Journal of Inherited Metabolic Disease

, Volume 31, Supplement 2, pp 193–197 | Cite as

Serum prolactin as a tool for the follow-up of treated DHPR-deficient patients

  • D. Concolino
  • G. Muzzi
  • M. Rapsomaniki
  • M. T. Moricca
  • M. G. Pascale
  • P. Strisciuglio
Short Report


Deficiency of dihydropteridine reductase causes a variant form of phenylketonuria associated with a devastating neurological disease characterized by mental retardation, hypokinesis and other features relating to basal ganglia disorder. Hyperphenylalaninaemias with tetrahydrobiopterin deficiency make up about 1–3% of all hyperphenylalaninaemias. We describe three patients from Calabria, a southern region of Italy, who have a dihydropteridine reductase deficiency, caused by the same mutation (p.L14P) also found in the nearby region of Sicily. We report the evolution of clinical and biochemical data during the treatment of these patients where we used prolactin serum determination to adapt the specific therapy. This report suggests that serum prolactin levels can be a good biomarker for optimal dosage of hydroxylated precursors in long-term treatment monitoring.


Prolactin Neopterin Serum Prolactin Serum Prolactin Level Carbidopa 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





cerebrospinal fluid


dihydropteridine reductase


development quotient


dihydropteridine reductase gene


5-hydroxindoleacetic acid






homovanillic acid









We thank the John F. Kennedy Instituttet – Statens Øjenklinik (DK) for performing molecular analyses in our patients. We would like to thank in particular Dr Moller, PhD and Dr Nielsen, MD, for their kind cooperation.


  1. Blau N, Heizmann CW, Sperl W et al (1992) Atypical (mild) form of dihydropteridine reductase deficiency: neurochemical evaluation and mutation detection. Pediatr Res 32: 726–730.PubMedCrossRefGoogle Scholar
  2. Dahl HHM, Hutchinson W, McAdam W, Wake S, Morgan FJ, Cotton RGH (1987) Human dihydropteridine reductase: Characterization of a cDNA clone and its use in analysis of patients with dihydropteridine reductase deficiency. Nucleid Acids Res 15: 1921–1932.CrossRefGoogle Scholar
  3. Danks DM, Schlesinger P, Firgaira F et al (1979) Malignant hyperphenylalaninemia—clinical features, biochemical findings, and experience with administration of biopterins. Pediatr Res 13: 1150–1155.PubMedCrossRefGoogle Scholar
  4. de Sanctis L, Alliaudi C, Spada M et al (2000) Genotype–phenotype correlation in dihydropteridine reductase deficiency. J Inherit Metab Dis 23: 333–337.PubMedCrossRefGoogle Scholar
  5. Dianzani I, Howells DW, Ponzone A, Saleeba JA, Smooker PM, Cotton RGH (1993) Two new mutations in the dihydropteridine reductase gene in patients with tetrahydrobiopterin deficiency. J Med Genet 30: 465–469.PubMedCrossRefGoogle Scholar
  6. Dianzani I, de Sanctis L, Smooker PM et al (1998) Dihydropteridine reductase deficiency: Physical structure of the QDPR gene, identification of two new mutations and genotype-phenotype correlations. Hum Mutat 12: 267–273.PubMedCrossRefGoogle Scholar
  7. Howells DW, Forrest SM, Dahl HHM, Cotton RGH (1990) Insertion of an extra codon for threonine is a cause of dihydropteridine reductase deficiency. Am J Hum Genet 47: 279–285.PubMedGoogle Scholar
  8. Ikeda H, Matsubara Y, Mikami H et al (1997) Molecular analysis of dihydropteridine reductase deficiency: identification of two novel mutations in Japanese patients. Hum Genet 100: 637–642.PubMedCrossRefGoogle Scholar
  9. Lockier J, Cok RG, Milstein S, Kaufman S, Woo SL, Ledley FD (1987) Structure and expression of human dihydropteridine reductase. Proc Natl Acad Sci USA 84: 3329–3333.CrossRefGoogle Scholar
  10. Ponzone A, Ricca V, Ferraris S, Guardamagna O (1984) DHPR deficiency in Italy [Letter]. J Pediatr 105: 1008.PubMedCrossRefGoogle Scholar
  11. Ponzone A, Spada M, Ferraris S, Dianzani I, de Sanctis L (2004) Dihydropteridine reductase deficiency in man: from biology to treatment. Med Res Rev 24: 127–150.PubMedCrossRefGoogle Scholar
  12. Smooker PM, Cotton RGH (1995) Molecular basis of dihydropteridine reductase deficiency. Hum Mutat 5: 279–284.PubMedCrossRefGoogle Scholar
  13. Smooker PM, Howells DW, Cotton RGH (1993) Identification and in vitro expression of mutation causing dihydropteridine reductase deficiency. Biochemistry 32: 6443–6449.PubMedCrossRefGoogle Scholar
  14. Smooker PM, Gough TJ, Cotton RG, Alliaudi C, de Sanctis L, Dianzani I (1999) A series of mutations in the dihydropteridine reductase gene resulting in either abnormal RNA splicing or DHPR protein defects. Hum Mutat 13: 503–504.PubMedCrossRefGoogle Scholar
  15. Spada M, Ferraris S, Ferrero GB et al (1996) Monitoring treatment in tetrahydrobiopterin deficiency by serum prolactin. J Inherit Metab Dis 19: 231–233.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • D. Concolino
    • 1
  • G. Muzzi
    • 1
  • M. Rapsomaniki
    • 1
  • M. T. Moricca
    • 1
  • M. G. Pascale
    • 1
  • P. Strisciuglio
    • 1
  1. 1.Department of PediatricsUniversity ‘Magna Graecia’ of CatanzaroCatanzaroItaly

Personalised recommendations