Heart changes may reveal late-onset Fabry disease, case report finds
Autopsy found enlargement beyond what known conditions could explain
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Careful examination of the heart’s structure raised suspicion of late-onset Fabry disease in a 72-year-old man whose heart abnormalities could not be fully explained by his existing health conditions, a case report describes.
The suspected diagnosis emerged only after the man died and an autopsy revealed a severely enlarged heart and severe left ventricular hypertrophy, or thickening of the muscular wall of the heart’s main pumping chamber. The extent of these changes appeared greater than expected from his long-standing high blood pressure and heart disease, prompting doctors to look for another cause.
Tissue analysis raises suspicion of Fabry disease
A closer examination of heart tissue under a microscope, including with conventional tissue stains, helped narrow the possible causes and revealed an accumulation of fatty material inside heart muscle cells. Together, the findings supported the suspected diagnosis of late-onset Fabry disease affecting the heart.
However, the diagnosis could not be confirmed because genetic, enzyme, and other specialized confirmatory tests were unavailable.
“This case highlights the importance of careful [heart structure] evaluation in the differential diagnosis of unexplained severe left ventricular hypertrophy and illustrates both the diagnostic utility and the limitations of conventional [microscopic tissue analysis] methods in autopsy practice,” the researchers wrote.
The study, “Cardiomegaly of Unknown Origin: Why Morphology Still Matters in the Genetic Era – A Case of Cardiac Fabry Disease,” was published in Medeniyet Medical Journal by a team of researchers at the Almazov National Medical Research Centre in St. Petersburg, Russia.
Fabry is caused by genetic mutations that result in a deficiency of alpha-galactosidase A, an enzyme needed to break down certain fatty molecules. As these substances accumulate within cells, they can cause organ damage and a wide range of Fabry symptoms.
The disease can vary widely. Classic Fabry generally begins in childhood or adolescence and affects multiple organs, whereas late-onset (or non-classic) Fabry typically develops after age 30 and may predominantly affect a single organ, most commonly the heart or kidneys.
When Fabry predominantly affects the heart, it can be difficult to recognize because the resulting heart muscle thickening can resemble that caused by more common conditions, including high blood pressure and hypertrophic cardiomyopathy. This overlap can delay a Fabry diagnosis.
Existing heart conditions complicated the diagnosis
The man had long-standing high blood pressure and type 2 diabetes, as well as ischemic heart disease, in which narrowed or blocked coronary arteries reduce blood flow to the heart.
He had a heart attack in 2016. Heart imaging at that time showed only moderate changes consistent with high blood pressure, without severe heart wall thickening.
In August 2025, however, he experienced another acute coronary event. An echocardiogram, or ultrasound of the heart, showed marked thickening of the left ventricle and reduced pumping ability. He subsequently underwent procedures to restore blood flow through narrowed coronary arteries.
In November 2025, the man was admitted to the researchers’ medical center for another planned heart procedure. After developing complications, he went into cardiac arrest six days later when blood clots blocked several major coronary arteries. Resuscitation was unsuccessful.
An autopsy confirmed severe coronary artery disease and a recent heart attack, but also revealed a severely enlarged heart weighing 911 g (about 2 pounds). The left ventricular wall was up to 2.4 cm (about 0.9 inches) thick.
Although high blood pressure and ischemic heart disease can enlarge the heart, the researchers considered these changes too severe to be fully explained by those conditions alone, prompting them to investigate other causes.
Microscopic changes point to a storage disorder
Under the microscope, heart muscle cells were markedly enlarged and contained numerous empty-looking spaces, creating a “lace-like” appearance that raised suspicion of a disease in which substances accumulate abnormally inside cells. Additional analyses helped narrow the possible causes, making hypertrophic cardiomyopathy less likely and ruling out some other conditions.
Because genetic testing and electron microscopy, a technique that provides highly detailed images of structures inside cells, were unavailable, the researchers stained frozen heart tissue with Sudan III, a dye used to reveal fats.
The stain showed orange-red deposits within heart muscle cells, indicating accumulation of fatty material and supporting the suspected diagnosis of late-onset Fabry disease.
However, Sudan III cannot identify the specific fatty substance that accumulates in Fabry, making the finding supportive rather than diagnostic. Without genetic or enzyme testing or electron microscopy, the researchers could not definitively confirm the diagnosis.
Despite these limitations, “this case emphasizes the continued importance of [heart structure] assessment in the diagnosis of rare [heart muscle diseases],” particularly after death, in resource-limited environments, or in cases involving genetic variants whose disease-causing role is uncertain, the researchers wrote. “[Fat] staining may serve as an adjunct to guide further diagnostic evaluation.”
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