Cardiac Involvement in Fabry Disease and the Role of Multimodality Imaging in Diagnosis and Disease Monitoring

Umer, Muhammad; Motwani, Manish; Jefferies, John L.

doi:10.1016/j.cpcardiol.2022.101439

Cited by 6 publications

(16 citation statements)

References 104 publications

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“…The deficiency of α-GAL activity impairs globotriaosylceramide (GL3) metabolism, leading to the progressive accumulation of GL3 and lyso-GL3 (globotriaosylsphingosine) in various organs, especially the heart, kidneys, and the cerebrovascular system [ 7 ]. Thurberg et al [ 8 ] demonstrated that GL3 is deposited as dense, beaded cytoplasmic inclusions within the interstitial capillary endothelial cells and cardiomyocytes on the endomyocardial biopsies.…”

Section: Pathophysiologymentioning

confidence: 99%

“…Extra-cardiac red flags during the 1st and 2nd decades of life include cornea verticillata, angiokeratomas, hypohidrosis, recurrent diarrhea, and abdominal and neuropathic pain. Hearing loss, tinnitus, vertigo, cryptogenic stroke, and renal dysfunction are common in the 3rd and 4th decades of life [ 7 ]. A comprehensive diagnostic approach is needed for early diagnosis, including the early recognition of clinical red flags, and appropriate genetic and/or enzymatic testing and imaging tests depending on the organ system involved.…”

Section: Diagnostic Evaluationmentioning

confidence: 99%

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Treatment of Fabry Disease: Established and Emerging Therapies

Umer

2023

Pharmaceuticals

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Fabry disease (FD) is a rare, X-linked inherited disorder of glycosphingolipid metabolism. It leads to the progressive accumulation of globotriaosylceramide within lysosomes due to a deficiency of α-galactosidase A enzyme. It involves multiple organs, predominantly the renal, cardiac, and cerebrovascular systems. Early diagnosis and treatment are critical to prevent progression to irreversible tissue damage and organ failure, and to halt life-threatening complications that can significantly reduce life expectancy. This review will focus on the established and emerging treatment options for FD.

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Section: Pathophysiologymentioning

confidence: 99%

Section: Diagnostic Evaluationmentioning

confidence: 99%

Treatment of Fabry Disease: Established and Emerging Therapies

Umer

2023

Pharmaceuticals

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“…Multiparametric CMR has a vital role in differentiating FD cardiomyopathy from other etiologies of LVH and can strongly impact clinical decision-making and prognosis by initiating disease-specific therapies ( 46 ) ( Table 1 ). Cardiac and renal disease may not manifest clinically until adolescence or adulthood.…”

Section: Differentiation Of Hypertrophic Myocardium Patient Selection...mentioning

confidence: 99%

“…Early diagnosis is vital to prevent cardiac involvement and stop disease progression to avoid life-threatening complications of arrhythmias, myocardial infarction, and heart failure. The efficacy of treatment decreases with advancing stages of cardiomyopathy ( 2 ), thus worsening the overall prognosis. Orsborne et al ( 82 ) developed a prognostic model based on age, native myocardial T 1 dispersion, and left ventricular mass index (LVMi) to provide an accurate estimate of the 5-year risk of adverse cardiac outcomes.…”

Section: Prognosismentioning

confidence: 99%

“…More than 1000 GLA gene variants have been identified–including pathogenic mutations, variants of unknown significance, and benign polymorphisms. The deficiency of α-GAL activity impairs the breakdown of the glycosphingolipid, globotriaosylceramide (GL3)–resulting in progressive accumulation throughout the body, including the blood vessels, heart, kidneys, skin, nervous system, gastrointestinal system, and eyes ( 2 ). The massive accumulation of GL3 in cardiomyocytes is detectable as early as childhood and adolescence ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

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Cardiac MRI in Fabry disease

Umer

Kalra²

2023

Front. Cardiovasc. Med.

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Fabry disease is a rare, progressive X-linked inherited disorder of glycosphingolipid metabolism due to a deficiency of α-galactosidase A enzyme. It leads to the accumulation of globotriaosylceramide within lysosomes of multiple organs, predominantly the vascular, renal, cardiac, and nervous systems. Fabry cardiomyopathy is characterized by increased left ventricular wall thickness/mass, functional abnormalities, valvular heart disease, arrhythmias, and heart failure. Early diagnosis and treatment are critical to avoid cardiac or renal complications that can significantly reduce life expectancy in untreated FD. This review will focus on the role of cardiovascular magnetic resonance imaging in the diagnosis, clinical decision-making, and monitoring of treatment efficacy.

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Renal and multisystem effectiveness of 3.9 years of migalastat in a global real‐world cohort: Results from the followME Fabry Pathfinders registry

Hughes,

Sunder‐Plassmann,

Jovanovic

et al. 2024

J of Inher Metab Disea

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Fabry disease is a progressive, X‐linked lysosomal disorder caused by reduced or absent α‐galactosidase A activity due to GLA variants. The effects of migalastat were examined in a cohort of 125 Fabry patients with migalastat‐amenable GLA variants in the followME Pathfinders registry (EUPAS20599), an ongoing, prospective, patient‐focused registry evaluating outcomes for current Fabry disease treatments. We report annualised estimated glomerular filtration rate (eGFR) and Fabry‐associated clinical events (FACEs) in a cohort of patients who had received ≥3 years of migalastat treatment in a real‐world setting. As of August 2022, 125 patients (60% male) had a mean migalastat exposure of 3.9 years. At enrolment, median age was 58 years (males, 57; females, 60) with a mean eGFR of 83.7 mL/min/1.73 m2 (n = 122; males, 83.7; females, 83.8) and a median left ventricular mass index of 115.1 g/m2 (n = 61; males, 131.2; females, 98.0). Mean (95% confidence interval) eGFR annualised rate of change in the overall cohort (n = 116) was −0.9 (−10.8, 9.9) mL/min/1.73 m2/year with a similar rate of change observed across patients with varying levels of kidney function at enrolment. Despite population age and baseline morbidity, 80% of patients did not experience a FACE during the mean 3.9 years of migalastat exposure. The incidence of renal, cardiac, and cerebrovascular events was 2.0, 83.2, and 4.1 events per 1000 patient‐years, respectively. These data support a role of migalastat in preserving renal function and multisystem effectiveness during ≥3 years of migalastat treatment in this real‐world Fabry population.

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Cardiac Involvement in Fabry Disease and the Role of Multimodality Imaging in Diagnosis and Disease Monitoring

Cited by 6 publications

References 104 publications

Treatment of Fabry Disease: Established and Emerging Therapies

Treatment of Fabry Disease: Established and Emerging Therapies

Cardiac MRI in Fabry disease

Renal and multisystem effectiveness of 3.9 years of migalastat in a global real‐world cohort: Results from the followME Fabry Pathfinders registry

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