Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency: The Molecular Basis of the Clinical Syndromes

New England Journal of Medicine

Volumn 309, Issue 15, 1983, Pages 900-910

  Flier, Jeffrey S ^a   Moore, Mary Jean ^a   Wilson, James M ^b   Young, Anne B ^b   Kelley, William N ^b  

^a University of Michigan Medical School ^*

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RESTRICTION ENDONUCLEASE;

CENTRAL NERVOUS SYSTEM; CHILD; CONGENITAL DISORDER; DIAGNOSIS; ENZYME DEFICIENCY; ETIOLOGY; GENETIC ENGINEERING; HEREDITY; HUMAN; JOINT; LESCH NYHAN SYNDROME; REVIEW; X CHROMOSOME LINKAGE;

AMINO ACID SEQUENCE; BASAL GANGLIA; BRAIN CHEMISTRY; CHROMOSOME MAPPING; DNA; FEMALE; GENES; GOUT; HUMAN; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; KIDNEY CALCULI; LESCH-NYHAN SYNDROME; MALE; MUTATION; NEUROTRANSMITTERS; PROTEIN CONFORMATION; SUPPORT, U.S. GOV'T, P.H.S.; VARIATION (GENETICS);

EID: 0020960968     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJM198310133091507     Document Type: Review

References (87)

