Fabry disease in cardiology practice: Literature review and expert point of view

Hagège, Albert; Réant, Patricia; Habib, Gilbert; Damy, Thibaud; Barone-Rochette, Gilles; Soulat, Gilles; Donal, Erwan; Germain, Dominique P.

doi:10.1016/j.acvd.2019.01.002

Cited by 78 publications

(86 citation statements)

References 51 publications

(74 reference statements)

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“…According to Human Gene Mutation Database, over 900 mutations GLA have been reported worldwide. GLA mutations result in functionally deficient GLA enzyme, which leads to progressive accumulation of glycosphingolipid substrates, particularly globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) in different organs 1. In the late-onset form of FD, which is more common than the classic type, patients have residual enzyme activity.…”

Section: Introductionmentioning

confidence: 99%

“…In the late-onset form of FD, which is more common than the classic type, patients have residual enzyme activity. Cardiomyopathy is often the predominant or the only manifestation of the late-onset disease, and typically develops in the middle age in hemizygous and heterozygous subjects 1. Cardiovascular complications are the major cause of death in FD 2.…”

Section: Introductionmentioning

confidence: 99%

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Cardiomyopathy associated with the Ala143Thr variant of the α-galactosidase A gene

Valtola

Nino-Quintero

Hedman

et al. 2020

Heart

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ObjectiveTo investigate whether the Ala143Thr variant of the α-galactosidase A gene (A143T/GLA), with conflicting interpretations of pathogenicity, is associated with Fabry cardiomyopathy.MethodsThe index patient, a woman in her 60s with cardiomyopathy, was screened for variants in 59 cardiomyopathy-related genes. A143T/GLA, the only rare variant found, was screened in 10 relatives. GLA activity and lyso-Gb3 levels were measured and echocardiography was performed in 8 of 9 subjects carrying A143T/GLA. Cardiac magnetic resonance (CMR) imaging and 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT) were performed in four adult A143T/GLA carriers. Endomyocardial biopsy was obtained from two adult A143T/GLA carrying sons of the index patient.ResultsThe index patient and her elder son had a pacemaker implantation because of sick sinus syndrome and atrioventricular block. GLA activities were decreased to 25%–40% of normal in both sons and one granddaughter. Lyso-Gb3 levels were elevated in both sons. In CMR, the index patient and her two sons had left ventricular (LV) hypertrophy and/or dilatation. The elder son had late gadolinium enhancement, high CMR-derived T1 time and positive FDG signal in PET/CT in the basal inferolateral LV wall. The younger son had low T1 time and the mother had positive FDG signal in PET/CT in the basal inferolateral LV wall. Endomyocardial biopsy of both sons showed myocardial accumulation compatible with glycolipids in light and electron microscopy, staining with anti-Gb3 antibody available for the younger son. Five female relatives with A143T/GLA had no cardiomyopathy in cardiac imaging.ConclusionsA143T/GLA is likely a late-onset Fabry cardiomyopathy causing variant with incomplete penetrance.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cardiomyopathy associated with the Ala143Thr variant of the α-galactosidase A gene

Valtola

Nino-Quintero

Hedman

et al. 2020

Heart

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“…4 Pain represents the most striking symptom in children with FD, but overall quality of life (QoL) is often considerably impacted and characterised by fatigue, anxiety, depression, and school absences. Symptomatic organ complications typically emerge in young adult patients, including chronic kidney disease (CKD) progression to renal failure and left ventricular hypertrophy (LVH) associated with myocardial fibrosis and arrhythmias, 7 pulmonary involvement, 8 sudden deafness 9 transient ischemic attacks, strokes, and eventually premature death. 6 FD can manifest with a range of severities and has a spectrum of phenotypes.…”

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confidence: 99%

Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients

Germain¹,

Fouilhoux²,

Decramer

et al. 2019

Clinical Genetics

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107

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Fabry disease (FD), a rare X-linked disease, can be treated with bi-monthly infusion of enzyme replacement therapy (ERT) to replace deficient α-galactosidase A (AGAL-A). ERT reduces symptoms, improves quality of life (QoL), and improves clinical signs and biochemical markers. ERT initiation in childhood could slow or stop progressive organ damage. Preventative treatment of FD from childhood is thought to avoid organ damage in later life, prompting a French expert working group to collaborate and produce recommendations for treating and monitoring children with FD. Organ involvement should be assessed by age 5 for asymptomatic boys (age 12-15 for asymptomatic girls), and immediately for children diagnosed via symptoms. The renal, cardiac, nervous and gastrointestinal systems should be assessed, as well as bone, skin, eyes, hearing, and QoL. The plasma biomarker globotriaosylsphingosine is also useful. ERT should be considered for symptomatic boys and girls with neuropathic pain, pathological albuminuria (≥3 mg/mmol creatinine), severe GI involvement and abdominal pain or cardiac involvement. ERT should be considered for asymptomatic boys from the age of 7. Organ involvement should be treated as needed. Early diagnosis and management of FD represents a promising strategy to reduce organ damage, morbidity and premature mortality in adulthood.

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“…It is known that males are affected more frequently and more seriously because of the X-linked inheritance in Fabry disease. However, it has been reported that heterozygous women are also affected by the disease, but the disease symptoms such as left ventricular hypertrophy appear later in life (about 10 years later) (3,4). Myocardial fibrosis, which is a guide in determining the prognosis of Fabry disease and the patients who will benefit from enzyme replacement therapy, has been reported in women without left ventricular hypertrophy, unlike men (3,5).…”

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confidence: 99%

“…The fact that left ventricular hypertrophy has been reported in only one out of every three women diagnosed with Fabry disease in the literature supports this idea. (3)(4)(5). The study by Barman et al (1) is valuable for being the first study to investigate the incidence of Fabry disease in patients with unexplained left ventricular hypertrophy in Turkey.…”

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confidence: 99%

Are Female Patients More Overlooked in the Diagnosis of Fabry Disease?

Gürdoğan¹,

Akkuş²

2019

Balkan Med J

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To the Editor, We have read the article by Barman et al. (1) titled, "The Prevalence of Fabry disease Among Turkish Patients with non-obstructive Hypertrophic Cardiomyopathy: Insights from a Screening Study" with interest. In their descriptive study, the researchers found that the frequency of Fabry disease was 2.5% by screening 80 patients (53 males) diagnosed with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction. The authors emphasized that Fabry disease should be kept in mind in the differential diagnosis of patients with unexplained left ventricular hypertrophy (1). Fabry disease is an X-linked recessive lysosomal storage disorder, first described in 1898, characterized by a deficiency of α-galactosidase A resulting from a genetic mutation. In Fabry disease, glycosphingolipid accumulation occurs in many tissues, especially in the nervous system, heart, kidneys, and skin (2,3).

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Fabry disease in cardiology practice: Literature review and expert point of view

Cited by 78 publications

References 51 publications

Cardiomyopathy associated with the Ala143Thr variant of the α-galactosidase A gene

Cardiomyopathy associated with the Ala143Thr variant of the α-galactosidase A gene

Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients

Are Female Patients More Overlooked in the Diagnosis of Fabry Disease?

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