title: Adenylosuccinate lyase deficiency.
abstract: Adenylosuccinate lyase ADSL) deficiency is a defect of purine metabolism affecting purinosome assembly and reducing metabolite fluxes through purine de novo synthesis and purine nucleotide recycling pathways. Biochemically this defect manifests by the presence in the biologic fluids of two dephosphorylated substrates of ADSL enzyme: succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado). More than 80 individuals with ADSL deficiency have been identified, but incidence of the disease remains unknown. The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The fatal neonatal form has onset from birth and presents with fatal neonatal encephalopathy with a lack of spontaneous movement, respiratory failure, and intractable seizures resulting in early death within the first weeks of life. Patients with type I (severe form) present with a purely neurologic clinical picture characterized by severe psychomotor retardation, microcephaly, early onset of seizures, and autistic features. A more slowly progressing form has also been described (type II, moderate or mild form), as having later onset, usually within the first years of life, slight to moderate psychomotor retardation and transient contact disturbances. Diagnosis is facilitated by demonstration of SAICAr and S-Ado in extracellular fluids such as plasma, cerebrospinal fluid and/or followed by genomic and/or cDNA sequencing and characterization of mutant proteins. Over 50 ADSL mutations have been identified and their effects on protein biogenesis, structural stability and activity as well as on purinosome assembly were characterized. To date there is no specific and effective therapy for ADSL deficiency.
authors.affiliation: Department of Genetics, University of Gdańsk, ul. Wita Stwosza 59, 80-308, Gdańsk, Poland, ajurecka@gmail.com.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jurecka
authors.forename: Marie
authors.initials: M
authors.lastname: Zikanova
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kmoch
authors.forename: Anna
authors.initials: A
authors.lastname: Tylki-Szymańska
mesh_terms: D000264:Adenylosuccinate Lyase / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001321:Autistic Disorder / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D003937:Diagnosis, Differential; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D012307:Risk Factors
chemical_list: D000264:Adenylosuccinate Lyase
references.citation: Prenat Diagn. 2000 Jan;20(1):33-6
references.pmid: 10701848
references.citation: Cytogenet Cell Genet. 1987;44(2-3):142-7
references.pmid: 3568763
references.citation: Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):12872-6
references.pmid: 20615962
references.citation: Adv Exp Med Biol. 1986;195 Pt A:27-33
references.pmid: 3014834
references.citation: Clin Chem. 1995 May;41(5):744-51
references.pmid: 7729054
references.citation: J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S159-62
references.pmid: 20177786
references.citation: Prog Neurobiol. 1992 Nov;39(5):547-61
references.pmid: 1529104
references.citation: Hum Mutat. 2010 Apr;31(4):445-55
references.pmid: 20127976
references.citation: Clin Chim Acta. 2007 Feb;376(1-2):184-9
references.pmid: 17010959
references.citation: Lancet. 1989 Jan 21;1(8630):158-9
references.pmid: 2563072
references.citation: Pediatr Neurol. 2010 Nov;43(5):351-4
references.pmid: 20933180
references.citation: J Inherit Metab Dis. 1997 Jun;20(2):193-202
references.pmid: 9211192
references.citation: Electrophoresis. 1995 Oct;16(10):1927-9
references.pmid: 8586067
references.citation: FEBS Lett. 1996 Mar 11;382(1-2):43-7
references.pmid: 8612761
references.citation: J Inherit Metab Dis. 1992;15(3):416-8
references.pmid: 1405483
references.citation: Clin Chim Acta. 1986 May 15;156(3):279-87
references.pmid: 3719985
references.citation: Eur J Paediatr Neurol. 1999;3(1):3-6
references.pmid: 10727185
references.citation: J Inherit Metab Dis. 2000 Jun;23(4):434-7
references.pmid: 10896312
references.citation: Adv Exp Med Biol. 1986;195 Pt A:21-5
references.pmid: 3728154
references.citation: Neuropediatrics. 2014 Feb;45(1):50-5
references.pmid: 23504561
references.citation: Eur J Hum Genet. 2009 Jan;17(1):133-6
references.pmid: 18830228
references.citation: J Inherit Metab Dis. 2008 Dec;31 Suppl 2:S329-32
references.pmid: 18649008
references.citation: Eur J Paediatr Neurol. 2012 Jul;16(4):343-8
references.pmid: 21903433
