European Journal of Pediatrics

, Volume 149, Supplement 1, pp 25–27 | Cite as

Significance of the in vivo deuterated phenylalanine load for long-term phenylalanine tolerance and psychointellectual outcome in patients with PKU

  • F. K. Trefz
  • U. Batzler
  • T. König
  • Ute Michel
  • E. Schmidt
  • Hildgund Schmidt
  • H. Bickel
Article

Abstract

In 20 patients with PAH deficiency, in vivo RA was determined by an intravenous deuterated Phe load. Sixteen patients had RAs of less than 0.4% of normal, 3a clearly detectable activity between 0.8 and 1.4% of normal. Long-term Phe tolerance as measured by the distribution of plasma Phe levels in categories (0–3.9, 4.0–9.9, 10–15.9 and over 16 mg/dl) was much improved in patients with RAs greater than 0.8%. There was a negative correlation between RA and number of plasma Phe levels >16 mg/dl. Relationship between full scale IQ at the age of 9 years and dietary control showed a positive correlation between IQ and the number of Phe levels between 0–10 mg/dl (k=.50p<0.05). Highest (negative) correlation (k=−0.67p<0.007) was found between full scale IQ and the number of Phe values >16 mg/dl as measured over 9 years. On the one hand detectable RA of PAH reduces the risk of high Phe levels and thus may also reduce the risk of brain damage in untreated or suboptimally treated patients with PAH. On the other hand enzyme measurement of PAH is no predictive parameter for Phe tolerance in an individual patient since RA may be very similar in phenylketonuric/hyperphenylalaninaemic patients. For practical purposes the oral protein loading test at the age of 6 months will give the most reliable results for differential diagnosis of PAH deficiency.

Key words

PKU Phenylalanine hydroxylase Deuterated phenylalanine Psychointellectual outcome 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Blaskovics ME, Scheffler GE, Hack S (1974) Phenylalaninemia Differential diagnosis. Arch Dis Child 49:835–843PubMedGoogle Scholar
  2. 2.
    DiLella AG, Marvit J, Lidsky AS, Guettler F, Woo SLC (1986) Tight linkage between a splicing mutation and a specific DNA haplotype in phenylketonuria. Nature 322:799–803PubMedGoogle Scholar
  3. 3.
    DiLella AG, Marvit J, Brayton K, Woo SLC (1987) An amino acid substiution involved in phenylketonuria is in linkage disequilibrium with DNA haplotype 2. Nature 327:333–336PubMedGoogle Scholar
  4. 4.
    Guettler F (1980) Hyperphenylalaninemia: diagnosis and classification of the various types of phenylalanine hydroxylase deficiency in childhood. Acta Paediatr Scand [Suppl] 280:1–80Google Scholar
  5. 5.
    Holtzman NA, Dronmal RA, Van Doornick W, Azen CG, Koch R (1986) Effect of age at loss of dietary control on intellectual performance and behaviour of children with phenylketonuria. N Engl J Med 314:593–598PubMedGoogle Scholar
  6. 6.
    Lichter-Konecki U, Schlotter M, Konecki DS, Labeit S, Woo SLC, Trefz FK (1988) Linkage disequilibrium between mutation and RFLP haplotype at the phenylalanine hydroxylase locus in the German population. Hum Genet 78:347–352PubMedGoogle Scholar
  7. 7.
    Lichter-Konecki U, Konecki DS, DiLella AG, Brayton K, Marvit J, Trefz FK, Woo SLC (1988) Phenylalanine hydroxylase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase gene. Biochemistry 27:2881–2885PubMedGoogle Scholar
  8. 8.
    Lichter-Konecki U, Schlotter M, Trefz FK, Konecki DS (1989) Direct detection of a major mutation responsible for phenylketonuria in the German population. Eur J Pediatr 149:120–123PubMedGoogle Scholar
  9. 9.
    Lutz P, Schmidt H, Batzler U (1990) Study design and description of patients. Eur J Pediatr 149 [Suppl 1]:S5-S12PubMedGoogle Scholar
  10. 10.
    Lyonnet S, Caillaud C, Rey F, Berthelon M, Frezal J, Rey J, Munnich A (1989) Molecular genetics of phenylketonuria in Mediteranean countries: a mutation associated with partial phenylalanine hydroxylase deficiency. Am J Hum Genet 44:511–517PubMedGoogle Scholar
  11. 11.
    Michel U, Schmidt E, Batzler U (1990) Results of psychological testing of patients aged 3 to 6 years. Eur J Pediatr 149 [Suppl 1]: S34-S38PubMedGoogle Scholar
  12. 12.
    Scriver CR, Kaufman S, Woo SLC (1988) Mendelian hyperphenylalaninemia. Ann Rev Genet 22:301–321PubMedGoogle Scholar
  13. 13.
    Trefz FK, Byrd DJ, Blaskovics M, Lutz P, Kochen W (1976) Determination of deuterium labelled phenylalanine and tyrosine in human plasma with high pressure liquid chromatography and mass spectrometry. Clin Chim Acta 73:431–438PubMedGoogle Scholar
  14. 14.
    Trefz FK, Erlenmaier T, Hunneman DH, Bartholome K, Lutz P (1979) Sensitive in vivo assay of the phenylalanine hydroxylating system with a small intravenous dose of heptadeutero L-phenylalanine using high pressure liquid chromatography and capillary gas chromatography/mass fragmentography. Clin Chim Acta 99:211–220PubMedGoogle Scholar
  15. 15.
    Trefz FK, Bartholome K, Bickel H, Lutz P, Schmidt H, Seyberth HW (1981) In vivo residual activity of the phenylalanine hydroxylating system in phenylketonuria and variants. J Inherited Metab Dis 4:101–102PubMedGoogle Scholar
  16. 16.
    Trefz FK, Schmidt H, Bartholome K, Mahle K, Mahle M, Mathis P, Pecht G (1985) Differential diagnosis and significance of various hyperphenylalaninemias. In: Bickel H, Wachtel U (eds) Inherited diseases of amino acid metabolism recent progress in understanding, recognition and management. Thieme, Stuttgart, pp 86–100Google Scholar
  17. 17.
    Trefz FK, Lichter-Konecki U, Konecki DS, Schlotter M, Bickel H (1988) PKU and Non PKU Hyperphenylalaninemia: differentiation, indication for therapy and therapeutic results. Acta Paediatr Jpn 30:397–404PubMedGoogle Scholar
  18. 18.
    Trefz FK, Lichter-Konecki U, Konecki D (1989) Phenylketonuria. Current opinion in pediatrics 1:421–427Google Scholar
  19. 19.
    Waisbren SE, Mahon BE, Schnell RR, Harvey L, Levy MD (1987) Predictors of intelligence quotient and intelligence quotient change in persons treated for phenylketonuria early in life. Pediatrics 79:351–355PubMedGoogle Scholar
  20. 20.
    Woo SLC (1989) Molecular basis and population genetics of phenylketonuria. Biochemistry 28:1–6PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • F. K. Trefz
    • 1
  • U. Batzler
    • 1
  • T. König
    • 1
  • Ute Michel
    • 1
  • E. Schmidt
    • 1
  • Hildgund Schmidt
    • 1
  • H. Bickel
    • 1
  1. 1.KinderklinikRuprecht-Karls-Universität HeidelbergHeidelbergFederal Republic of Germany

Personalised recommendations