1. Seegmiller JE, Rosenbloom FM, Kelley WN. Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science 1967; 155: 1682–4.
2. Lesch M, Nyhan WL. A familial disorder of uric acid metabolism and central nervous system function. Am J Med 1964; 36: 561–70.
3. Kelley WN, Rosenbloom FM, Henderson JF, Seegmiller JE. A specific enzyme defect in gout associated with overproduction of uric acid. Proc Natl Acad Sci USA 1967; 57: 1735–9.
4. Kelley WN, Wyngaarden JB. Clinical syndromes associated with hypoxanthine-guanine phosphoribosyltransferase deficiency. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS, eds. The metabolic basis of inherited disease. 5th ed. New York: McGraw-Hill, 1983:1115–43.
5. Seegmiller JR. Diseases of purine and pyrimidine metabolism. In: Bondy PK, Rosenberg LE, eds. Metabolic control and disease. 8th ed. Philadelphia: WB Saunders, 1980:777–937.
6. Kelley WN, Greene ML, Rosenbloom FM, Henderson JF, Seegmiller JE. Hypoxanthine-guanine phosphoribosyltransferase deficiency in gout. Ann Intern Med 1969; 70: 155–206.
7. Muensch H, Yoshida A. Purification and characterization of human hypoxanthine/guanine phosphoribosyltransferase. Eur J Biochem 1977; 76: 107–12.
8. Olsen AS, Milman G. Human hypoxanthine phosphoribosyltransferase: purification and properties. Biochemistry 1977; 16: 2501–5.
9. Holden JA, Kelley WN. Human hypoxanthine-guanine phosphoribosyltransferase: evidence for tetrameric structure. J Biol Chem 1978; 253: 4459–63.
10. Johnson GG, Ramage AL, Littlefield JW, Kazazian HH Jr. Hypoxanthineguanine phosphoribosyltransferase in human erythroid cells: posttranslational modification. Biochemistry 1982; 21: 960–6.
11. Wilson JM, Tarr GE, Mahoney WC, Kelley WN. Human hypoxanthineguanine phosphoribosyltransferase: complete amino acid sequence of the erythrocyte enzyme. J Biol Chem 1982; 257: 10978–85.
12. Arnold WJ, Kelley WN. Human hypoxanthine-guanine phosphoribosyltransferase: purification and subunit structure. J Biol Chem 1971; 246: 7398–404.
13. Johnson GG, Eisenberg LR, Migeon BR. Human and mouse hypoxanthineguanine phosphoribosyltransferase: dimers and tetramers. Science 1979; 203: 174–6.
14. Arnold WJ, Kelley WN. Studies on the electrophoretic variants of human hypoxanthine-guanine phosphoribosyltransferase. In: Markert CL, ed. Isozymes. Vol. I. New York: Academic Press, 1975:213–25.
15. Zannis VI, Gudas LJ, Martin DW Jr. Characterization of the subunit composition of HGPRTase from human erythrocytes and cultured fibroblasts. Biochem Genet 1980; 18: 1–19.
16. Ghangas GS, Milman G. Hypoxanthine phosphoribosyltransferase: two-dimensional gels from normal and Lesch–Nyhan hemolyzates. Science 1977; 196: 1119–20.
17. Wilson JM, Baugher BW, Landa L, Kelley WN. Human hypoxanthineguanine phosphoribosyltransferase: purification and characterization of mutant forms of the enzyme. J Biol Chem 1981; 256: 10306–12.
18. Wilson JM, Landa LE. Kobayashi R, Kelley WN. Human hypoxanthineguanine phosphoribosyltransferases: tryptic peptides and post-translational modification of the erythrocyte enzyme. J Biol Chem 1982; 257: 14830–4.
19. Robinson AB. Evolution and the distribution of glutaminyl and asparaginyl residues in proteins. Proc Natl Acad Sci USA 1974; 71: 885–8.
20. Musick WDL. Structural features of the phosphoribosyltransferases and their relationship to human deficiency disorders of purine and pyrimidine metabolism. CRC Crit Rev Biochem 1981; 11: 1–34.
21. Piszkiewicz D, Tilley BE, Rand-Meir T, Parsons SM. Amino acid sequence of ATP phosphoribosyltransferases of Salmonella typhimurium. Proc Natl Acad Sci USA 1979; 76: 1589–92.
22. Tso JY, Zalkin H, van Cleemput M, Yanofsky C, Smith JM. Nucleotide sequence of Escherichia coli purF and deduced amino acid sequence of glutamine phosphoribosylpyrophosphate and amidotransferase. J Biol Chem 1982; 257: 3525–31.
