Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies

Molecular Genetics and Metabolism

Volumn 104, Issue SUPPL., 2011, Pages

  Blau, Nenad ^a,b,c   Hennermann, Julia B ^d   Langenbeck, Ulrich ^e   Lichter Konecki, Uta ^f  

^a UNIVERSITY CHILDREN S HOSPITAL   (Switzerland)

^b UNIVERSITY OF ZURICH   (Switzerland)

^c Research Center for Children RCC   (Switzerland)

^d CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^e UNIVERSITY HOSPITAL FRANKFURT   (Germany)

^f GEORGE WASHINGTON UNIVERSITY SCHOOL OF MEDICINE AND HEALTH SCIENCES   (United States)

Author keywords

BH4; Phenylketonuria; PKU; Tetrahydrobiopterin

Indexed keywords

AMINO ACID; BIOPTERIN; DIHYDROPTERIDINE REDUCTASE; NEOPTERIN; PHENYLALANINE; SAPROPTERIN; TETRAHYDROBIOPTERIN; TYROSINE;

ALLELE; CEREBROSPINAL FLUID ANALYSIS; DIFFERENTIAL DIAGNOSIS; DISEASE COURSE; GENE MUTATION; GENETIC ANALYSIS; GENOTYPE; HUMAN; HYPERPHENYLALANINEMIA; NEWBORN SCREENING; PHENOTYPE; PHENYLKETONURIA; PRIORITY JOURNAL; REVIEW; TANDEM MASS SPECTROMETRY; TETRAHYDROBIOPTERIN DEFICIENCY;

BIOPTERIN; GENETIC ASSOCIATION STUDIES; HUMANS; MUTATION; PHENYLKETONURIAS;

EID: 82755189438     PISSN: 10967192     EISSN: 10967206     Source Type: Journal    
DOI: 10.1016/j.ymgme.2011.08.017     Document Type: Review

References (56)

