Death of bone tissue a rare, painful Fabry complication: Case report
Man experienced severe pain and mobility problems, required hip replacements
A type of bone tissue death called avascular necrosis is a rare and painful complication of Fabry disease that clinicians should be aware of, according to a recent case report.
The report described a 41-year-old man with Fabry who experienced severe pain and mobility problems from avascular necrosis, and ended up needing his hips replaced.
“We expand awareness of early [avascular necrosis] as a potential new complication of Fabry disease in a young patient,” researchers wrote.
The report, “Bilateral avascular necrosis: A rare complication of Fabry disease,” was published in Molecular Genetics and Metabolism Reports.
Fabry disease caused by gene mutations
Fabry disease is caused by GLA gene mutations that ultimately lead to the harmful accumulation of a fatty molecule called globotriaosylceramide (Gb3) inside cells.
In Fabry disease, Gb3 accumulation can happen in essentially any tissue, leading to a wide range of symptoms, but it commonly affects the kidneys, heart, nerves, skin, and eyes.
Although less well-recognized, the bones can also be affected, and people with Fabry are at an increased risk of osteopenia, or low bone density, and osteoporosis, where bones become weak and fragile from bone loss.
Avascular necrosis where bone tissue death is directly related to insufficient blood supply, is a rare complication, but one that can cause pain, fractures, and mobility issues if not addressed.
The man in the case report had been diagnosed with Fabry at 25. A disease-causing mutation was identified, and the disease ran in the family.
He experienced a wide range of symptoms and had been treated with enzyme replacement therapy (ERT) since the age of his diagnosis. In the last few years, he had been on lisinopril to manage heart complications.
Patient had both hips replaced
Imaging done at age 38 showed the man had osteopenia in the upper part of the thigh bone that connects to the hip (femoral head) and in part of the spine. His vitamin D levels were low, which can affect bone health, and he sporadically took vitamin D supplements.
At 39, the man underwent additional imaging because he was experiencing persistent right hip pain without any known injury. He reported the pain was interfering with his daily activities, and was accompanied by sounds of popping, clicking, and grinding.
Imaging revealed signs of avascular necrosis in both hips. He underwent a right hip replacement surgery. The left hip kept getting worse and more painful, however, and he eventually also had a left hip replacement. Analysis of the bone revealed signs of substantial bone death.
The scientists said while the exact mechanisms through which avascular necrosis arises in Fabry aren’t known, there are a few factors that may contribute.
First, it could be related to Gb3 accumulation in the femoral head. Avascular necrosis has similarly been associated with other diseases where waste products harmfully accumulate, particularly Gaucher disease. An early start to ERT can help reduce that buildup to avoid such complications, the scientists noted.
In addition, people with Fabry disease are at an increased risk of blood clots, which can impede blood flow and contribute to avascular necrosis. Use of aspirin (acetylsalicylic acid) can help prevent blood clots.
The authors noted the man in this study reported moderate alcohol intake, which is a known avascular necrosis risk factor.
Ultimately, the case highlights a need for clinicians to be aware of the entire clinical spectrum of Fabry to ensure prompt and accurate diagnoses. This will allow for the earliest possible launch of preventive treatments to avoid complications like avascular necrosis.
“Early diagnosis, treatment with ERT, intervention and proactive management of osteoporosis, and thromboprophylaxis [blood clot prevention] with acetylsalicylic acid and avoidance of alcohol are crucial to preventing [avascular necrosis] in this patient population,” the team concluded.
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