23. Argos P, Hanei M, Wilson JM, Kelley WN. A possible nucleotide-binding domain in the tertiary fold of phosphoribosyltransferases. J Biol Chem 1983; 258: 6450–7.
24. Rossman MG, Liljas A, Brändén C-I, Banaszak LJ. Evolutionary and structural relationships among dehydrogenases. In: Boyer PD, ed. The enzymes. Vol. 11. Part A. New York: Academic Press. 1975:61–103.
25. Shapiro SL, Sheppard GL Jr, Dreifuss FE, Newcombe DS. X-linked recessive inheritance of a syndrome of mental retardation with hyperuricemia. Proc Soc Exp Biol Med 1966; 122: 609–11.
26. Nyhan WL, Pesek J, Sweetman L, Carpenter DG, Carter CH. Genetics of an X-linked disorder of uric acid metabolism and cerebral function. Pediatr Res 1967; 1: 5–13.
27. Ricciuti FC, Ruddle FH. Assignment of nucleoside phosphorylase to D-14 and localization of X-linked loci in man by somatic cell genetics. Nature [New Biol] 1973; 241: 180–2.
28. Becker MA, Yen RCK, Itkin P, Goss SJ, Seegmiller JE, Bakay B. Regional localization of the gene for human phosphoribosylpyrophosphate synthetase on the X chromosome. Science 1979; 203: 1016–9.
29. McKusick VA. The human genome through the eyes of a clinical geneticist. Cytogenet Cell Genet 1982; 32: 7–23.
30. Brennand J, Chinault Achéal, Konecki DS, Melton DW, Caskey CT. Cloned cDNA sequences of the hypoxanthine/guanine phosphoribosyltransferase gene from a mouse neuroblastoma cell line found to have amplified genomic sequences. Proc Natl Acad Sci USA 1982; 79: 1950–4.
31. Jolly DJ, Esty Achéal, Bernard HU, Friedmann T. Isolation of a genomic clone partially encoding human hypoxanthine phosphoribosyltransferase. Proc Natl Acad Sci USA 1982; 79: 5038–41.
32. Lin P, Yamaizumi M, Murphy PD, Egg A, Ruddle FH. Partial purification and characterization of the mRNA for human thymidine kinase and hypoxanthine/guanine phosphoribosyltransferase. Proc Natl Acad Sci USA 1982; 79: 4290–4.
33. Jolly DJ, Okayama H, Berg P, et al. Isolation and characterization of a full-length expressible cDNA for human hypoxanthine phosphoribosyltransferase. Proc Natl Acad Sci USA 1983; 80: 477–81.
34. McDonald JA, Kelley WN. Lesch–Nyhan syndrome: altered kinetic properties of mutant enzyme. Science 1971; 171: 689–91.
35. Kelley WN, Meade JC. Studies on hypoxanthine-guanine phosphoribosyltransferase in fibroblasts from patients with the Lesch–Nyhan syndrome: evidence for genetic heterogeneity. J Biol Chem 1971; 246: 2953–8.
36. Bakay B, Nyhan WL, Fawcett N, Kogut MD. Isoenzymes of hypoxanthineguanine-phosphoribosyl transferase in a family with partial deficiency of the enzyme. Biochem Genet 1972; 7: 73–85.
37. Benke PJ, Herrick N. Hebert A. Hypoxanthine-guanine phosphoribosyltransferase variant associated with accelerated purine synthesis. J Clin Invest 1973; 52: 2234–40.
38. Henderson JF, Dossetor JB, Dasgupta MK, Russell AS. Uric acid lithiasis associated with altered kinetics of hypoxanthine-guanine phosphoribosyltransferase. Clin Biochem 1976; 9: 4–8.
39. Sweetman L, Hoch MA, Bakay B, Borden M, Lesh P, Nyhan WL. A distinct human variant of hypoxanthine-guanine phosphoribosyl transferase. J Pediatr 1978; 92: 385–9.
40. Gutensohn W, Jahn H. Partial deficiency of hypoxanthine-phosphoribosyltransferase: evidence for a structural mutation in a patient with gout. Eur J Clin Invest 1979; 9: 43–7.
41. Fox IH, Dwosh IL, Marchant PJ, et al. Hypoxanthine-guanine phosphoribosyltransferase: characterization of a mutant in a patient with gout. J Clin Invest 1975; 56: 1239–49.
42. Fox IH, Lacroix S. Electrophoretic variation in the partial deficiency of hypoxanthine-guanine phosphoribosyltransferase. J Lab Clin Med 1977; 90: 25–9.
