Natural course of Fabry disease with the p. Arg227Ter (p.R227*) mutation in Finland: Fast study.
Adolescent
Adult
Aged
Aged, 80 and over
Brain
/ diagnostic imaging
Codon, Nonsense
Fabry Disease
/ genetics
Female
Finland
Genetic Association Studies
Genotype
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Phenotype
Severity of Illness Index
White People
/ genetics
Young Adult
alpha-Galactosidase
/ genetics
Fabry disease
cardiac hypertrophy
disease progression
gender
genotype
late-onset
phenotype
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
09
04
2019
revised:
06
07
2019
accepted:
23
07
2019
pubmed:
15
8
2019
medline:
23
6
2020
entrez:
15
8
2019
Statut:
ppublish
Résumé
Fabry disease is caused by a deficient or an absent alfa-galactosidase A activity and is an X-linked disorder that results in organ damage and a shortened life span, especially in males. The severity of the disease depends on the type of mutation, gender, skewed X-chromosome inactivation, and other still unknown factors. In this article, we describe the natural course of a common classic Fabry disease mutation, p.Arg227Ter or p.R227*, in Finland. Four males and ten females belonged to two extended families. The mean age was 46 years (SD 18.4). Six patients (43%) had cardiac hypertrophy, three patients (21%) had ischemic stroke, and none had severe kidney dysfunction. Three patients had atrial fibrillation; two patients who had atrial fibrillation also had pacemakers. All males over 30 years of age had at least one of the following manifestations: cardiac hypertrophy, stroke, or proteinuria. In females, the severity of Fabry disease varied from classic multiorgan disease to a condition that mimicked the attenuated cardiac variant. No one was totally asymptomatic without any signs of Fabry disease. Cardiac magnetic resonance imaging was performed on nine of 14 patients was the most sensitive for detecting early cardiac manifestations. Five patients (55%) had late gadolinium enhancement-positive segments. Cardiac involvement should be effectively detected in females before considering them asymptomatic mutation carriers.
Sections du résumé
BACKGROUND
Fabry disease is caused by a deficient or an absent alfa-galactosidase A activity and is an X-linked disorder that results in organ damage and a shortened life span, especially in males. The severity of the disease depends on the type of mutation, gender, skewed X-chromosome inactivation, and other still unknown factors.
METHODS
In this article, we describe the natural course of a common classic Fabry disease mutation, p.Arg227Ter or p.R227*, in Finland.
RESULTS
Four males and ten females belonged to two extended families. The mean age was 46 years (SD 18.4). Six patients (43%) had cardiac hypertrophy, three patients (21%) had ischemic stroke, and none had severe kidney dysfunction. Three patients had atrial fibrillation; two patients who had atrial fibrillation also had pacemakers. All males over 30 years of age had at least one of the following manifestations: cardiac hypertrophy, stroke, or proteinuria. In females, the severity of Fabry disease varied from classic multiorgan disease to a condition that mimicked the attenuated cardiac variant. No one was totally asymptomatic without any signs of Fabry disease. Cardiac magnetic resonance imaging was performed on nine of 14 patients was the most sensitive for detecting early cardiac manifestations. Five patients (55%) had late gadolinium enhancement-positive segments.
CONCLUSION
Cardiac involvement should be effectively detected in females before considering them asymptomatic mutation carriers.
Identifiants
pubmed: 31411008
doi: 10.1002/mgg3.930
pmc: PMC6785458
doi:
Substances chimiques
Codon, Nonsense
0
alpha-Galactosidase
EC 3.2.1.22
Banques de données
GENBANK
['NM_000169.2']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e00930Informations de copyright
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
Références
Circ Cardiovasc Genet. 2017 Oct;10(5):
pubmed: 29018006
J Med Genet. 2001 Nov;38(11):769-75
pubmed: 11732485
J Am Soc Nephrol. 2017 May;28(5):1631-1641
pubmed: 27979989
Pharmacol Ther. 2009 Apr;122(1):65-77
pubmed: 19318041
Pediatr Res. 2008 Nov;64(5):550-5
pubmed: 18596579
JACC Cardiovasc Imaging. 2011 Jun;4(6):592-601
pubmed: 21679893
PLoS One. 2018 Apr 5;13(4):e0193550
pubmed: 29621274
Mol Genet Genomic Med. 2019 Oct;7(10):e00930
pubmed: 31411008
J Med Genet. 2001 Nov;38(11):750-60
pubmed: 11694547
Gene. 2018 Jan 30;641:259-264
pubmed: 29079200
AJR Am J Roentgenol. 1987 Aug;149(2):351-6
pubmed: 3496763
J Cardiovasc Magn Reson. 2015 Feb 21;17:22
pubmed: 25890002
J Am Heart Assoc. 2016 May 31;5(6):
pubmed: 27247331
J Inherit Metab Dis. 2007 Apr;30(2):184-92
pubmed: 17347915
Am J Hum Genet. 1993 Dec;53(6):1186-97
pubmed: 7504405
Eur J Echocardiogr. 2008 Jul;9(4):438-48
pubmed: 18579482
Eur Heart J Cardiovasc Imaging. 2017 Sep 1;18(9):1034-1040
pubmed: 27590835
Orphanet J Rare Dis. 2015 Mar 27;10:36
pubmed: 25885911
PLoS One. 2016 Aug 25;11(8):e0161330
pubmed: 27560961
Genet Med. 2009 Nov;11(11):790-6
pubmed: 19745746
N Engl J Med. 1991 Feb 7;324(6):395-9
pubmed: 1846223
Orphanet J Rare Dis. 2016 Jun 29;11(1):88
pubmed: 27356758
Hum Genet. 2017 Jun;136(6):665-677
pubmed: 28349240
Int J Cardiol. 2008 Nov 28;130(3):367-73
pubmed: 18572264
PLoS One. 2014 Mar 13;9(3):e91757
pubmed: 24626231
Virchows Arch. 2008 Sep;453(3):291-300
pubmed: 18762974
J Clin Neurosci. 2015 Feb;22(2):423-5
pubmed: 25439755
N Engl J Med. 1995 Aug 3;333(5):288-93
pubmed: 7596372
J Cardiovasc Magn Reson. 2005;7(5):775-82
pubmed: 16353438
Mol Genet Metab Rep. 2018 Feb 06;15:43-45
pubmed: 30023289
Clin Genet. 2004 Apr;65(4):299-307
pubmed: 15025723
Mol Genet Metab. 2017 Sep;122(1-2):121-125
pubmed: 28847675
Mol Genet Metab. 2008 Feb;93(2):112-28
pubmed: 18037317
JIMD Rep. 2014;17:83-90
pubmed: 25224312