Disorders of purine and pyrimidine metabolism

Inborn Metabolic Diseases: Diagnosis and Treatment

Volumn , Issue , 2012, Pages 499-518

  Van Den Berghe, Georges ^a   Vincent, M Francoise ^b   Marie, Sandrine ^b  

^a DE DUVE INSTITUTE   (Belgium)

^b CLINIQUES UNIVERSITAIRES SAINT LUC   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84956620031     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-3-642-15720-2_36     Document Type: Chapter

References (124)

1. Sperling O, Boer P, Persky-Brosh S et al. (1972) Altered kinetic property of erythrocyte phosphoribosylpyrophosphate synthetase in excessive purine production. Rev Eur Etud Clin Biol 17:703-706
2. Becker MA, Puig JG, Mateos FA et al. (1988) Inherited superactivity of phosphoribosylpyrophosphate synthetase: association of uric acid overproduction and sensorineural deafness. Am J Med 85:383-390
3. Becker MA (2001) Phosphoribosylpyrophosphate synthetase and the regulation of phosphoribosylpyrophosphate production in human cells. Prog Nucl Acid Res Mol Biol 69:115-148
4. De Brouwer APM, Bokhoven v H, Nabuurs SB et al. (2010) PRPS1 Mutations: four distinct syndromes and potential treatment. Am J Hum Genet 86:506-518
5. Kranen S, Keough D, Gordon RB, Emmerson BT (1985) Xanthinecontaining calculi during allopurinol therapy. J Urol 133:658-659
6. Jaeken J, Berghe v d G (1984) An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids. Lancet 2:1058-1061
7. Jaeken J, Wadman SK, Duran M et al. (1988) Adenylosuccinase deficiency: an inborn error of purine nucleotide synthesis. Eur J Pediatr 148:126-131
8. Bergh v d FAJTM, Bosschaart AN, Hageman G et al. (1998) Adenylosuccinase deficiency with neonatal onset severe epileptic seizures and sudden death. Neuropediatrics 29:51-53
9. Mouchegh K, Zikanova M, Hoffmann GF et al. (2007) Lethal fetal and early postnatal presentation of adenylosuccinate lyase deficiency: observation of 6 patients in 4 families. J. Pediatr 150:57-61
10. Valik D, Miner PT, Jones JD (1997) First U.S. case of adenylosuccinate lyase deficiency with severe hypotonia. Pediatr Neurol 16:252-255
11. Spiegel EK, Colman RF, Patterson D (2006) Adenylosuccinate lyase deficiency. Mol Genet Metab 89:19-31
12. Gitiaux C, Ceballos-Picot I, Marie S et al. (2009) Misleading behavioural phenotype with adenylosuccinate lyase deficiency. Eur J Hum Genet 17:133-136
13. Mierzewska H, Schmidt-Sidor B, Jurkiewicz E et al. (2009) Severe encephalopathy with brain atrophy and hypomyelination due to adenylosuccinate lyase deficiency – MRI, clinical, biochemical and neuropathological findings of Polish patients. Folia Neuropathol 4:314-320
14. Berghe v d G, Vincent MF, Jaeken J (1997) Inborn errors of the purine nucleotide cycle: adenylosuccinase deficiency. J Inherit Metab Dis 20:193-202
15. Stone RL, Aimi J, Barshop BA et al. (1992) A mutation in adenylosuccinate lyase associated with mental retardation and autistic features. Nat Genet 1:59 –63
16. Marie S, Cuppens H, Heuterspreute M et al. (1999) Mutation analysis in adenylosuccinate lyase deficiency. Eight novel mutations in the re-evaluated full ADSL coding sequence. Hum Mutat 13:197-202
17. Kmoch S, Hartmannova H, Stiburkova B et al. (2000) Human adenylosuccinate lyase (ADSL), cloning and characterization of full-length cDNA and its isoform, gene structure and molecular basis for ADSL deficiency in six patients. Hum Mol Genet 9:1501-1513
18. Marie S, Race V, Nassogne MC et al. (2002) Mutation of a nuclear respiratory factor 2 binding site in the 5‘untranslated region of the ADSL gene in three patients with adenylosuccinate lyase deficiency. Am J Hum Genet 71:14-21
