow CL, Kaplan P, Niederwieser A. 1987. Hyperphenylalaninemia due to deficiency of 6-pyruvoyl tetrahydropterin synthase. Unusual gene dosage effect in heterozygotes. Hum. Genet. 77:168-71
128. Scriver CR, Hoang L, Byck S, Prevost L. 1993. PAH Gene Mutat. Anal. Consort. Newsl.
129. Scriver CR, John SMW, Rozen R, Eisensmith R, Woo SLC. 1993. Associations between populations, phenylketonuria mutations and RFLP haplotypes at the phenylalanine hydroxylase locus: An overview. Dev. Brain Dysfunct. 6: 11-25
130. Scriver CR, Kaufman S, Eisensmith E, Woo SLC. 1994. The hyperphenylalaninemias. See Ref. 120a
131. Shedlovsky A, McDonald JD, Smyula D, Dove WF. 1993. Mouse models of human phenylketonuria. Genetics 134: 1205-10
132. Smith I. 1991. Disorders of tetrahydrobiopterin metabolism. In Inborn Metabolism Diseases. Diagnosis and Treatment, ed. J Fernandes, J-M Saudubray, K Tada, pp. 183-97. Berlin: Springer-Verlag
133. Smooker PM, Howells DW, Cotton RGH. 1993. Identification and in vitro expression of mutations causing dihydropteridine reductase deficiency. Biochemistry 32:6443-49
134. Svensson E, von Döbeln U, Eisensmith RC, Hagenfeldt L, Woo SLC. 1993. Relation between genotype and phenotype in Swedish phenylketonuria and hyperphenylalaninemia patients. Eur. J. Pediatr. 152:132-39
135. Svensson E, Wang Y, Eisensmith RC, Hagenfeldt L, Woo SLC. 1993. Three polymorphisms but no disease-causing mutations in the proximal part of the promotor of the phenylalanine hydroxylase gene. Eur. J. Hum. Genet. 1:306-13
136. Tanaka K, Kaufman S, Milstien S. 1989. Tetrahydrobiopterin, the cofactor for aromatic amino acid hydroxylases, is synthesized by a regulated proliferation of erythroid cells. Proc. Natl. Acad. Sci. USA 86:5864-67
137. Tayeh MA, Marietta MA. 1989. Macrophage oxidation of L-arginine to nitric oxide, nitrite, and nitrate. Tetrahydrobiopterin is required as a cofactor. J. Biol. Chem. 264:19654-58
138. Taylor RG, Garcia-Heras J, Sadler SJ, Lafreniere RG, Willard HF, et al. 1991. Localization of histidase to human chromosome region 12q22-q24.1 and mouse chromosome region 10C22D1. Cytogenet. Cell Genet. 56:178-81
139. Thompson AJ, Smith I, Kendall BE, Youll BD, Brenton D. 1991. MRI changes in early treated patients with phenylketonuria. Lancet 2:1224
140. Thompson AJ, Tillotson S, Smith I, Kendall B, Moore SG, et al. 1993. Brain MRI changes in phenylketunuria. Associations with dietary status. Brain 116: 811-21
141. Thompson GN, Francis DEM, Kirby DM, Compton R. 1991. Pregnancy in phenylketonuria: Dietary treatment aimed at normalizing maternal plasma phenylalanine concentration. Arch. Dis. Child. 66:1346-49
142. Thöny B, Heizmann CW, Mattei M-G. 1994. Chromosomal location of two human genes encoding tetrahydrobiopterin metabolizing enzymes: 6-pyruvoyl-tetrahydropterin synthase maps to 11q22.3-23.3, and pterin-4α-carbinolamine dehydratase maps to 10q22. Genomics 19:365-68
143. Thöny B, Leimbacher W, Blau N, Harvie A. Heizmann CW. 1994. Hyperphenylalaninemia due to defects in tetrahydropterin metabolism: Molecular characterization of mutations in 6-pyruvoyltetrahydropterin synthase. Am. J. Hum. Genet. 54:782-92
144. Thöny B, Leimbacher W, Bürgisser D, Heizmann CW. 1992. Human 6-pyrovoyltetrahydropterin synthase: cDNA cloning and heterologous expression of the recombinant enzyme. Biochem. Biophys. Res. Commun. 189: 1437-43
145. Thöny B. Neuheiser F, Hauer CR, Heizmann CW. 1993 Molecular cloning and recombination expression of the human liver phenylalanine hydroxylase stimulating factor revealed structural and function identify to the dimerization cofactor for the nuclear transcription factor HNF-1α. In Chemistry and Biology of Pteridines anil Folates, ed. JE Ayling, MG Nair, CM Baugh, pp. 103-6. New York: Plenum
146. Tipper J, Kaufman S. 1992. Phenylalanine-induced phosphorylation and activation of rat hepatic phenylalanine hydroxylase in vivo. J. Biol. Chem. 267: 889-96
147. Tolmie JL, Harvie A, Cockburn F. 1992. The teratogenic effects of undiagnosed maternal hyperphenylalaninaemia: a case for prevention? Br. J. Obstet. Gynocol. 99:347-48
148. Treacy E, Byck S, Clow C, Scriver CR. 1993. 'Celtic' phenylketonuria chromosomes found? Evidence in two regions of Quebec province. Eur. J. Hum. Genet. 1:220-28
149. Trefz FK, Burgard P, König T, Goebel-Schreiner B, Lichter-Konecki U, et al. 1993. Genotype-phenotype correlations in phenylketonuria. Clin. Chim. Acta 217:15-21
150. Vajro P, Strisciuglio P, Houssin D, Huault G, Laurent J, et al. 1993. Correction of phenylketonuria after liver transplantation in a child with cirrhosis. New Engl. J. Med. 329:363
151. 149. Varughese KI, Skinner MW, Whiteley JM, Matthews DA, Xuong NH. 1992. Crystal structure of rat liver dihydropteridine reductase. Proc. Natl. Acad. Sci. USA 89:6080-84
152. Vilaseca MA, Briones P, Ferrer I, Campistol J, Riverola A, et al. 1993. Controlled diet in phenylketonuria may cause serum carnitine deficiency. J. Inherit. Metab. Dis. 16:101-4
153. Villasana D, Butler IJ, Williams JC, Roongta SM. 1989. Neurological deterioration in adult phenylketonuria. J. Inherit. Metab. Dis. 12:451-57
154. Wang T, Okano Y, Eisensmith RC, Harvey ML, Lo WHY, et al. 1991. Founder effect of a prevalent PKU mutation in the Oriental population. Proc. Natl. Acad. Sci. USA 88:2146-50
155. Wang T, Okano Y, Eisensmith RC, Lo WHY, Huang S-Z, et al. 1991. Identification of a novel PKU mutation in Chinese: further evidence for multiple origins of PKU in Asia. Am. J. Hum. Genet. 48:628-30
156. Wang Y, DeMayo JL, Hahn TM, Finegold MJ, Konecki DS, et al. 1992. Tissue- and development-specific expression of the human phenylalanine hydroxylase/chloramphenicol acetyltransferase fusion gene in transgenic mice. J. Biol. Chem. 267:15105-10
157. Weglage J, Flinders B, Wilken B, Schubert D, Ullrich K. 1993. School performance and intellectual outcome in adolescents with phenylketonuria. Acta Pediatr. 81:582-86
158. Woolf LI. 1986. The heterozygote advantage of phenylketonuria. Am. J. Hum. Genet. 38:773-74