GLA Gene Mutation in Hypertrophic Cardiomyopathy with a New Variant Description: Is it Fabry's Disease?
Abstract Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the alpha galactosidase A gene (GLA) that lead to the enzymatic deficiency of alpha galactosidase (α-Gal A), resulting in the accumulation of globotriaosylceramide (Gb3) and globotriaosylsphing...
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| Language: | English |
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Sociedade Brasileira de Cardiologia (SBC)
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| Series: | Arquivos Brasileiros de Cardiologia |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2019000700077&lng=en&tlng=en |
| _version_ | 1818179866878541824 |
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| author | Ândrea Virgínia Chaves-Markman Manuel Markman Eveline Barros Calado Ricardo Flores Pires Marcelo Antônio Oliveira Santos-Veloso Catarina Maria Fonseca Pereira Andréa Bezerra de Melo da Silveira Lordsleem Sandro Gonçalves de Lima Brivaldo Markman Filho Dinaldo Cavalcanti de Oliveira |
| author_facet | Ândrea Virgínia Chaves-Markman Manuel Markman Eveline Barros Calado Ricardo Flores Pires Marcelo Antônio Oliveira Santos-Veloso Catarina Maria Fonseca Pereira Andréa Bezerra de Melo da Silveira Lordsleem Sandro Gonçalves de Lima Brivaldo Markman Filho Dinaldo Cavalcanti de Oliveira |
| author_sort | Ândrea Virgínia Chaves-Markman |
| collection | DOAJ |
| description | Abstract Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the alpha galactosidase A gene (GLA) that lead to the enzymatic deficiency of alpha galactosidase (α-Gal A), resulting in the accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3), causing multiple organ dysfunctions. Objective: To perform GLA gene screening in a group of patients with echocardiographic diagnosis of hypertrophic cardiomyopathy (HCM). Methods: a cross-sectional study was conducted with HCM patients from a university hospital. Patients with coronary artery disease and valvulopathies were excluded. Mutation analysis of the GLA gene was performed. In male subjects, the analysis was performed after evidence of low α-Gal A activity. Results: 60 patients with echocardiographic diagnosis of HCM were included. Age ranged from 12 to 85 years and 60% were women. Mean myocardial fibrosis percentage on MRI was 10.7 ± 13.1% and mean ventricular thickness was18.7 ± 6.7 mm. Four patients had the following GLA gene mutations: c.967C>A (p.Pro323Thr), not yet described in the literature; c.937G>T (p.Asp313Tyr); and c.352C>T (p.Arg118Cys). All patients had normal levels of lyso-Gb3 and non-ischemic myocardial fibrosis on magnetic resonance imaging; one patient had proteinuria and one patient had ventricular tachycardia. Conclusion: in this study, the frequency of mutation in the GLA gene in patients with HCM was 6.7%. A novel mutation in exon 6 of the GLA gene, c.967C>A (p.Pro323Thr), was identified. Patients with HCM may have GLA mutations and FD should be ruled out. Plasma (lyso-Gb3) levels do not seem to be sufficient to attain a diagnosis and organ biopsy should be considered. |
| first_indexed | 2024-12-11T21:10:41Z |
| format | Article |
| id | doaj.art-19dd875b8b704f26929f46b56ded93da |
| institution | Directory Open Access Journal |
| issn | 1678-4170 |
| language | English |
| last_indexed | 2024-12-11T21:10:41Z |
| publisher | Sociedade Brasileira de Cardiologia (SBC) |
| record_format | Article |
| series | Arquivos Brasileiros de Cardiologia |