references.citation: Trends Neurosci. 2008 Jun;31(6):273-8
references.pmid: 18471903
references.citation: Am J Hum Genet. 2002 Jul;71(1):14-21
references.pmid: 12016589
references.citation: Lancet. 1984 Nov 10;2(8411):1058-61
references.pmid: 6150139
references.citation: J Am Acad Child Adolesc Psychiatry. 2000 Mar;39(3):274-5
references.pmid: 10714045
references.citation: Hum Mutat. 1999;13(3):197-202
references.pmid: 10090474
references.citation: Am J Med Genet A. 2003 Jul 15;120A(2):185-90
references.pmid: 12833398
references.citation: Eur J Pediatr. 2012 Jan;171(1):131-8
references.pmid: 21625931
references.citation: J Child Neurol. 2012 May;27(5):645-9
references.pmid: 22140128
references.citation: Hum Mol Genet. 2012 Apr 1;21(7):1534-43
references.pmid: 22180458
references.citation: J Inherit Metab Dis. 1997 Jul;20(3):343-4
references.pmid: 9266351
references.citation: Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1231-3
references.pmid: 15571235
references.citation: J Clin Invest. 1980 Dec;66(6):1419-23
references.pmid: 7440723
references.citation: J Inherit Metab Dis. 1995;18(5):602-8
references.pmid: 8598641
references.citation: Pediatrics. 2000 Apr;105(4):E46
references.pmid: 10742367
references.citation: Annu Rev Nutr. 2007;27:415-30
references.pmid: 17444813
references.citation: J Biol Chem. 2012 Oct 19;287(43):36201-7
references.pmid: 22955281
references.citation: J Inherit Metab Dis. 1995;18(3):291-4
references.pmid: 7474894
references.citation: J Child Neurol. 2001 May;16(5):301-8
references.pmid: 11392513
references.citation: Mol Genet Metab. 2011 Jan;102(1):61-8
references.pmid: 20884265
references.citation: Mol Genet Metab. 2006 Sep-Oct;89(1-2):19-31
references.pmid: 16839792
references.citation: Front Genet. 2011 Jun 20;2:36
references.pmid: 22303332
references.citation: Science. 2008 Apr 4;320(5872):103-6
references.pmid: 18388293
references.citation: J Med Genet. 2002 Jun;39(6):440-2
references.pmid: 12070256
references.citation: Brain Dev. 2000 Sep;22(6):383-6
references.pmid: 11042421
references.citation: J Chromatogr B Biomed Sci Appl. 1999 Apr 16;726(1-2):53-8
references.pmid: 10348170
references.citation: J Biol Chem. 2010 Apr 9;285(15):11093-9
references.pmid: 20157113
references.citation: Neuropediatrics. 2002 Aug;33(4):186-9
references.pmid: 12368987
references.citation: Adv Exp Med Biol. 1998;431:177-80
references.pmid: 9598054
references.citation: Adv Exp Med Biol. 1998;431:185-9
references.pmid: 9598056
references.citation: Biochemistry. 2009 Jun 16;48(23):5291-302
references.pmid: 19405474
references.citation: Hum Mol Genet. 2000 Sep 1;9(14):2159-65
references.pmid: 10958654
references.citation: Neuropediatrics. 1998 Feb;29(1):51-3
references.pmid: 9553952
references.citation: Eur J Pediatr. 1988 Nov;148(2):126-31
references.pmid: 3234432
references.citation: J Inherit Metab Dis. 1993;16(2):415-24
references.pmid: 8412002
references.citation: Adv Exp Med Biol. 2000;486:75-8
references.pmid: 11783531
references.citation: Adv Exp Med Biol. 1994;370:367-70
references.pmid: 7660930
references.citation: Anal Biochem. 1986 Jul;156(1):81-90
references.pmid: 3740420
references.citation: Mol Genet Metab. 2008 Aug;94(4):435-42
references.pmid: 18524658
references.citation: NMR Biomed. 2010 Jun;23(5):441-5
references.pmid: 20175147
references.citation: J Biol Chem. 1975 Aug 25;250(16):6304-14
references.pmid: 169235
references.citation: Clin Chem. 2006 Jun;52(6):1127-37
references.pmid: 16613999
references.citation: Pediatr Neurol. 1997 Apr;16(3):252-5
references.pmid: 9165520
references.citation: Eur J Biochem. 1980 Sep;110(2):371-7
references.pmid: 7439166
references.citation: J Inherit Metab Dis. 1993;16(2):425-34
references.pmid: 8412003
references.citation: Brain Dev. 2007 Oct;29(9):600-2
references.pmid: 17485188
references.citation: Dev Med Child Neurol. 2013 Nov;55(11):1060-4
references.pmid: 23937257
references.citation: Biochim Biophys Acta. 2013 Aug;1834(8):1545-53
references.pmid: 23714113
references.citation: J Pediatr. 2007 Jan;150(1):57-61.e2
references.pmid: 17188615
references.citation: Nat Genet. 1992 Apr;1(1):59-63
references.pmid: 1302001
references.citation: Hum Mol Genet. 2000 Jun 12;9(10):1501-13
references.pmid: 10888601
references.citation: Clin Biochem. 2013 Dec;46(18):1899-901
references.pmid: 24183879
references.citation: Cytogenet Cell Genet. 1993;64(3-4):201-3
references.pmid: 8404037
references.citation: Lancet. 1989 Mar 4;1(8636):500
references.pmid: 2563871