Human Genetics

, Volume 77, Issue 2, pp 168–171

Hyperphenylalaninemia due to deficiency of 6-pyruvoyl tetrahydropterin synthase

Unusual gene dosage effect in heterozygotes
  • C. R. Scriver
  • C. L. Clow
  • P. Kaplan
  • A. Niederwieser
Original Investigations

DOI: 10.1007/BF00272386

Cite this article as:
Scriver, C.R., Clow, C.L., Kaplan, P. et al. Hum Genet (1987) 77: 168. doi:10.1007/BF00272386

Summary

We have identified deficient biopterin synthesis in four probands and one sib with persistent postnatal hyperphenylalaninemia. The metabolic findings were associated with a benign clinical presentation and normal biopterin level in cerebrospinal fluid in the newborn period, indicating the peripheral (hepatic) form of this autosomal recessive phenotype. Impaired development was apparent at 3 months in one proband not treated early. Treatment with oral tetrahydropterin restored adequate phenylalanine hydroxylase activity; it also maintained or improved CNS function. The deficient enzyme in these subjects is 6-pyruvoyl tetrahydropterín synthase (PTS). Erythrocyte activity of PTS in homozygotes (or compound heterozygotes) is <10% of normal. Heterozygotes have 20%–50% of normal PTS activity (enzyme phenotype), a finding compatible with a range of gene dosage effects, some abnormal. The metabolic phenotype in heterozygotes (urine biopterin excretion) did not correlate with erythrocyte PTS activity. The complex relationship between erythrocyte PTS activity, and biopterin synthesis in these families indicates genetic heterogeneity at the PTS locus.

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • C. R. Scriver
    • 1
    • 2
  • C. L. Clow
    • 1
    • 2
  • P. Kaplan
    • 1
    • 2
  • A. Niederwieser
    • 3
  1. 1.Children's Hospital Research InstituteMcGill UniversityMontrealCanada
  2. 2.Quebec Network of Genetic MedicineMontrealCanada
  3. 3.Universitäts-KinderklinikZürichSwitzerland
  4. 4.deBelle Laboratory for Biochemical GeneticsMontreal Children's HospitalMontrealCanada

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