Human Genetics

, Volume 57, Issue 1, pp 39–47 | Cite as

Partial hypoxanthine-guanine phosphoribosyl transferase deficiency with full expression of the Lesch-Nyhan syndrome

  • Gert Rijksen
  • Gerard E. J. Staal
  • Margreet J. M. van der Vlist
  • Frits A. Beemer
  • Jaap Troost
  • Wolf Gutensohn
  • Jan P. R. M. van Laarhoven
  • Chris H. M. M. de Bruyn
Original Investigations


A patient with the full clinical expression of the classical Lesch-Nyhan syndrome is presented with a residual hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity of 5–10% in erythrocyte lysate and about 30% in fibroblast lysate. The activities of other erythrocyte enzymes of purine metabolism were typical for a classical Lesch-Nyhan patient. The effects of allopurinol therapy on the excretion of urinary purine metabolites were studied by a newly developed isotachophoretic technique.

The unusually high residual activity of HGPRT in erythrodytes and fibroblasts of the patient enabled the enzymologic characterization of the mutant enzyme: in fibroblasts the affinities for the substrates hypoxanthine and guanine were normal. However, there was an increased apparent Km for phosphoribosylpyrophosphate (PRPP), a complete absence of product inhibition by IMP and GMP, and a decreased heat stability. Addition of PRPP did not stabilize the mutant enzyme. In addition to the altered properties of the fibroblast enzyme, the Km of the erythrocyte enzyme for hypoxanthine was also increased.

Immunoprecipitation experiments revealed the presence of an approximately normal amount of material cross-reacting with anti-human HGPRT antiserum. However, it appeared that this cross-reacting material had a decreased stability. When intact erythrocytes were incubated with radiolabeled purine bases, no formation of IMP or GMP could be detected, despite the relatively high residual activity of HGPRT in the hemolysate. The results fit the following hypothesis: as a consequence of a structural mutation affecting the PRPP-site of the enzyme and a decreased heat stability, the activity of the mutant enzyme under in vivo conditions is virtually zero.

In the erythrocytes of the patient's mother a normal HGPRT-activity was found. However, the activity in her fibroblasts was lower than normal, while a decreased heat stability and an intermediate behavior towards IMP could be shown.

Hair root analysis of several members of the patient's family confirmed the heterozygosity of the mother, whereas no other heterozygotes could be detected. The family anamnesis did not show other cases of Lesch-Nyhan syndrome. These findings were taken as evidence that the patient described in this paper might represent a mutation orginating from the gametes in either of the maternal grandparents.


Allopurinol Mutant Enzyme Phosphoribosylpyrophosphate Maternal Grandparent Erythrocyte Enzyme 
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.


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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • Gert Rijksen
    • 1
  • Gerard E. J. Staal
    • 1
  • Margreet J. M. van der Vlist
    • 1
  • Frits A. Beemer
    • 2
  • Jaap Troost
    • 3
  • Wolf Gutensohn
    • 4
  • Jan P. R. M. van Laarhoven
    • 5
  • Chris H. M. M. de Bruyn
    • 5
  1. 1.Department of Medical EnzymologyState University HospitalUtrechtThe Netherlands
  2. 2.Het Wilhelmina KinderziekenhuisUniversity Children's HospitalUtrechtThe Netherlands
  3. 3.Department of Child NeurologyState University HospitalUtrechtThe Netherlands
  4. 4.Institut für Anthropologie und Humangenetik der Universität MünchenMünchenFederal Republic of Germany
  5. 5.Department of Human Genetics, Faculty of MedicineUniversity of NijmegenThe Netherlands

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