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European Journal of Pediatrics

, Volume 149, Issue 10, pp 713–715 | Cite as

Neuroblastoma in a patient with dihydropteridine reductase deficiency

  • L. G. Greeves
  • R. J. Leeming
  • K. Hyland
  • S. I. Dempsey
  • D. J. Carson
Metabolic Diseases
  • 25 Downloads

Abstract

Tetrahydrobiopterin (BH4) deficiency is a rare cause of hyperphenylalaninaemia (HPA) and usually leads to progressive neurological deterioration despite early dietary control of plasma phenylalanine concentrations. Dihydropteridine reductase (DHPR) deficiency is the most severe cause with respect to a fatal outcome. We report a 7-year-old girl with HPA diagnosed on neonatal Guthrie screening who at the age of 6 months had cytotoxic therapy for an adrenal neuroblastoma which secreted catecholamines. When 4 years old she was found to have DHPR deficiency. Although developmentally retarded and microcephalic she has failed to develop the florid neurological features often associated with the condition.

Key words

Hyperphenylalaninaemia Dihydropteridine reductase Neuroblastoma Microcephaly 

Abbreviations

BH4

tetrahydrobiopterin

DHPR

dihydropteridine reductase

5-HIAA

5-Hydroxyindoleacetic acid

HPA

hyperphenylalaninaemia

HVA

homovanillic acid

PHE

phenylalanine

VMA

vanillylmandelic acid

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References

  1. 1.
    Albrecht AM, Biedler JL, Baker H, Frank O, Hutner SH (1978) Biopterin content of human neuroblastoma cells in culture. Chem Pathol Pharmacol 19: 377–380Google Scholar
  2. 2.
    Bartholome K, Byrd DJ, Kaufman S, Milstien S (1977) Atypical phenylketonuria with normal phenylalanine hydroxylase and dihydropteridine reductase activity in vitro. Pediatrics 59: 757–761PubMedGoogle Scholar
  3. 3.
    Brautigam M, Dreesen R, Herken H (1984) Tetrahydrobiopterin and total biopterin content of neuroblastoma (NIE-115, N2A) and phaeochromocytoma (PC-12) clones and the dependence of catecholamine synthesis on tetrahydrobiopterin concentration in PC-12 cells. J Neurochem 42: 390–396PubMedGoogle Scholar
  4. 4.
    Butler IJ, Koslow SH, Krumholz A, Holtzman NA, Kaufman S (1978) A disorder of biogenic amines in dihydropteridine reductase deficiency. Ann Neurol 3: 224–230CrossRefPubMedGoogle Scholar
  5. 5.
    Curtius HC, Niederwieser A, Viscontini M, Leimbacher W, Wegman H, Blehova B, Rey F, Schaut J, Schmidt H (1981) Serotonin and dopamine synthesis in phenylketonuria. Adv Exp Med Biol 33: 277–291Google Scholar
  6. 6.
    Danks DM, Bartholome K, Clayton BE, Curtius HC, Grobe H, Kaufman S, Leeming RJ, Pfleiderer W, Rembold H, Rey F (1978) Malignant hyperphenylalaninaemia-current status. J Inherited Metab Dis 1: 49–53CrossRefPubMedGoogle Scholar
  7. 7.
    Dhondt JI (1984) Tetrahydrobiopterin deficiences: Preliminary analysis from an international survey. J Pediatr 104: 501–508PubMedGoogle Scholar
  8. 8.
    Hyland K (1985) Estimation of tetrahydro, dihydro and fully oxidised pterins by high-performance liquid chromatography using sequential electrochemical and fluorescence detection. J Chromatogr 343: 35–41PubMedGoogle Scholar
  9. 9.
    Howells DW, Smith I, Leonard JV, Hyland K (1986) Tetrahydrobiopterin in dihydropteridine reductase deficiency. N Engl J Med 314: 520–521Google Scholar