1. Dhondt J.L. Laboratory diagnosis of phenylketonuria. PKU and BH4: Advances in Phenylketonuria and Tetrahydrobiopterin 2006, 161-179. SPS Verlagsgesellschaft, Heilbronn. N. Blau (Ed.).
2. Guthrie R., Susi A. A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics 1963, 32:338-343.
3. Chace D.H., Sherwin J.E., Hillman S.L., Lorey F., Cunningham G.C. Use of phenylalanine-to-tyrosine ratio determined by tandem mass spectrometry to improve newborn screening for phenylketonuria of early discharge specimens collected in the first 24hours. Clin. Chem. 1998, 44:2405-2409.
4. Zaffanello M., Zamboni G., Maffeis C., Tato L. Neonatal birth parameters of positive newborns at PKU screening as predictors of false-positive and positive results at recall-testing. J. Med. Screen 2003, 10:181-183.
5. Phenylketonuria (PKU): screening and management. NIH Consens. Statement 2000, 17:1-33.
6. Eastman J.W., Sherwin J.E., Wong R., Liao C.L., Currier R.J., Lorey F., Cunningham G. Use of the phenylalanine:tyrosine ratio to test newborns for phenylketonuria in a large public health screening programme. J. Med. Screen 2000, 7:131-135.
7. Blau N., Thöny B., Cotton R.G.H., Hyland K. Disorders of tetrahydrobiopterin and related biogenic amines. The Metabolic and Molecular Bases of Inherited Disease 2001, 1725-1776. McGraw-Hill, New York. C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle, B. Childs, B. Vogelstein (Eds.).
8. Blau N., Van Spronsen F.J., Levy H.L. Phenylketonuria. Lancet 2010, 376:1417-1427.
9. Longo N. Disorders of biopterin metabolism. J. Inherit. Metab. Dis. 2009, 32:333-342.
10. Opladen T., Abu Seda B., Rassi A., Thöny B., Hoffmann G.F., Blau N. Diagnosis of tetrahydrobiopterin deficiency using filter paper blood spots: further development of the method and 5years experience. J. Inherit. Metab. Dis. 2011, 34:819-826.
11. Curtius H.C., Niederwieser A., Viscontini M., Otten A., Schaub J., Scheibenreiter S., Schmidt H. Atypical phenylketonuria due to tetrahydrobiopterin deficiency. Diagnosis and treatment with tetrahydrobiopterin, dihydrobiopterin and sepiapterin. Clin. Chim. Acta 1979, 93:251-262.
12. Ponzone A., Guardamagna O., Dianzani I., Ponzone R., Ferrero G.B., Spada M., Cotton R.G.H. Catalytic activity of tetrahydrobiopterin in dihydropteridine reductase deficiency and indications for treatment. Pediatr. Res. 1993, 33:125-128.
13. Muntau A.C., Röschinger W., Habich M., Demmelmair H., Hoffmann B., Sommerhoff C.P., Roscher A.A. Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria. N. Engl. J. Med. 2002, 347:2122-2132.
14. Bernegger C., Blau N. High frequency of tetrahydrobiopterin-responsiveness among hyperphenylalaninemias: a study of 1919 patients observed from 1988 to 2002. Mol. Genet. Metab. 2002, 77:304-313.
15. Fiege B., Blau N. Assessment of tetrahydrobiopterin (BH4)-responsiveness in phenylketonuria. J. Pediatr. 2007, 150:627-630.
16. Levy H., Milanowski A., Chakrapani A., Cleary M., Lee P., Trefz F.K., Whitley C.B., Feillet F., Feigenbaum A.S., Bebchuk J.D., Christ-Schmidt H., Dorenbaum A. Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomized placebo-controlled study. Lancet 2007, 370:504-510.
17. Blau N. Sapropterin dihydrochloride for phenylketonuria and tetrahydrobiopterin deficiency. Expert. Rev. Endocrinol. Metab. 2010, 5:483-494.
18. Levy H., Burton B., Cederbaum S., Scriver C. Recommendations for evaluation of responsiveness to tetrahydrobiopterin (BH(4)) in phenylketonuria and its use in treatment. Mol. Genet. Metab. 2007, 92:287-291.
19. Blau N. Defining tetrahydrobiopterin (BH4)-responsiveness in PKU. J. Inherit. Metab. Dis. 2008, 31:2-3.
20. Burton B.K., Grange D.K., Milanowski A., Vockley G., Feillet F., Crombez E.A., Abadie V., Harding C.O., Cederbaum S., Dobbelaere D., Smith A., Dorenbaum A. The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study. J. Inherit. Metab. Dis. 2007, 30:700-707.
