Undiagnosed Fabry disease in heart changes, kidney failure

A long clinical history of cardiac alterations, including heart valve disorders, with no apparent cause and accompanied by renal dysfunction may be indicative of an undiagnosed disease. Fabry diseasesuggests a case report.

The report, “Transcatheter tricuspid valve replacement for Anderson Fabry disease with severe tricuspid regurgitationwas published in CASE.

Fabry disease, also called Anderson Fabry disease, is cause by mutations in GLA gene, which contains instructions for making an enzyme called alpha-galactosidase A (alpha-gal A).

The lack or insufficient activity of alpha-gal A leads to the accumulation of certain fatty molecules – in particular globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) – in several organs, including the kidneys, the brain , heart, eyes and skin.

Heart disease is common with Fabry disease. In fact, one feature is the enlargement and excessive thickness of the heart’s lower left pumping chamber (left ventricle). However, severe tricuspid regurgitation, in which the valve between the two right chambers of the heart does not close properly, causing blood to leak backwards, is rare in Fabry disease.

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A history of heart and kidney problems

Researchers from the Naval Military Medical University of China described the case of a 54-year-old man who was hospitalized with swelling in both legs and abdominal distension, symptoms that had lasted for more than a year, but have worsened over the past three months. .

His clinical history included pacemaker surgery at age 39, as well as a kidney transplant and mitral valve replacement. The mitral valve regulates the passage of blood from the upper left chamber of the heart (left atrium) to the left ventricle. He had no family history of cardiovascular or kidney disease.

On admission, he had normal blood pressure and heart rate. A diastolic murmur – a “whoosh” when the heart muscle relaxes between beats – was heard, possibly due to valve regurgitation.

Lab work revealed signs of poor kidney function, as shown by high creatinine levels and low glomerular filtration rate, which gauges how well the kidneys filter.

He also had levels of heart failure markers, including N-terminal b-type natriuretic peptide precursor (NT-proBNP) and B-type natriuretic peptide (BNP).

The lessons of this case are that the constellation of unexplained progressive disorders [left ventricle] LV wall thickness or hypertrophy [enlargement]valvular abnormalities and multiorgan involvement should trigger the differential diagnosis of [Fabry disease].

A transthoracic echocardiogram (TTE), a noninvasive cardiac imaging test, showed that the walls of both ventricles and the two upper chambers (atria) were unusually thick.

The systolic pressure in his pulmonary artery was slightly elevated and his mitral valve was functioning normally. Systolic pressure is the pressure that blood exerts on the arteries when the heart beats.

At 48, the man developed severe tricuspid regurgitation. He was not eligible for a second open-chest surgery, but for interventional tricuspid valve surgery, a minimally invasive procedure to replace the tricuspid valve.

No obvious valve regurgitation or leakage was observed after surgery, and the new valve functioned normally, as shown by follow-up cardiac analysis. The man’s symptoms subsided, the swelling in both legs was gone and he only had mild shortness of breath after exertion.

Diagnosing Fabry disease

During a one-year follow-up visit, he reported fatigue and shortness of breath after physical activity, which improved with rest.

Cardiac scans showed that the volume of the left atrium was twice as large as in previous scans. Right ventricular wall thickness remained stable, while interventricular septal diameter – the space between the two ventricles – and posterior wall diameter were thicker than before surgery.

These findings led researchers to suspect Fabry disease.

“Our patient had many features of AFD [Anderson Fabry disease] of which LV gradually increased [left ventricle] and VR [right ventricle] wall thickness, which was initially, but incorrectly, presumed to be due to aging and kidney dysfunction,” the researchers wrote.

Genetic testing has confirmed a mutation in the GLA embarrassed. He also had high levels of lyso-Gb3.

The patient started treatment with Fabrazyme, an enzyme replacement therapy (ERT) approved to treat Fabry disease, in January 2022 (45 mg, four times daily). Her fatigue, asthma, leg swelling and shortness of breath improved after treatment.

Laboratory work confirmed a drop in lyso-Gb3 levels and improvements in kidney function, as evidenced by decreased creatinine levels and an increase in glomerular filtration rate. Additionally, his cardiac imaging parameters improved, supporting the positive effects of ERT beyond kidney function.

“The lessons of this case are that the constellation of unexplained progressive LVs [left ventricle] LV wall thickness or hypertrophy [enlargement]valvular abnormalities and multiorgan involvement should trigger the differential diagnosis of [Fabry disease]“, wrote the researchers.

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