19. Laikind PK, Seegmiller JE, Gruber HE (1986) Detection of 5’- phosphoribosyl-4-(N-succinylcarboxamide)-5-aminoimidazole in urine by use of the Bratton-Marshall reaction: identification of patients deficient in adenylosuccinate lyase activity. Anal Biochem 156:81-90
20. Ito T, Kuilenburg v ABP, Bootsma AH et al. (2000) Rapid screening of high-risk patients for disorders of purine and pyrimidine metabolism using HPLC-electrospray tandem mass spectrometry of liquid urine or urine-soaked filter paper strips. Clin Chem 46:445-452
21. Hartmann S, Okun JG, Schmidt C et al. (2006) Comprehensive detection of disorders of purine and pyrimidine metabolism by HPLC with electrospray ionization tandem mass spectrometry. Clin Chem 52:1127-1137
22. Marie S, Flipsen JWAM, Duran M et al. (2000) Prenatal diagnosis in adenylosuccinate lyase deficiency. Prenat Diagn 20:33-36
23. Jureccka A, Tylki-Szymanska A, Zikanova M et al. (2008) d-Ribose therapy in four Polish patients with adenylosuccinate lyase deficiency: absence of positive effect. J Inherit Metab Dis 31:548
24. Marie S, Heron B, Bitoun P et al. (2004) AICA-Ribosiduria: a novel, neurologically devastating inborn error of purine biosynthesis caused by mutation of ATIC. Am J Hum Genet 74:1276-1281
25. Fishbein WN, Armbrustmacher VW, Griffin JL (1978) Myoadenylate deaminase deficiency: a new disease of muscle. Science 200:545-548
26. Shumate JB, Katnik R, Ruiz M et al. (1979) Myoadenylate deaminase deficiency. Muscle Nerve 2:213-216
27. Mercelis R, Martin JJ, de Barsy T, Berghe v d G (1987) Myoadenylate deaminase deficiency: absence of correlation with exercise intolerance in 452 muscle biopsies. J Neurol 234:385-389
28. Berghe v d G, Bontemps F, Vincent MF, Bergh v d F (1992) The purine nucleotide cycle and its molecular defects. Prog Neurobiol 39:547-561
29. Vockley J, Rinaldo P, Bennett MJ et al. (2000) Synergistic heterozygosity: disease resulting from multiple partial defects in one or more metabolic pathways. Mol Genet Metab 71:10-18
30. Hers HG, Berghe v d G (1979) Enzyme defect in primary gout. Lancet 1:585-586
31. Ogasawara N, Goto H, Yamada Y et al. (1987) Deficiency of AMP deaminase in erythrocytes. Hum Genet 75:15-18
32. Morisaki T, Gross M, Morisaki H et al. (1992) Molecular basis of AMP deaminase deficiency in skeletal muscle. Proc Natl Acad Sci USA 89:6457-6461
33. Safranow K, Czyzycka E, Binczak-Kuleta A et al. (2009) Association of C34T AMPD1 gene polymorphism with features of metabolic syndrome in patients with coronary artery disease or heart failure. Scand J Clin Lab Invest 69:102-112
34. Sabina RL, Fishbein WN, Pezeshkpour G et al. (1992) Molecular analysis of the myoadenylate deaminase deficiencies. Neurology 42:170-179
35. Zollner N, Reiter S, Gross M et al. (1986) Myoadenylate deaminase deficiency: successful symptomatic therapy by high dose oral administration of ribose. Klin Wochenschr 64:1281-1290
36. Pannicke U, Honig M, Hess, I (2009) Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2. Nat Genet 41:101-105
37. Lagresle-Peyrou C, Six EM, Picard C et al. (2009) Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness. Nat Genet 41:106-111
38. Hershfield MS, Arredondo-Vega FX, Santisteban I (1997) Clinical expression, genetics and therapy of adenosine deaminase (ADA) deficiency. J Inherit Metab Dis 20:179-185
39. Hershfield M (2009) Adenosine deaminase deficiency. In: Pagon RA, Bird TD, Dolan CR, Stephens K (eds) GeneReviews [Internet]. Seattle (WA) University of Washington, Seattle; 1993-2006 Oct 03 [updated 2009 Jul 14]