21. Zurflüh M.R., Zschocke J., Lindner M., Feillet F., Chery C., Burlina A., Stevens R., Thöny B., Blau N. Molecular genetics of tetrahydrobiopterin responsive phenylalanine hydroxylase deficiency. Hum. Mutat. 2008, 29:167-175.
22. Dobrowolski S.F., Heintz C., Miller T., Ellingson C.R., Ellingson C.C., Özer I., Gökcay G., Baykal T., Thöny B., Demirkol M., Blau N. Molecular genetics and impact of residual in vitro phenylalanine hydroxylase activity on tetrahydrobiopterin-responsiveness in Turkish PKU population. Mol. Genet. Metab. 2011, 10:116-121.
23. N. Blau, U. Langenbeck, J.B. Hennermann, U. Lichter Konecki, Diagnosis and management of PKU: an international survey J Inherit Metab Dis (abstract), 34 (Suppl 3) (2011) S97.
24. Hyland K., Surtees R.A.H., Heales S.J.R., Bowron A., Howells D.W., Smith I. Cerebrospinal fluid concentrations of pterins and metabolites of serotonin and dopamine in a pediatric reference population. Pediatr. Res. 1993, 34:10-14.
25. Zorzi G., Thöny B., Blau N. Reduced nitric oxide metabolites in CSF of patients with tetrahydrobiopterin deficiency. J. Neurochem. 2002, 80:362-364.
26. Jäggi L., Zurflüh M.R., Schuler A., Ponzone A., Porta F., Fiori L., Giovannini M., Santer R., Hoffmann G.F., Ibel H., Wendel U., Ballhausen D., Baumgartner M.R., Blau N. Outcome and long-term follow-up of 36 patients with tetrahydrobiopterin deficiency. Mol. Genet. Metab. 2008, 93:295-305.
27. Driscoll K.W., Hsia D.Y., Knox W.E., Troll W. Detection by phenylalanine tolerance tests of heterozygous carriers of phenylketonuria. Nature 1956, 178:1239-1240.
28. Woo S.L., Lidsky A.S., Güttler F., Chandra T., Robson K.J. Cloned human phenylalanine hydroxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria. Nature 1983, 306:151-155.
29. Güttler F. Hyperphenylalaninemia: diagnosis and classification of the various types of phenylalanine hydroxylase deficiency in childhood. Acta Paediatr. Scand. Suppl. 1980, 280:1-80.
30. Lehmann W.D., Fischer R., Heinrich H.C., Clemens P., Grüttner R. Metabolic conversion of L-[U-14C]phenylalanine to respiratory 14CO2 in healthy subjects, phenylketonuria heterozygotes and classic phenylketonurics. Clin. Chim. Acta 1986, 157:253-266.
31. Hsieh M.C., Berry H.K., Bofinger M.K., Phillips P.J., Guilfoile M.B., Hunt M.M. Comparative diagnostic value of phenylalanine challenge and phenylalanine hydroxylase activity in phenylketonuria. Clin. Genet. 1983, 23:415-421.
32. Blaskovics M.E. Phenylketonuria: loading studies revisited. PKU and BH4: Advances in Phenylketonuria and Tetrahydrobiopterin 2006, 104-119. SPS Verlagsgesellschaft, Heilbronn. N. Blau (Ed.).
33. O'Flynn M.E., Holtzman N.A., Blaskovics M., Azen C., Williamson M.L. The diagnosis of phenylketonuria: a report from the Collaborative Study of Children Treated for Phenylketonuria. Am. J. Dis. Child. 1980, 134:769-774.
34. Lutz P., Schmidt H., Batzler U. Study design and description of patients. Eur. J. Pediatr. 1990, 149(Suppl 1):S5-S12.
35. Weglage J., Pietsch M., Feldmann R., Koch H.G., Zschocke J., Hoffmann G., Muntau-Heger A., Denecke J., Guldberg P., Güttler F., Möller H., Wendel U., Ullrich K., Harms E. Normal clinical outcome in untreated subjects with mild hyperphenylalaninemia. Pediatr. Res. 2001, 49:532-536.
36. Langenbeck U., Burgard P., Wendel U., Lindner M., Zschocke J. Metabolic phenotypes of phenylketonuria. Kinetic and molecular evaluation of the Blaskovics protein loading test. J. Inherit. Metab. Dis. 2009, 32:506-513.
37. Donlon J., Levy H., Scriver C.R. Hyperphenylalaninemia: phenylalanine hydroxylase deficiency. The Online Metabolic & Molecular Bases of Inherited Disease 2008, McGraw-Hill, Montreal, Ch. 77. D. Valle, A.L. Beaudet, B. Vogelstein, K.W. Kinzler, S.E. Antonarakis, A. Ballabio (Eds.).
