Inborn errors of amino acid metabolism - from underlying pathophysiology to therapeutic advances.
Amino acids
Inborn errors of metabolism
Newborn screen
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
01 Nov 2023
01 Nov 2023
Historique:
received:
06
04
2023
accepted:
19
10
2023
medline:
24
11
2023
pubmed:
23
11
2023
entrez:
23
11
2023
Statut:
ppublish
Résumé
Amino acids are organic molecules that serve as basic substrates for protein synthesis and have additional key roles in a diverse array of cellular functions, including cell signaling, gene expression, energy production and molecular biosynthesis. Genetic defects in the synthesis, catabolism or transport of amino acids underlie a diverse class of diseases known as inborn errors of amino acid metabolism. Individually, these disorders are rare, but collectively, they represent an important group of potentially treatable disorders. In this Clinical Puzzle, we discuss the pathophysiology, clinical features and management of three disorders that showcase the diverse clinical presentations of disorders of amino acid metabolism: phenylketonuria, lysinuric protein intolerance and homocystinuria due to cystathionine β-synthase (CBS) deficiency. Understanding the biochemical perturbations caused by defects in amino acid metabolism will contribute to ongoing development of diagnostic and management strategies aimed at improving the morbidity and mortality associated with this diverse group of disorders.
Identifiants
pubmed: 37994477
pii: 335505
doi: 10.1242/dmm.050233
pmc: PMC10690057
pii:
doi:
Substances chimiques
Amino Acids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
Références
Mol Genet Metab. 2011;104 Suppl:S2-9
pubmed: 21937252
Mol Ther. 2020 Jan 8;28(1):304-312
pubmed: 31604675
Mol Genet Metab. 2018 Sep;125(1-2):86-95
pubmed: 30037505
Annu Rev Pathol. 2018 Jan 24;13:27-49
pubmed: 28934563
Am J Hum Genet. 2019 Apr 4;104(4):625-637
pubmed: 30879639
Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):2080-5
pubmed: 11742888
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2339-44
pubmed: 10051643
Free Radic Biol Med. 2002 May 1;32(9):906-11
pubmed: 11978492
Am J Physiol Cell Physiol. 2001 Oct;281(4):C1077-93
pubmed: 11546643
Expert Opin Drug Metab Toxicol. 2013 Sep;9(9):1207-18
pubmed: 23705856
J Pediatr. 2007 Jun;150(6):631-4, 634.e1
pubmed: 17517249
J Pediatr. 2010 Mar;156(3):427-32
pubmed: 19914636
J Inherit Metab Dis. 2003;26(2-3):259-65
pubmed: 12889665
J Clin Pathol. 2022 Sep 19;:
pubmed: 36123115
Front Pediatr. 2021 May 20;9:673957
pubmed: 34095032
Br J Pharmacol. 2023 Feb;180(3):264-278
pubmed: 36417581
Ann Neurol. 2017 Oct;82(4):640-646
pubmed: 28892570
Arch Dis Child. 1963 Oct;38:425-36
pubmed: 14065982
JIMD Rep. 2018;42:99-103
pubmed: 29380259
Am J Hum Genet. 2017 Feb 2;100(2):257-266
pubmed: 28132689
Mol Genet Metab. 2013 Jan;108(1):8-12
pubmed: 23266195
Amino Acids. 2007;32(4):561-72
pubmed: 17285228
J Inherit Metab Dis. 2021 May;44(3):677-692
pubmed: 33295057
J Inherit Metab Dis. 2005;28(2):123-9
