Biopsy of kidney may aid Fabry diagnosis, per case of woman, 55
Results can confirm or rule out disease when genetic testing is inconclusive
A kidney biopsy can be important in diagnosing Fabry disease because it can confirm or rule out the condition when other tests like genetic analysis are inconclusive, according to a report detailing the case of a middle-aged woman in Italy.
For this woman, 55, the results helped guide proper treatment, the researchers noted.
However, the team stressed that relying on a kidney biopsy can have both “diagnostic value and potential pitfalls.” In a second case described in their report, the researchers noted that, for a man of similar age, the findings of a kidney biopsy partially overlapped with those typical for Fabry disease. Other tests ultimately excluded its diagnosis for that patient, the team noted.
These two cases, the researchers wrote, illustrate kidney biopsy “as both a decisive tool and a potential source of diagnostic confusion.” But for individuals suspected of having Fabry disease, a biopsy can in fact play a key role in making a diagnosis, the team noted.
The study, “The importance of a multidisciplinary approach in two tricky cases: the perfect match for Fabry disease,” was published in BMC Nephrology.
Researchers warn that kidney biopsy results can be ‘confounding’
Fabry disease is caused by mutations in the GLA gene that result in a faulty alpha-galactosidase A (alpha-Gal A) enzyme in the body. Cells need this enzyme to break down a fatty molecule called globotriaosylceramide, or Gb3. Without it, Gb3 builds up to toxic levels, driving damage to tissues and organs.
Doctors typically diagnose Fabry disease by looking at symptoms and family history, alongside results of blood tests to check enzyme levels, and genetic testing. In cases in which kidney problems have no clear cause or genetic results are unclear, a kidney biopsy may help confirm the disease.
“Although genetic testing is widely available for the diagnosis of [Fabry disease], kidney biopsy remains a valuable tool, especially in complex genetic cases … that are not routinely included in standard diagnostic protocols,” the researchers wrote.
However, biopsy results are not always specific, which can make a diagnosis more challenging. Here, the researchers described “two cases that exemplify its pivotal role in confirming or excluding the suspected disease, proving to be both decisive and confounding in this complex clinical setting,” they wrote.
For man, 47, results suggesting Fabry were later discounted
The first case was that of the woman in her 50s, who had symptoms that were suggestive of Fabry affecting multiple organs in the body. An eye exam revealed cornea verticillata, a whorl-like pattern of golden brown or gray opacities in the eyes, which is common in Fabry. The woman also was experiencing tingling in her hands and had reduced sweating.
Blood tests showed low alpha-Gal A enzyme activity. However, genetic testing did not detect any disease-causing mutation in the GLA gene. Because she was adopted, her family history was unknown, but her 12-year-old son was later found to have signs of Fabry, supporting the diagnosis.
To further look for a diagnosis, a kidney biopsy was performed. Under a microscope, her kidney cells showed vacuoles and Zebra bodies, structures that form due to the accumulation of GB3, both hallmark findings of Fabry disease. Other findings included mild scarring and damaged blood vessels, despite normal protein levels in her urine.
These results confirmed a Fabry diagnosis, prompting further genetic testing on her skin cells, which finally identified a genetic mutation likely affecting the GLA gene’s activity. While the mutation was classified as uncertain in disease risk, doctors decided to start with enzyme replacement therapy (ERT), in which a version of the missing enzyme is supplied to ease symptoms.
This paper highlights the role of kidney biopsy in refining the diagnosis of [Fabry]. … The two cases presented here illustrate the role of kidney biopsy in resolving diagnostic challenges in [Fabry] and demonstrate its critical role when clinical and laboratory findings alone are insufficient for a definitive diagnosis.
The second case involved a 47-year-old man who was admitted to the hospital with high protein levels in his urine. He had early-stage chronic kidney disease but no family history of kidney problems or high blood pressure.
A kidney biopsy showed rare vacuoles in certain kidney cells, and electron microscopy revealed myeloid bodies — structures found within cells that are common in Fabry. However, these structures were smaller and differently distributed compared with the classic Zebra bodies seen in Fabry disease.
Additionally, there was no apparent buildup of Gb3. Further tests supported this finding: The man’s alpha-Gal A enzyme activity was normal, and genetic testing did not detect any disease-causing mutation. Further, the patient had no heart, skin, or eye symptoms.
Despite similarities to Fabry disease in the kidney biopsy, doctors excluded a Fabry diagnosis and started a treatment plan using medications to help prevent further damage to the kidneys.
“This paper highlights the role of kidney biopsy in refining the diagnosis of [Fabry],” the researchers wrote. “The two cases presented here illustrate the role of kidney biopsy in resolving diagnostic challenges in [Fabry] and demonstrate its critical role when clinical and laboratory findings alone are insufficient for a definitive diagnosis.”
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