38. Guldberg P., Rey F., Zschocke J., Romano V., Francois B., Michiels L., Ullrich K., Hoffmann G.F., Burgard P., Schmidt H., Meli C., Riva E., Dianzani I., Ponzone A., Rey J., Güttler F. A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype. Am. J. Hum. Genet. 1998, 63:71-79.
39. Guldberg P., Güttler F. Mutations in the phenylalanine hydroxylase gene: methods for their characterization. Acta Paediatr. Suppl. 1994, 407:27-33.
40. Kure S., Hou D.C., Ohura T., Iwamoto H., Suzuki S., Sugiyama N., Sakamoto O., Fujii K., Matsubara Y., Narisawa K. Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. J. Pediatr. 1999, 135:375-378.
41. van Spronsen F.J., van Rijn M., Dorgelo B., Hoeksma M., Bosch A.M., Mulder M.F., de Klerk J.B., de Koning T., Rubio-Gozalbo M.E., de Vries M., Verkerk P.H. Phenylalanine tolerance can already reliably be assessed at the age of 2years in patients with PKU. J. Inherit. Metab. Dis. 2009, 32:27-31.
42. MacLeod E.L., Gleason S.T., van Calcar S.C., Ney D.M. Reassessment of phenylalanine tolerance in adults with phenylketonuria is needed as body mass changes. Mol. Genet. Metab. 2009, 98:331-337.
43. Anastasoaie V., Kurzius L., Forbes P., Waisbren S. Stability of blood phenylalanine levels and IQ in children with phenylketonuria. Mol. Genet. Metab. 2008, 95:17-20.
44. Humphrey M., Nation J., Francis I., Boneh A. Effect of tetrahydrobiopterin on Phe/Tyr ratios and variation in Phe levels in tetrahydrobiopterin responsive PKU patients. Mol. Genet. Metab. 2011, 10.1016/j.ymgme.2011.1005.1011.
45. Güttler F., Guldberg P. The influence of mutations on enzyme activity and phenylalanine tolerance in phenylalanine hydroxylase deficiency. Eur. J. Pediatr. 1996, 155:S 6-S 10.
46. Langenbeck U., Zschocke J., Wendel U., Hönig V. Modelling the phenylalanine blood level response during treatment of phenylketonuria. J. Inherit. Metab. Dis. 2001, 24:805-814.
47. Fomon S.J., Haschke F., Ziegler E.E., Nelson S.E. Body composition of reference children from birth to age 10years. Am. J. Clin. Nutr. 1982, 35:1169-1175.
48. Burton B.K., Leviton L. Reaching out to the lost generation of adults with early-treated phenylketonuria (PKU). Mol. Genet. Metab. 2010, 101:146-148.
49. U. Langenbeck, M. Ammar, J. Zschocke, E. Solem, I.M. Knerr, J. Herwig, H. Boehles, Recognizing catabolic states during dietary treatment of phenylketonuria. An application of metabolic modelling J Inherit Metab Dis 34 (Suppl 3) (2011) S102.
50. Wendel U., Langenbeck U. Towards self-monitoring and self-treatment in phenylketonuria-a way to better diet compliance. Eur. J. Pediatr. 1996, 155(Suppl 1):S105-S107.
51. Konecki D.S., Lichter Konecki U. The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations. Hum. Genet. 1991, 87:377-388.
52. Eisensmith R.C., Okano Y., Dasovich M., Wang T., Güttler F., Lou H., Guldberg P., Lichter-Konecki U., Konecki D.S., Svensson E., et al. Multiple origins for phenylketonuria in Europe. Am. J. Hum. Genet. 1992, 51:1355-1365.
53. Hoang L., Byck S., Prevost L., Scriver C.R. PAH mutation analysis consortium database - a database for disease-producing and other allelic variation at the human PAH locus. Nucleic Acids Res. 1996, 24:127-131.
54. Okano Y., Eisensmith R.C., Güttler F., Lichter-Konecki U., Konecki D.S., Trefz F.K., Dasovich M., Wang T., Henriksen K., Lou H., et al. Molecular basis of phenotypic heterogeneity in phenylketonuria. N. Engl. J. Med. 1991, 324:1232-1238.
55. Kaufman S. Phenylketonuria: Biochemical Mechanisms 1976, Advances in Neurochemistry, Plenum Press, New York, 1976, pp. 1-132. B.W. Agranoff, M.H. Aprison (Eds.).
56. Waters P.J. How PAH gene mutations cause hyper-phenylalaninemia and why mechanism matters: insights from in vitro expression. Hum. Mutat. 2003, 21:357-369.