Woman, 32, with many symptoms gets Fabry disease diagnosis
Case report showcases importance of considering disease in females
A wide array of symptoms that affected the kidneys and cardiovascular and nervous systems led to a diagnosis of Fabry disease for a 32-year-old woman, a study in India shows.
Given that Fabry has been historically considered a male disease and that women carrying a Fabry-causing mutation may not develop the disease, the case “underscores the importance of maintaining a high index of suspicion for Fabry disease, even in female patients,” wrote the researchers, who said the case also emphasizes “the need for a comprehensive diagnostic approach to ensure timely diagnosis and appropriate management.”
The case study, “Fabry Disease in a Female: A Unique Case Highlighting the Variability in Clinical Presentation,” was published in Cureus.
Fabry is a rare disease caused by mutations in the GLA gene that affect the production of alpha-galactosidase A (Gal A) and results in a fatty substance called globotriaosylceramide (Gb3) accumulating inside cells. Gb3 can build up in virtually any organ and tissue, leading to a wide range of Fabry signs and symptoms, including problems with the skin, eyes, heart, nervous system, kidneys, and gastrointestinal tract.
“Historically, females were considered to be asymptomatic [without symptoms] carriers of defective GLA genes who were not vulnerable to the symptoms and vital organ abnormalities,” the researchers wrote.
This was because the GLA gene is located within the X chromosome and women have two X chromosomes, while men have only one. A non-mutated GLA gene in one X chromosome could potentially compensate for the other chromosome’s mutated gene in women, but men having a single mutated GLA gene would always get the disease.
However, increasing evidence shows women carrying only one mutated copy of the GLA gene “can exhibit a broad spectrum of clinical presentations, ranging from the complete absence of symptoms to a full manifestation of the classic disease,” said the researchers. Womens’ symptoms may manifest differently and often emerge more subtly later in life and progress slower, which causes researchers to believe Fabry disease is underdiagnosed in women. This is a problem because early diagnosis and treatment are key to reducing organ damage and improving long-term clinical outcomes.
A diagnosis of Fabry disease
Here, researchers in India describe the rare case of a 32-year-old woman with Fabry disease who showed a wide range of symptoms.
The woman sought medical treatment at an emergency room because of progressive shortness of breath for 10 days, a fever for four days, and headache, lower limb pain, and swelling around the eye for three months. She’d previously been diagnosed with high blood pressure (hypertension) and chronic kidney disease.
An examination confirmed hypertension and fever, and showed her heart rate and breathing were abnormally fast. She also reported parasthesia, or sensations of tingling, burning, prickling, itching, or numbness. Bloodwork showed the woman had lower levels of hemoglobin, the protein in red blood cells that transports oxygen throughout the body.
Further analysis revealed substantial impairments in her kidney function, based on elevated protein levels in the urine and elevated levels of urea and creatine in the blood. A kidney biopsy was taken to identify the underlying cause of these issues and clinicians found increased tissue stiffness in her kidneys and larger than normal podocytes, a type of kidney cell that wraps around blood vessels to help filter waste and fluid from the blood. Kidney cells also showed zebra bodies, a hallmark of Gb3 buildup in cells.
The findings, along with her symptoms, led clinicians to diagnose the woman with Fabry disease.
She was prescribed hemodialysis, a kidney-replacement procedure that filters blood to remove waste and excess water from the blood, and drugs to help flush excess water and salt through her urine. The woman was also given medication for her hypertension. Her condition improved and she was discharged, but continued to have hemodialysis, and regular follow-up assessments were scheduled.
“This case is a rare and unique example of Fabry disease in a female patient, with symptoms affecting multiple organ systems, including the renal, cardiovascular, and neurological systems,” the researchers wrote, adding it also “illustrates the significance of recognizing Fabry disease in female patients, highlighting the need for heightened clinical awareness.”
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