pubmed: 15877200
J Inherit Metab Dis. 2015 Mar;38(2):257-63
pubmed: 25335805
Mol Genet Metab. 2020 May;130(1):36-40
pubmed: 32057642
Biochem J. 2017 May 25;474(12):1935-1963
pubmed: 28546457
Hum Mutat. 2002 Jun;19(6):641-55
pubmed: 12007221
Am J Physiol Cell Physiol. 2007 Jul;293(1):C191-8
pubmed: 17376816
J Hum Genet. 2019 Feb;64(2):67-71
pubmed: 30504912
Orphanet J Rare Dis. 2019 Mar 4;14(1):63
pubmed: 30832686
Mol Genet Metab. 2012 May;106(1):12-7
pubmed: 22402328
Science. 1964 Mar 27;143(3613):1443-5
pubmed: 14107447
Hum Mol Genet. 2020 Aug 3;29(13):2171-2184
pubmed: 32504080
Hum Mutat. 2004 Feb;23(2):206
pubmed: 14722927
Mol Genet Metab. 2022 Jun;136(2):111-117
pubmed: 35379539
Neuroreport. 2000 Apr 27;11(6):1361-4
pubmed: 10817622
Mol Genet Metab. 2022 Apr;135(4):327-332
pubmed: 35279366
Mol Ther Methods Clin Dev. 2020 Mar 13;17:568-580
pubmed: 32258219
J Biol Chem. 2004 Jul 16;279(29):29871-4
pubmed: 15087459
J Pediatr. 2004 Jun;144(6):830-2
pubmed: 15192637
Amino Acids. 2009 May;37(1):1-17
pubmed: 19301095
Mol Genet Metab Rep. 2022 May 14;32:100882
pubmed: 35600090
Pediatrics. 1963 Sep;32:338-43
pubmed: 14063511
Postgrad Med J. 1977 Aug;53(622):488-94; discussion 95-6
pubmed: 917963
Int Rev Cell Mol Biol. 2022;372:159-174
pubmed: 36064263
Am J Respir Crit Care Med. 1996 Feb;153(2):731-5
pubmed: 8564125
Genet Med. 2014 Feb;16(2):188-200
pubmed: 24385074
J Inherit Metab Dis. 2011 Feb;34(1):33-7
pubmed: 20567906
Int J Neonatal Screen. 2021 Jan 19;7(1):
pubmed: 33478143
J Glob Health. 2018 Dec;8(2):021102
pubmed: 30479748
Hum Mutat. 2008 Jan;29(1):14-21
pubmed: 17764084
N Engl J Med. 2004 May 13;350(20):2033-41
pubmed: 15141041
J Clin Invest. 2016 Jun 1;126(6):2372-84
pubmed: 27183385
Biochim Biophys Acta. 2002 Apr 24;1586(3):344-52
pubmed: 11997085
Am J Hum Genet. 1985 Jan;37(1):1-31
pubmed: 3872065
J Nutr. 2020 Sep 1;150(9):2239-2241
pubmed: 32652033
Chest. 1993 Oct;104(4):1176-82
pubmed: 8404187
Nat Genet. 1999 Mar;21(3):297-301
pubmed: 10080183
Eur J Hum Genet. 2020 Aug;28(8):1129-1134
pubmed: 32249831
J Inherit Metab Dis. 1996;19(5):627-34
pubmed: 8892019
J Inherit Metab Dis. 2013 Nov;36(6):923-8
pubmed: 23296368
Mol Genet Metab. 2018 May;124(1):27-38
pubmed: 29653686
Am J Med Genet C Semin Med Genet. 2011 Feb 15;157C(1):54-62
pubmed: 21308987
Mol Neurobiol. 2021 Jun;58(6):2897-2909
pubmed: 33550493
J Clin Invest. 1973 Oct;52(10):2571-8
pubmed: 4729050
Mol Genet Metab. 2018 Aug;124(4):223-229
pubmed: 29941359
Acta Paediatr Suppl. 1994 Dec;407:124-9
pubmed: 7766948
Int J Mol Sci. 2019 Oct 24;20(21):
pubmed: 31653080
Orphanet J Rare Dis. 2018 Jul 4;13(1):108
pubmed: 29973227
Mol Genet Metab. 2010 Jan;99(1):1-3
pubmed: 19819175
Orphanet J Rare Dis. 2017 Jan 5;12(1):3
pubmed: 28057010
Biochem Biophys Res Commun. 2002 Mar 15;291(5):1173-9
pubmed: 11883940
Mol Immunol. 2015 Oct;67(2 Pt B):416-25
pubmed: 26210182
Nat Rev Dis Primers. 2021 May 20;7(1):36
pubmed: 34017006
Mol Cell Biochem. 2010 Jun;339(1-2):1-7
pubmed: 20101519