40. Bollinger ME, Arredondo-Vega FX, Santisteban I et al. (1996): Hepatic dysfunction as a complication of adenosine deaminase deficiency (brief report). N Engl J Med 334:1367-1371
41. Hirschhorn R, Yang DR, Puck JM et al. (1996) Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency. Nat Genet 13:290-295
42. Gaspar HB, Aiuti A, Porta F et al. (2009) How I treat ADA deficiency. Blood 114:3524-3532
43. Hershfield MS (1995) PEG-ADA replacement therapy for adenosine deaminase deficiency: an update after 8.5 years. Clin Immunol Immunopathol 76:S228-S232
44. Booth C, Gaspar HB (2009) Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID). Biologics Targets Ther 3:349-358
45. Blaese RM, Culver KW, Miller AD et al. (1995) T-Lymphocytedirected gene therapy for ADA-SCID: initial trial results after 4 years. Science 270:475-480
46. Aiuti A, Cattaneo F, Galimberti S et al. (2009) Gene therapy for immunodeficiency due to adenosine deaminase deficiency N Engl J Med 360:447-458
47. Cavazzana-Calvo M, Lagresle C, Hacein-Bey-Abina S, Fisher A (2005) Gene therapy for severe combined immunodeficiency. Annu Rev Med 56:585-602
48. Kohn DB (2010) Update on gene therapy for immune deficiencies. Clin Immunol 135:247-254
49. Valentine WN, Paglia DE, Tartaglia AP, Gilsanz F (1977) Hereditary hemolytic anemia with increased red cell adenosine deaminase (45- to 70-fold) and decreased adenosine triphosphate. Science 195:783-785
50. Willig TN, Perignon JL, Gustavsson P et al. (1998) High adenosine deaminase level among healthy probands of Diamond Blackfan anemia (DBF) cosegregates with the DBA gene region on chromosome 19q13. Blood 92:4422-4427
51. Markert ML (1991) Purine nucleoside phosphorylase deficiency. Immunodefic Rev 3:45-81
52. Markert ML, Finkel BD, McLaughlin TM et al. (1997) Mutations in purine nucleoside phosphorylase deficiency. Hum Mutat 9:118-121
53. Carpenter PA, Ziegler JB, Vowels MR (1996) Late diagnosis and correction of purine nucleoside phosphorylase deficiency with allogeneic bone marrow transplantation. Bone Marrow Transplant 17:121-124
54. Baguette C, Vermylen C, Brichard B et al. (2002) Persistent developmental delay despite successful bone marrow transplantation for purine nucleoside phosphorylase deficiency. J Pediatr Hematol Oncol 24:69-71
55. Delicou S, Kitra-Roussou V, Peristeri J (2007) Successful HLA-identical hematopoietic stem cell transplantation in a patient with purine nucleoside phosphorylase deficiency. Pediatr Transplant 11:799-803
56. Wadman SK, Duran M, Beemer FA et al. (1983) Absence of hepatic molybdenum cofactor: an inborn error of metabolism leading to a combined deficiency of sulphite oxidase and xanthine dehydrogenase. J Inherit Metab Dis 6 [Suppl 1]:78-83
57. Shih VE, Abroms IF, Johnson JL et al. (1977) Sulfite oxidase deficiency. Biochemical and clinical investigations of a hereditary metabolic disorder in sulfur metabolism. N Engl J Med 297:1022-1028
58. Mendel RR, Bittner F (2006) Cell biology of molybdenum. Biochim Biophys Acta 1763:621-635
59. Ichida K, Amaya Y, Kamatani N et al. (1997) Identification of two mutations in human xanthine dehydrogenase gene responsible for classical type I xanthinuria. J Clin Invest 99:2391-2397
60. Yamamoto T, Moriwaki Y, Takahashi S et al. (2003) Identification of a new point mutation in the human molybdenum cofactor sulferase gene that is responsible for xanthinuria type II. Metabolism 52:1501-1504
61. Reiss J, Johnson JL (2003) Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH. Hum Mutat 21:569-576