43. Arnold WJ, Meade JC, Kelley WN. Hypoxanthine-guanine phosphoribosyltransferase: characteristics of the mutant enzyme in erythrocytes from patients with the Lesch–Nyhan syndrome. J Clin Invest 1972; 51: 1805–12.
44. Wilson JM, Baugher BW, Mattes PM, Daddona PE, Kelley WN. Human hypoxanthine-guanine phosphoribosyltransferase: demonstration of structural variants in lymphoblastoid cells derived from patients with a deficiency of the enzyme. J Clin Invest 1982; 69: 706–15.
45. Tarr GE. Improved manual sequencing methods. Methods Enzymol 1977; 47: 335–57.
46. Krenitsky TA, Papaioannou R. Human hypoxanthine phosphoribosyltransferase. II. Kinetics and chemical modification. J Biol Chem 1969; 244: 1271–7.
47. Snyder FF, Cruikshank MK, Seegmiller JE. A comparison of purine metabolism and nucleotide pools in normal and hypoxanthine-guanine phosphoribosyltransferase-deficient neuroblastoma cells. Biochim Biophys Acta 1978; 543: 556–69.
48. Wilson JM, Kobayashi R, Fox IH, Kelley WN. Human hypoxanthineguanine phosphoribosyltransferase: molecular abnormality in a mutant form of the enzyme (HPRTToronto). J Biol Chem 1983; 258: 6458–60.
49. Wilson JM, Tarr GE, Kelley WN. Human hypoxanthine (guanine) phosphoribosyltransferase: an amino acid substitution in a mutant form of the enzyme isolated from a patient with gout. Proc Natl Acad Sci USA 1983; 80: 870–3.
50. Wilson JM, Kelley WN. Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in a patient with the Lesch-Nyhan syndrome. J Clin Invest 1983; 71: 1331–5.
51. Upchurch KS, Leyva A, Arnold WJ, Holmes EW, Kelley WN. Hypoxanthine phosphoribosyltransferase deficiency: association of reduced catalytic activity with reduced levels of immunologically detectable enzyme protein. Proc Natl Acad Sci USA 1975; 72: 4142–6.
52. Ghangas GS, Milman G. Radioimmune determination of hypoxanthine phosphoribosyltransferase crossreacting material in erythrocytes of Lesch–Nyhan patients. Proc Natl Acad Sci USA 1975; 72: 4147–50.
53. Rijksen G. Staal GEJ, van der Vlist MJM, et al. Partial hypoxanthineguanine phosphoribosyl transferase deficiency with full expression of the Lesch–Nyhan syndrome. Hum Genet 1981; 57: 39–47.
54. Konecki DS, Brennand J, Fuscoe JC, Caskey CT. Chinault Achéal. Hypoxanthine-guanine phosphoribosyltransferase genes of mouse and Chinese hamster: construction and sequence analysis of cDNA recombinants. Nucleic Acids Res 1982; 10: 6763–75.
55. Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 1975; 98: 503–17.
56. Nussbaum R, Brennand J, Chinault Achéal, et al. Molecular analysis of the hypoxanthine phosphoribosyltransferase locus. In: The Banbury Center report on the uses of recombinant DNA in the study of human diseases. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory, (in press).
57. Friedmann T, Esty A, Filpula D, Doolittle R, Jolly DJ. Characterization of an expressible HGPRT cDNA. In: The Banbury Center report on the uses of recombinant DNA in the study of human diseases. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory, (in press).
58. Kronenberg HM. Looking at genes. N Engl J Med 1983; 307: 50–2.
59. Nussbaum RL, Crowder WE, Nyhan WL, Caskey CT. A three allele restriction fragment length polymorphism at the hypoxanthine phosphoribosyltransferase locus in man. Proc Natl Acad Sci USA 1983; 80: 4035–9.
60. Wilson JM, Frossard P, Nussbaum R, Caskey CT, Kelley WN. Human hypoxanthine-guanine phosphoribosyltransferase: detection of a mutant allele by restriction endonuclease analysis. J Clin Invest (in press).
61. Rockson S, Stone R, van der Weyden M, Kelley WN. Lesch–Nyhan syndrome: evidence for abnormal adrenergic function. Science 1974; 186: 934–5.
62. Castells S, Chakrabarti C, Winsberg BG, Hurwic M, Perel JM, Nyhan WL. Effects of L-5-hydroxytryptophan on monoamine and amino acids turnover in the Lesch–Nyhan syndrome. J Autism Dev Disord 1979; 9: 95–103.