Int J Neonatal Screen. 2021 Oct 25;7(4):
pubmed: 34842599
Hum Gene Ther. 2019 Oct;30(10):1274-1283
pubmed: 31364419
Eur J Pediatr. 2001 Aug;160(8):522-3
pubmed: 11548196
FASEB J. 1998 Oct;12(13):1319-29
pubmed: 9761775
Genes (Basel). 2020 Aug 29;11(9):
pubmed: 32872442
AJNR Am J Neuroradiol. 2005 Nov-Dec;26(10):2705-6
pubmed: 16286426
Acta Neuropathol. 1982;58(1):55-63
pubmed: 7136517
Neuroreport. 2002 Dec 20;13(18):2561-4
pubmed: 12499868
J Inherit Metab Dis. 2021 Nov;44(6):1382-1392
pubmed: 34528713
Am J Med Genet. 2002 Feb 15;108(1):57-63
pubmed: 11857551
Curr Opin Genet Dev. 2001 Jun;11(3):328-35
pubmed: 11377971
Lancet. 1965 Oct 23;2(7417):813-6
pubmed: 4158034
Metabolism. 2008 Apr;57(4):549-54
pubmed: 18328359
Curr Osteoporos Rep. 2018 Oct;16(5):554-560
pubmed: 30116976
Mol Genet Metab. 2010 Jul;100(3):229-33
pubmed: 20418136
Mol Genet Metab. 2010;99 Suppl 1:S59-63
pubmed: 20123472
Am J Med Genet A. 2021 Nov;185(11):3350-3358
pubmed: 34165242
J Clin Invest. 1996 Jul 15;98(2):285-9
pubmed: 8755636
Hum Mutat. 2002 Aug;20(2):117-26
pubmed: 12124992
Mol Genet Metab. 2012 Apr;105(4):585-9
pubmed: 22325938
Mol Genet Metab. 2011;104 Suppl:S73-9
pubmed: 21821452
Mol Genet Metab. 2007 Aug;91(4):335-42
pubmed: 17540596
Biochim Biophys Acta. 1996 Apr 12;1315(3):159-62
pubmed: 8611653
J Pediatr. 1981 Jul;99(1):159-60
pubmed: 7252655
Biochimie. 2020 Jun;173:48-56
pubmed: 31857119
Cell Rep. 2018 Aug 28;24(9):2520
pubmed: 30157442
Eur J Hum Genet. 2005 May;13(5):628-34
pubmed: 15756301
Nat Med. 2018 Oct;24(10):1519-1525
pubmed: 30297904
Mol Genet Metab. 2016 Mar;117(3):351-4
pubmed: 26689745
Mol Genet Metab. 2020 Aug;130(4):239-246
pubmed: 32593547
Eur J Pediatr. 2000 Oct;159 Suppl 2:S102-6
pubmed: 11043154
Pediatrics. 2013 Jun;131(6):e1881-8
pubmed: 23690520
Eur J Pediatr. 1998 Apr;157 Suppl 2:S84-7
pubmed: 9587032
Gene. 2014 Jan 25;534(2):197-203
pubmed: 24211323
N Engl J Med. 1974 Sep 12;291(11):537-43
pubmed: 4212055
Am J Hum Genet. 2000 Jan;66(1):92-9
pubmed: 10631139
J Inherit Metab Dis. 2006 Oct;29(5):688-9
pubmed: 16972179
Mol Genet Metab. 2012 Mar;105(3):408-15
pubmed: 22221392
Eur J Pediatr. 1998 Feb;157(2):130-1
pubmed: 9504787
Nat Chem Biol. 2012 Aug;8(8):701-6
pubmed: 22706200
JIMD Rep. 2020 Jan 08;52(1):3-10
pubmed: 32154053
Am J Hum Genet. 2020 Aug 6;107(2):234-250
pubmed: 32668217
J Pediatr. 2004 Apr;144(4):545-8
pubmed: 15069409
J Inherit Metab Dis. 2001 Aug;24(4):437-47
pubmed: 11596648
Hum Mutat. 1999;13(5):362-75
pubmed: 10338090
J Hum Genet. 2019 Sep;64(9):849-858
pubmed: 31213652
Hum Mol Genet. 2000 Feb 12;9(3):431-8
pubmed: 10655553
J Inherit Metab Dis. 2002 Sep;25(5):333-46
pubmed: 12408183
Transl Pediatr. 2014 Apr;3(2):49-62
pubmed: 26835324
Mol Pharm. 2022 Dec 5;19(12):4625-4630
pubmed: 35862031
J Inherit Metab Dis. 2017 Jan;40(1):49-74
pubmed: 27778219
Genet Test. 2003 Spring;7(1):29-35
pubmed: 12820699
J AAPOS. 2001 Oct;5(5):311-5
pubmed: 11641642
Transl Sci Rare Dis. 2020 Aug 03;5(1-2):81-86
pubmed: 33134088
Neurology. 2003 Jan 28;60(2):275-9
pubmed: 12552044