62. Arenas M, Fairbanks LD, Vijayakumar K et al. (2009) An unusual genetic variant in the MOCS1 gene leads to complete missplicing of an alternatively spliced exon in a patient with molybdenum cofactor deficiency. J Inherit Metab Dis 32:560-569
63. Veldman A, Santamaria-Araujo JA, Sollazzo S et al. (2010) Successful treatment of molybdenum cofactor deficiency type A with pCMP. Pediatrics 125:1249-1254
64. Lesch M, Nyhan WL (1964) A familial disorder of uric acid metabolism and central nervous system dysfuntion. Am J Med 36:561-570
65. Jinnah HA, Visser JE, Harris JC et al. (2006) Delineation of the motor disorder of Lesch-Nyhan disease. Brain 129:1201-1217
66. Kelley WN, Greene ML, Rosenbloom FM et al. (1969) Hypoxanthine- guanine phosphoribosyltransferase deficiency in gout. Ann Intern Med 70:155-206
67. Jinnah HA, Ceballos-Picot I, Torres RJ et al. (2010) Attenuated variants of Lesch-Nyhan disease. (Lesch-Nyhan Disease International Study Group) Brain 133:671-689
68. Ernst M, Zametkin AJ, Matochik JA et al. (1996) Presynaptic dopaminergic deficits in Lesch-Nyhan disease. N Engl J Med 334:1568-1572
69. Guibinga GH, Hsu S, Friedmann T (2010) Deficiency of the housekeeping gene hypoxanthine-guanine phosphoribosyltransferase (HPRT) dysregulates neurogenesis. Mol Ther 18:54-62
70. Nyhan WL, O’Neill JP, Harris JC, Jinnah HA (2009) Lesch-Nyhan syndrome. In: Pagon RA, Bird TD, Dolan CR, Stephens K eds GeneReviews [Internet]. University of Washington, Seattle; 1993- 2000 Sep 25 [updated 2010 Jun 10]
71. Jinnah HA, De Gregorio L, Harris JC et al. (2000) The spectrum of inherited mutations causing HPRT deficiency: 75 new cases and a review of 196 previously reported cases. Mutat Res 463:309-326
72. Alford RL, Redman JB, O’Brien WE, Caskey CT (1995) Lesch-Nyhan syndrome: carrier and prenatal diagnosis. Prenat Diagn 15:329-338
73. Kaufman JM, Greene ML, Seegmiller JE (1968) Urine uric acid to creatinine ratio – a screening test for inherited disorders of purine metabolism. Phosphoribosyl-transferase (PRT) deficiency in Xlinked cerebral palsy and in a variant of gout. J Pediatr 73:583-592
74. Seegmiller JE, Rosenbloom FM, Kelley WN (1967) Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science 155:1682-1684
75. Page T, Bakay B, Nissinen E, Nyhan WL (1981) Hypoxanthine-guanine phosphoribosyltransferase variants: correlation of clinical phenotype with enzyme activity. J Inherit Metab Dis 4:203-206
76. Watts RWE, McKeran RO, Brown E et al. (1974) Clinical and biochemical studies on treatment of Lesch-Nyhan syndrome. Arch Dis Child 49:693-702
77. Nyhan WL, Parkman R, Page T et al. (1986) Bone marrow transplantation in Lesch-Nyhan disease. Adv Exp Med Biol 195A:167-170
78. Taira T, Kobayashi T, Hori T (2003) Disappearance of self-mutilating behavior in a patient with Lesch-Nyhan syndrome after bilateral chronic stimulation of the globus pallidus internus (case report). J Neurosurg 98:414-416
79. Acker v KJ, Simmonds HA, Potter C, Cameron JS (1977) Complete deficiency of adenine phosphoribosyltransferase. Report of a family. N Engl J Med 297:127-132
80. Bollee G, Dollinger C, Boutaud L et al. (2010) Phenotype and genotype characterization of adenine phosphoribosyltransferase deficiency. J Am Soc Nephrol 21:679-688
81. Greenwood MC, Dillon MJ, Simmonds HA et al. (1982) Renal failure due to 2,8-dihydroxyadenine urolithiasis. Eur J Pediatr 138:346-349
82. Hidaka Y, Tarle SA, Fujimori S et al. (1988) Human adenine phosphoribosyltransferase deficiency. Demonstration of a single mutant allele common to the Japanese. J Clin Invest 81:945-950
