Undiagnosed Fabry disease in cardiac changes, renal impairment

A prolonged clinical history of cardiac changes, including valvular disease, without an apparent cause and accompanied by impaired renal function may be a sign of nondiagnosis. Fabry diseaseproposes a case report.

the report, “Transcatheter tricuspid valve replacement for Anderson-Fabry disease with severe tricuspid regurgitation“in Issue.

Fabry disease, as well as Anderson-Fabry disease, is it causes by mutations in GLA The gene, which contains instructions for making an enzyme called alpha-galactosidase A (alpha-gal A).

A deficiency or deficiency of alpha-gal A activity leads to the accumulation of certain lipid molecules—particularly globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3)—through several organs, including the kidneys, brain, heart, eyes, and skin.

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

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A history of heart and kidney disease

Researchers at China’s Naval Military Medical University described the case of a 54-year-old man who was hospitalized with swollen legs and flatulence, symptoms that had lasted for more than a year, but had worsened in the past three months. .

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

Upon admission, his blood pressure and heart rate were normal. A diastolic murmur—a “wheeze”—was heard when the heart muscle relaxed between beats, possibly due to valve regurgitation.

Laboratory work revealed signs of impaired renal function, as evidenced by elevated creatinine levels and decreased glomerular filtration rate, which assesses how well the kidneys are filtering.

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

Lessons learned from this case is that Constellation Progressive is gratuitous [left ventricle] Wall thickness or LV hypertrophy [enlargement]valvular abnormalities, and multi-organ involvement should lead to a differential diagnosis of [Fabry disease].

A transthoracic echocardiogram (TTE), a noninvasive imaging test of the heart, showed that the walls of the ventricles and 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 is beating.

At the age of 48, the man developed tricuspid reflux. He was not eligible for a second open-chest surgery, but had an 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 on follow-up cardiac examination. The man’s symptoms abated, the swelling in his legs disappeared, and he had only mild shortness of breath after exertion.

Diagnosis of Fabry disease

At a one-year follow-up visit, he reported fatigue and shortness of breath after physical activity, which was relieved by rest.

Cardiac examinations showed that the size of the left atrium was twice as large as in previous examinations. The wall thickness of the right ventricle remained constant, while the diameter of the interventricular septum—the space between both ventricles—and the diameter of the posterior wall were thicker than before surgery.

These findings led the researchers to suspect Fabry disease.

“Our patient had many of the hallmarks of AFD [Anderson Fabry disease] Including gradually increasing the low voltage [left ventricle] and RV [right ventricle] wall thickness, which was initially but incorrectly assumed to result from aging and renal dysfunction, the researchers wrote.

Genetic testing confirmed the mutation GLA gene. He also had elevated levels of lyso-Gb3.

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

Laboratory work confirmed a decrease in lyso-Gb3 levels and an improvement in renal function, as evidenced by a decrease in creatinine levels and an increase in glomerular filtration rate. Also, cardiac imaging parameters have improved, supporting the positive effects of ERT outside of renal function.

Lessons learned from this case is that the progressive LV constellation is unexplained [left ventricle] Wall thickness or LV hypertrophy [enlargement]valvular abnormalities, and multi-organ involvement should lead to a differential diagnosis of [Fabry disease]the researchers wrote.

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