The Spectrum of Hypoxanthine-Guanine Phosphoribosyltransferase (HPRT) Deficiency
| Autor: | Felícitas A. Mateos, Juan G. Puig, Antonio Buño, Joaquín Arcas, Teresa H. Ramos, Rosa J. Torres |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Purine
Genetics Mutation medicine.medical_specialty Psychomotor retardation Choreoathetosis Disease medicine.disease_cause medicine.disease Gastroenterology chemistry.chemical_compound chemistry Hypoxanthine-guanine phosphoribosyltransferase Internal medicine medicine Spasticity medicine.symptom Lesch–Nyhan syndrome |
| Zdroj: | Purine and Pyrimidine Metabolism in Man X ISBN: 0306465159 |
| DOI: | 10.1007/0-306-46843-3_4 |
| Popis: | Summary The enzyme hypoxanthine-guanine phosphoribo-syltransferase (HPRT) catalyzes the reutilization ofhypoxanthine and guanine to the purine nucleotidesIMP and GMP, respectively. HPRT deficiency is an X-linked disorder characterized by uric acid over-production and variable neurologic impairment. Thecomplete deficiency of HPRT is diagnostic of Lesch-Nyhan syndrome manifested by choreoathetosis,spasticity, mental retardation, and self-injurious be-havior. In some HPRT-deficient patients the enzymedefect appeared to be “partial” and the neurologicsymptoms mild to severe (Kelley-Seegmiller syn-drome). This has prompted the classification ofHPRT deficiency in 2 distinct groups: Lesch-Nyhansyndrome and Kelley-Seegmiller syndrome, whichhas created much confusion. A spectrum of clinicalconsequences of HPRT deficiency has been recog-nized in small series of patients, but the completespectrum of the neurologic disorder has not been de-scribed in a single series of patients examined by thesame observers.We analyzed our experience with 22 patients be-longing to 18 different families with HPRT deficiencydiagnosed at “La Paz” University Hospital in Madridover the past 16 years. The clinical spectrum of theseHPRT-deficient Spanish patients was similar to thedifferent phenotypes occasionally reported in the lit-erature, in some cases diagnosed as Lesch-Nyhan“variants.” The clinical, biochemical, enzymatic, andmolecular genetic studies on these 22 patients al-lowed us to delineate a new classification of HPRTdeficiency. Based on the neurologic symptoms, de-pendency for personal care, HPRT activity in he-molysate and in intact erythrocytes, and predictedprotein size, patients were classified into 4 groups:Group 1 (2 patients), normal development with noneurologic symptoms, HPRT activity was detectablein hemolysates and in intact erythrocytes, and themutation did not affect the predicted protein size.Group 2 (3 patients) mild neurologic symptoms thatdid not prevent independent lives, HPRT activity wasdetectable in intact erythrocytes, and the protein sizewas normal. Group 3 (2 patients), severe neurologicimpairment that precluded an independent life, noresidual HPRT activity, and normal protein size.Group 4 (15 patients), clinical characteristics ofLesch-Nyhan syndrome (some may not show self-injurious behavior), no residual HPRT activity, and inmost (7 of 8 patients in whom the mutation could bedetected) the mutation affected the predicted pro-tein size.This classification of HPRT deficiency into 4groups may be more useful in terms of accuracy, re-producibility, assessment for treatment trials andprognosis. The study of this Spanish series allows usto conclude that HPRT deficiency may be manifestedby a wide spectrum of neurologic symptoms; theoverall severity of the disease is associated with mu-tations permitting some degree of residual enzymeactivity; and mutation analysis provides a valuable |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|