| spelling | doaj.art-19dd875b8b704f26929f46b56ded93da2022-12-22T00:50:43ZengSociedade Brasileira de Cardiologia (SBC)Arquivos Brasileiros de Cardiologia1678-41701131778410.5935/abc.20190112S0066-782X2019000700077GLA Gene Mutation in Hypertrophic Cardiomyopathy with a New Variant Description: Is it Fabry's Disease?Ândrea Virgínia Chaves-MarkmanManuel MarkmanEveline Barros CaladoRicardo Flores PiresMarcelo Antônio Oliveira Santos-VelosoCatarina Maria Fonseca PereiraAndréa Bezerra de Melo da Silveira LordsleemSandro Gonçalves de LimaBrivaldo Markman FilhoDinaldo Cavalcanti de OliveiraAbstract Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the alpha galactosidase A gene (GLA) that lead to the enzymatic deficiency of alpha galactosidase (α-Gal A), resulting in the accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3), causing multiple organ dysfunctions. Objective: To perform GLA gene screening in a group of patients with echocardiographic diagnosis of hypertrophic cardiomyopathy (HCM). Methods: a cross-sectional study was conducted with HCM patients from a university hospital. Patients with coronary artery disease and valvulopathies were excluded. Mutation analysis of the GLA gene was performed. In male subjects, the analysis was performed after evidence of low α-Gal A activity. Results: 60 patients with echocardiographic diagnosis of HCM were included. Age ranged from 12 to 85 years and 60% were women. Mean myocardial fibrosis percentage on MRI was 10.7 ± 13.1% and mean ventricular thickness was18.7 ± 6.7 mm. Four patients had the following GLA gene mutations: c.967C>A (p.Pro323Thr), not yet described in the literature; c.937G>T (p.Asp313Tyr); and c.352C>T (p.Arg118Cys). All patients had normal levels of lyso-Gb3 and non-ischemic myocardial fibrosis on magnetic resonance imaging; one patient had proteinuria and one patient had ventricular tachycardia. Conclusion: in this study, the frequency of mutation in the GLA gene in patients with HCM was 6.7%. A novel mutation in exon 6 of the GLA gene, c.967C>A (p.Pro323Thr), was identified. Patients with HCM may have GLA mutations and FD should be ruled out. Plasma (lyso-Gb3) levels do not seem to be sufficient to attain a diagnosis and organ biopsy should be considered.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2019000700077&lng=en&tlng=enFabry Disease/geneticCardiomyopathy, HypertrophicHypertrophy, Left VentricularGlycosphingolipids |
| spellingShingle | Ândrea Virgínia Chaves-Markman Manuel Markman Eveline Barros Calado Ricardo Flores Pires Marcelo Antônio Oliveira Santos-Veloso Catarina Maria Fonseca Pereira Andréa Bezerra de Melo da Silveira Lordsleem Sandro Gonçalves de Lima Brivaldo Markman Filho Dinaldo Cavalcanti de Oliveira GLA Gene Mutation in Hypertrophic Cardiomyopathy with a New Variant Description: Is it Fabry's Disease? Arquivos Brasileiros de Cardiologia Fabry Disease/genetic Cardiomyopathy, Hypertrophic Hypertrophy, Left Ventricular Glycosphingolipids |
| title | GLA Gene Mutation in Hypertrophic Cardiomyopathy with a New Variant Description: Is it Fabry's Disease? |
| title_full | GLA Gene Mutation in Hypertrophic Cardiomyopathy with a New Variant Description: Is it Fabry's Disease? |
| title_fullStr | GLA Gene Mutation in Hypertrophic Cardiomyopathy with a New Variant Description: Is it Fabry's Disease? |
| title_full_unstemmed | GLA Gene Mutation in Hypertrophic Cardiomyopathy with a New Variant Description: Is it Fabry's Disease? |
| title_short | GLA Gene Mutation in Hypertrophic Cardiomyopathy with a New Variant Description: Is it Fabry's Disease? |
| title_sort | gla gene mutation in hypertrophic cardiomyopathy with a new variant description is it fabry s disease |
| topic | Fabry Disease/genetic Cardiomyopathy, Hypertrophic Hypertrophy, Left Ventricular Glycosphingolipids |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2019000700077&lng=en&tlng=en |
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