83. Sahota A, Chen J, Stambrook PJ, Tischfield JA (1991) Mutational basis of adenine phosphoribosyltransferase deficiency. Adv Exp Med Biol 309B:73-76
84. Eller P, Rosenkranz AR, Mark W et al. (2004) Four consecutive renal transplantations in a patient with adenine phosphoribosyltransferase deficiency. Clin Nephrol 61:217-221
85. Scaglia F, Dimmock D, Wong LJ (2009) DGUOK-related mitochondrial DNA depletion syndrome, hepatocerebral form. Pagon RA, Bird TD, Dolan CR, Stephens K e(ds) GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2009 Jun 18
86. Mandel H, Szargel R, Labay V et al. (2001) The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Nat Genet 29:337-341
87. Dimmock DP, Dunn JK, Feigenbaum A et al. (2008) Abnormal neurological features predict poor survival and should preclude liver transplantation in patients with deoxyguanosine kinase deficiency. Liver Transplant 14:1480-1485
88. Bulst S, Abicht A, Holinksi-Feder E et al. (2009) In vitro supplementation with dAMP/dGMP leads to partial restoration of mtDNA levels in mitochondrial depletion syndr omes. Hum Mol Genet 18:1590-1599
89. Aarbakke J, Janka-Schaub G, Elion GB (1997) Thiopurine biology and pharmacology. Trends Pharmacol Sci 18:3-7
90. Sahasranaman S, Howard D, Roy S (2008) Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol 64:753-767
91. Yates CR, Krynetski EY, Loennechen T et al. (1997) Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med 126:608-614
92. Sanderson J, Ansari A, Marinaki T, Duley J (2004) Thiopurine methyltransferase: should it be measured before commencing thiopurine drug therapy? Ann Clin Biochem 41:294-302
93. Huguley CM, Bain JA, Rivers SL, Scoggins RB (1959) Refractory megaloblastic anemia associated with excretion of orotic acid. Blood 14:615-634
94. Smith LH (1973) Pyrimidine metabolism in man. N Engl J Med 288:764-771
95. Bailey CJ (2009) Orotic aciduria and uridine monophosphate synthase: a reappraisal short report. J Inherit Metab Dis 27 June (Epub ahead of print; DOI 10.1007/s10545-009-1176-y; PMID: 19562503 [PubMed – as supplied by publisher])
96. Perry ME, Jones ME (1989) Orotic aciduria fibroblasts express a labile form of UMP synthase. J Biol Chem 264:15522-15528
97. Suchi M, Mizuno H, Kawai Y et al. (1997) Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. Am J Hum Genet 60:525-539
98. Ng SB, Buckingham KJ, Lee C et al. (2010) Exome sequencing identifies the cause of a Mendelian disorder. Nat Genet 42:30-35
99. Gennip v AH, Abeling NGGM, Vreken P, Kuilenburg v ABP (1997) Inborn errors of pyrimidine degradation: clinical, biochemical and molecular aspects. J Inherit Metab Dis 20:203-213
100. Tuchman M, Stoeckeler JS, Kiang DT et al. (1985) Familial pyrimidinemia and pyrimidinuria associated with severe fluorouracil toxicity. N Engl J Med 313:245-249
101. Kuilenburg v ABP (2004) Dihydropyrimidine dehydrogenase and the efficacy and toxicity of 5-fluorouracil. Eur J Cancer 40:939-950
102. Kuilenburg v AB, Vreken P, Abeling NG et al. (1999) Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Hum Genet 104:1-9
103. Kuilenburg v ABP, Meijer J, Mul ANPM et al. (2009) Analysis of severely affected patients with dihydropyrimidine dehydrogenase deficiency reveals large intragenic rearrangements of DPYD and a de novo interstitial deletion del (1)(p13.3p21.3). Hum Genet 125:581-590
104. Kuilenburg v ABP, Meijer J, Mul ANPM (2010) Intragenic deletions and a deep intronic mutation affecting pre-mRNA splicing in the dihydropyrimidine gene as novel mechanisms causing 5-fluorouracil toxicity. Hum Genet 128:529-538