  10. 10.
    Joseph MH, Lofthouse R (1986) The preservation of whole blood serotonin (5HT) and its determination using HPLC. In: Bender DA, Joseph MH, Kochen W, Steinhart H (eds) Progress in tryptophan research. de Gruyter, New York, pp 385–388Google Scholar
  11. 11.
    Kaufman S (1967) Metabolism of the phenylalanine hydroxylase cofactor. J Biol Chem 242: 3934–3943PubMedGoogle Scholar
  12. 12.
    Kaufman S (1981) Regulatory properties of pterin dependent hydrxylases: variations on a theme. In: Usdin E, Weiner N, Youdin MBH (eds) Function and regulation of monoamine enzymes. McMillan, New York, pp 165–173Google Scholar
  13. 13.
    Kaufman S, Holtzman NA, Milstien S, Butler IJ, Krumholz A (1975) Phenylketonuria due to a deficiency of dihydropteridine reductase. N Engl J Med 293: 785–790PubMedGoogle Scholar
  14. 14.
    Leeming RJ, Barford PA, Blair JA, Smith I (1984) Blood spots on Guthrie cards can be used for inherited tetrahydrobiopterin deficiency screening in hyperphenylalaninaemic infants. Arch Dis Child 59: 58–61PubMedGoogle Scholar
  15. 15.
    Matthews RG, Kaufman S (1980) Characterisation of the dihydropteridine reductase activity of methylenetetrahydrofolate reductase. J Biol Chem 255: 6014–6017PubMedGoogle Scholar
  16. 16.
    Niederwieser A, Blau N, Wang M, Joller R, Atares M, Cardesa-Garcia J (1984) GTP cyclohydrolase I deficiency, a new enzyme defect causeing hyperphenylalaninaemia with neopterin, biopterin, dopamine and serotonin deficiencies and muscular hypotonia. Eur J Pediatr 141: 208–214CrossRefPubMedGoogle Scholar
  17. 17.
    Niederwieser A, Leimbacher W, Curtius HC, Ponzone A, Rey F, Leupold D (1985) Atypical phenylketonuria with dihydrobiopterin sythetase deficiency: absence of phosphate eliminating enzyme activity demonstrated in liver. Eur J Pediatr 144: 13–16CrossRefPubMedGoogle Scholar
  18. 18.
    Pollock RJ, Kaufman S (1978) Dihydropteridine reductase may function in tetrahydrofolate metabolism. J Neurochem 31: 115–123PubMedGoogle Scholar
  19. 19.
    Rey F, Harpey JP, Leeming RJ, Blair JA, Aicardi J, Rey J (1977) Les hyperphenylalaninemies avex activite normale de la phenylalanine hydroxylase: le deficit en tetrahydrobiopterine et le deficit en dihydropteridine reductase. Arch Fr Pediatr 34: CIX-CXXPubMedGoogle Scholar
  20. 20.
    Richards DA, Titheradge AC (1987) Simultaneous liquid chromatographic determination of vanillymandelic acid, homovanillic acid and 5-hydroxy-3-indoleacetic acid in urine using isocratic elution and electrochemical detection. Biomed Chromatogr 2: 115–119CrossRefPubMedGoogle Scholar
  21. 21.
    Smith I, Hyland K, Kendall B, Leeming R (1985) Clinical role of pteridine therapy in tetrahydrobiopterin deficiency. J Inherited Metab Dis 8 [Suppl 1]: 39–45CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • L. G. Greeves
    • 1
  • R. J. Leeming
    • 2
  • K. Hyland
    • 3
  • S. I. Dempsey
    • 1
  • D. J. Carson
    • 4
  1. 1.Royal Belfast Hospital for Sick ChildrenBelfastNorthern Ireland
  2. 2.Department of HaematologyThe General HospitalBirminghamUK
  3. 3.Department of Child HealthInstitute of Child HealthLondonUK
  4. 4.Department of Child Health, Institute of Clinical ScienceThe Queen's UniversityBelfastNorthern Ireland

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