Fabry disease caused by the GLA p.Phe113Leu (p.F113L) variant: Natural history in males

Oliveira, João Paulo; Nowak, Albina; Barbey, Frédéric; Torres, Márcia Regina Simas Gonçalves; Nunes, José Pedro L.; Teixeira-e-Costa, Fernando; Carvalho, Fernanda; Sampaio, Susana; Tavares, Isabel; Pereira, Odete; Soares, Ana Luiza Gonçalves; Carmona, Cátia; Cardoso, Maria Teresa; Jurca-Simina, Iulia E.; Spada, Marco; Ferreira, Susana; Germain, Dominique P.

doi:10.1016/j.ejmg.2019.103703

Cited by 23 publications

(33 citation statements)

References 43 publications

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“…Fabry disease affects all ethnicities, with some geographical clusters based on founder mutations 39–41 . The reported prevalence of FD varies according to the screening method employed.…”

Section: Epidemiologymentioning

confidence: 99%

“…This so‐called ‘cardiac variant’ has slower progression due to residual AGAL‐A enzyme activity and less vascular endothelial Gb 3 accumulation 41,64 . However, the cardiac variant may occasionally present with some degree of extra‐cardiac involvement including stroke and renal dysfunction, but the attribution of such complications to FD should be made with caution, and a kidney biopsy should be considered for differential diagnosis in all cases exhibiting albuminuria/proteinuria with deteriorating renal function, particularly in patients with concurrent risk factors for chronic kidney disease 40,65 …”

Section: Diagnosis Of Fabry Diseasementioning

confidence: 99%

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An expert consensus document on the management of cardiovascular manifestations of Fabry disease

Linhart

Germain

Olivotto

et al. 2020

European J of Heart Fail

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148

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Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants in the-galactosidase A (GLA) gene that leads to reduced or undetectable-galactosidase A enzyme activity and progressive accumulation of globotriaosylceramide and its deacylated form globotriaosylsphingosine in cells throughout the body. FD can be multisystemic with neurological, renal, cutaneous and cardiac involvement or be limited to the heart. Cardiac involvement is characterized by progressive cardiac hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death. The cardiac management of FD requires specific measures including enzyme replacement therapy or small pharmacological chaperones in patients carrying amenable pathogenic GLA gene variants and more general management of cardiac symptoms and complications. In this paper, we summarize current knowledge of FD-related heart disease and expert consensus recommendations for its management.

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Section: Epidemiologymentioning

confidence: 99%

Section: Diagnosis Of Fabry Diseasementioning

confidence: 99%

An expert consensus document on the management of cardiovascular manifestations of Fabry disease

Linhart

Germain

Olivotto

et al. 2020

European J of Heart Fail

Self Cite

148

119

View full text Add to dashboard Cite

show abstract

“…We found eight patients with the p.F113L variant, which has been associated in literature with the late-onset form of FD, with severe cardiac involvement particularly in homozygosis [ 35 , 36 ]. The risk of clinically relevant kidney and cerebral involvement is not clear because, in most cases, the mutation presents with an incomplete α-galactosidase deficiency [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Screening for Fabry Disease in Kidney Transplant Recipients: Experience of a Multidisciplinary Team

et al. 2020

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Fabry disease (FD) is a rare cause of end-stage renal disease requiring kidney transplantation. Data on the incidence of unrecognized FD in kidney transplant recipients are scarce and probably underestimated. This study evaluated the incidence of FD in a population of kidney recipients, with a particular focus of the multidisciplinary approach for an early clinical assessment and therapeutic approach. Two hundred sixty-five kidney transplant recipients were screened with a genetic analysis for α-galactosidase A (GLA) mutation, with measurement of α-Gal A enzyme activity and Lyso Gb3 levels. Screening was also extended to relatives of affected patients. Seven patients (2.6%) had a GLA mutation. Two patients had a classic form of FD with Fabry nephropathy. Among the relatives, 15 subjects had a GLA mutation, and two had a Fabry nephropathy. The clinical and diagnostic assessment was completed after a median of 3.2 months, and mean time from diagnosis to treatment was 4.6 months. This study reported a high incidence of unrecognized GLA mutations in kidney transplant recipients. Evaluation and management by a multidisciplinary team allowed for an early diagnosis and treatment, and this would result in a delay in the progression of the disease and, finally, in better long-term outcomes.

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“…All of these findings were highly suggestive of AFD cardiomyopathy, for which an enzymatic and genetic study was carried out, revealing a low alpha galactosidase (α-Gal A) protein concentration (<2.8 ng/mL, the lowest quantification limit detected; normal range >15.3 ng/mL) and increased lyso-GB3 levels. Moreover, the genetic study was positive for heterozygosis mutation NM_000169.2: c.337T>C; p.Phe113Leu in the GLA gene (p.F113L), a pathogenic mutation associated with late-onset AFD and severe cardiac involvement [ 4 ].…”

Section: Case Reportmentioning

confidence: 99%

Different Phenotypes of Anderson-Fabry Disease Identified with Cardiac Magnetic Resonance Imaging in a Family with the Same Late-Onset Mutation

et al. 2020

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Case series Patients: Male, 60-year-old • Male, 58-year-old • Female, 28-year-old Final Diagnosis: Late-onset Anderson Fabry disease Symptoms: Left ventricular hypertrophy Medication: — Clinical Procedure: Cardiac magnetic resonance imaging Specialty: Cardiology Objective: Unusual clinical course Background: Cardiac magnetic resonance imaging (CMR) is the only noninvasive test capable of differentiating between hypertrophic cardiomyopathy (HCM) and late-onset Anderson-Fabry disease (AFD). The purpose of this report is to show how CMR led to diagnosis of AFD in 3 family members, 1 of whom previously was misdiagnosed with HCM, and how late-onset AFD can present with different cardiac phenotypes, even in a family with the same pathogenic mutation. Case Report: A 60-year-old man was referred because of evidence of left ventricular hypertrophy (LVH) on an electrocardiogram (ECG) that was performed to screen for cardiomyopathy. One of his siblings previously had been diagnosed with HCM and atrial fibrillation. The patient’s ECG and echocardiographic findings were suspicious for HCM. CMR showed severe symmetrical LVH but tissue characterization sequences were highly suggestive of AFD cardiomyopathy. Enzymatic and genetic testing confirmed the diagnosis of late-onset AFD (presence of the GLA p.F113.L mutation). The brother of the index patient then was re-evaluated and also diagnosed with late-onset AFD. He was found to have the same pathogenic mutation but with a presentation of asymmetrical septal LVH. The daughter of the index patient was positive for the same mutation but did not have LVH. Conclusions: The fact that patients with late-onset AFD can present with different LVH and fibrosis patterns, even in the presence of the same pathogenic mutation, underscores the importance of including AFD in the differential diagnosis of HCM. CMR is fundamental for differentiating between those 2 entities and defining the pathological phase of AFD. A correct diagnosis can have a substantial impact on patient management, and more so on thier families.

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Fabry disease caused by the GLA p.Phe113Leu (p.F113L) variant: Natural history in males

Cited by 23 publications

References 43 publications

An expert consensus document on the management of cardiovascular manifestations of Fabry disease

An expert consensus document on the management of cardiovascular manifestations of Fabry disease

Screening for Fabry Disease in Kidney Transplant Recipients: Experience of a Multidisciplinary Team

Different Phenotypes of Anderson-Fabry Disease Identified with Cardiac Magnetic Resonance Imaging in a Family with the Same Late-Onset Mutation

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