63. Anders TF, Cann HM, Ciaranello RD, Barchas JD, Berger PA. Further observations on the use of 5-hydroxytryptophan in a child with Lesch–Nyhan syndrome. Neuropaediatrie 1978; 9: 157–66.
64. Sass JK, Itabashi HH, Dexter RA. Juvenile gout with brain involvement. Arch Neurol 1965; 13: 639–55.
65. Crussi FG, Robertson DM, Hiscox JL. The pathological condition of the Lesch–Nyhan syndrome: report of two cases. Am J Dis Child 1969; 118: 501–6.
66. Mizuno T, Endoh H, Konishi Y, Miyachi Y, Akaoka I. An autopsy case of the Lesch–Nyhan syndrome: normal HGPRT activity in liver and xanthine calculi in various tissues. Neuropaediatrie 1976; 76: 351–5.
67. Lloyd KG, Homykiewicz O, Davidson L, et al. Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch–Nyhan syndrome. N Engl J Med 1981; 305: 1106–11.
68. Rassin DK, Lloyd KG, Kelley WN, Fox I. Decreased amino acids in various brain areas of patients with Lesch–Nyhan syndrome. Neuropediatrics 1982; 13: 130–4.
69. Fonnum F, Storm-Mathisen J, Divac I. Biochemical evidence for glutamate as neurotransmitter in corticostriatal and corticothalamic fibres in rat brain. Neuroscience 1981; 6: 863–73.
70. Young AB, Bromberg MB, Penney JB Jr. Decreased glutamate uptake in subcortical areas deafferented by sensorimotor cortical ablation in the cat. J Neurosci 1981; 1: 241–9.
71. Fonnum F, Gottesfeld Z, Grofova I. Distribution of glutamate decarboxylase, choline acetyltransferase and aromatic amino acid decarboxylase in the basal ganglia of normal and operated rats: evidence for striatopallidal. striatoentopeduncular and striatonigral GABAergic fibres. Brain Res 1978; 143: 125–38.
72. Nagy JL, Carter DA, Fibiger HC. Anterior striatal projections to the globus pallidus. entopeduncular nucleus and substantia nigra in the rat: the GABA connection. Brain Res 1978; 158: 15–29.
73. Hornykiewicz O. Brain neurotransmitter changes in Parkinson's disease. In: Marsden CD, Fahn S, eds. Neurology 2: movement disorders. London: Butterworths 1981:41–58.
74. Penney JB Jr, Young AB. Speculations on the functional anatomy of basal ganglia disorders. Annu Rev Neurosci 1983; 6: 73–94.
75. Barbeau A. Update on the biochemistry of Huntington's chorea. Adv Neurol 1979; 23: 449–61.
76. Spokes EGS. The neurochemistry of Huntington's chorea. Trends Neurosci 1981; 4: 115–8.
77. Tsukahara N. Synaptic plasticity in the mammalian central nervous system. Annu Rev Neurosci 1981; 4: 351–79.
78. Bird MT, Paulson GW. The rigid form of Huntington's chorea. Neurology (Minneap) 1971; 21: 271–6.
79. Johnston MV, Singer HS. Brain neurotransmitters and neuromodulators in pediatrics. Pediatrics 1982; 70: 57–68.
80. Rosenbloom FM, Kelley WN, Miller J, Henderson JF, Seegmiller JE. Inherited disorder of purine metabolism: correlation between central nervous system dysfunction and biochemical defects. JAMA 1967; 202: 175–7.
81. Skolnick P, Paul SM, Marangos PJ. Purines as endogenous ligands of the benzodiazepine receptor. Fed Proc 1980; 39: 3050–5.
82. Phillis JW. Diazepam potentiation of purinergic depression of central neurons. Can J Physiol Pharmacol 1979; 57: 432–5.
83. Daly JW, Bruns RF, Snyder SH. Adenosine receptors in the central nervous system: relationship to the central actions of methylxanthines. Life Sci 1981; 28: 2083–97.
84. Kopin IJ. Neurotransmitters and the Lesch–Nyhan syndrome. N Engl J Med 1981; 305: 1148–50.
85. Weatherall DJ, Clegg JB. Thalassemia revisited. Cell 1982; 29: 7–9.
86. McDonald JA, Kelley WN. Lesch-Nyhan syndrome: absence of the mutant enzyme in erythrocytes of a heterozygote for both normal and mutant hypoxanthine-guanine phosphoribosyl transferase. Biochem Genet 1972; 6: 21–6.
87. Van Woert MH, Yip LC, Balis ME. Purine phosphoribosyltransferase in Gilles de la Tourette syndrome. N Engl J Med 1977; 296: 210–2.