105. Gennip v AH, Driedijk PC, Elzinga A, Abeling NGGM (1992) Screening for defects of dihydropyrimidine degradation by analysis of amino acids in urine before and after acid hydrolysis. J Inherit Metab Dis 15:413-415
106. Kuilenburg v ABP, Dobritzsch D, Meijer J et al. (2010) Dihydropyrimidinase deficiency: phenotype, genotype and structural consequences in 17 patients. Biochim Biophys Acta 1802:639-648
107. Kuilenburg v AB, Meinsma R, Zonnenberg BA et al. (2003) Dihydropyrimidinase deficiency and severe 5-fluorouracil toxicity. Clin Cancer Res 9:4363-4367
108. Hamajima N, Kouwaki M, Vreken P et al. (1998) Dihydropyrimidinase deficiency: structural organization, chromosomal localization, and mutation analysis of the human dihydropyrimidinase gene. Am J Hum Genet 63:717-726
109. Putman CW, Rotteveel JJ, Wevers RA et al. (1997) Dihydropyrimidinase deficiency: a progressive neurological disorder? Neuropediatrics 28:106-110
110. Assmann B, Gohlich G, Baethman M et al. (2006a) Clinical findings and a therapeutic trial in the first patient with beta-ureidopropionase deficiency. Neuropediatrics 37:20-25
111. Kuilenburg v AB, Meinsma R, Beke E et al. (2004) Beta-ureidopropionase deficiency: an inborn error or pyrimidine degradation associated with neurological abnormalities. Hum Mol Genet 13:2793-2801
112. Yaplito-Lee J, Pitt J, Meiijer J et al. (2008) Beta-ureidopropionase deficiency presenting with congenital anomalies of the urogenital and colorectal systems. Mol Genet Metab 93:190-194
113. Assmann BE, Kuilenburg v AB, Distelmaier F et al. (2006b) Betaureidopopionase deficiency presenting with febrile status epilepticus. Epilepsia 47:215-217
114. Kuhara T, Ohse M, Inoue Y, Shinka T (2009) Five cases of s-ureidopropionase deficiency detected by GC/MS analysis of urine metabolome. J Mass Spectrom 44:214-221
115. Kolker S, Okun JG, Horster F et al. (2001) 3-Ureidopropionate contributes to the neuropathology of 3-ureidopropionase deficiency and severe propionic aciduria: a hypothesis. J Neurosci Res 66:666-673
116. Zanella A, Bianchi P, Fermo E, Valentini G (2006) Hereditary pyrimidine 5’-nucleotidase deficiency: from genetics to clinical manifestations. British J Haemat 133:113-123
117. Page T, Yu A, Fontanesi J, Nyhan WL (1997) Developmental disorder associated with increased cellular nucleotidase activity. Proc Natl Acad Sci USA 94:11601-11606
118. Nishino I, Spinazzola A, Papadimitriou A et al. (2000) MNGIE: an autosomal recessive disorder due to thymidine phosphorylase mutations. Ann Neurol 47:792-800
119. Halter J, Schupbach WM, Casali C et al. (2011) Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach. Bone Marrow Tranplant 2011 46:330-7
120. Ciccolini J, Dahan L, Andre N et al. (2010) Cytidine deaminase residual activity in serum is a predictive marker of early severe toxicities in adults after gemcitabine-based chemotherapies. J Clin Oncol 28:160-165
121. Revy P, Muto T, Levy Y et al. (2000) Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the hyper-IgM syndrome (HIGM2). Cell 102:565-575
122. Saada A, Shaag A, Mandel H et al. (2001) Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat Genet 29:342-344
123. Oskoui M, Davidzon G, Pascual J et al. (2006) Clinical spectrum of mitochondrial DNA depletion due to mutations in the thymidine kinase 2 gene. Arch Neurol 63:1122-1126
124. Lesko N, Naess K, Wibom R et al. (2010) Two novel mutations in thymidine kinase-2 cause early onset fatal encephalomyopathy and severe mtDNA depletion. Neuromuscul Disord 20:198-203