Exploring the nephrologist’s role in the diagnosis and treatment of Fabry disease
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Nephrologists often see patients with common or well-known conditions, including kidney stones, diabetes, high blood pressure and urinary tract infections.
It is less often that we are faced with diagnosing and treating rare diseases, given the limited impact on a small number of patients. It makes patient care challenging as a result.
Some rare diseases, such as Fabry disease, a lysosomal storage disorder, can also cause symptoms (like renal impairment) that are like those of more common conditions. Fabry disease is a complex, multi-systemic disease impacting several different parts of the body in addition to the kidneys.
I have treated patients with Fabry disease for almost 15 years and have found nephrologists can play key roles in identifying and managing the condition. Given the multifaceted nature of Fabry’s disease, inter-specialist communication is critical to ensure an early and accurate diagnosis and optimal patient outcomes.
Rare disease community
Fabry disease is relatively well known in the rare disease community but may be lesser known among the general population. It is an inherited X-linked disorder that occurs in about one of every 40,000 to 60,000 people worldwide. The disease is caused by a genetic mutation in the alpha-Galactosidase-A (GLA) gene, resulting in a deficiency of the GLA enzyme. This leads to the abnormal buildup of a fatty substance called globotriaosylceramide (Gb3) in the lysosomes throughout the body.
Initial symptoms of Fabry disease typically begin in childhood and can include pain in the hands and feet, dark red spots on the skin, an inability to sweat and cloudiness in the front part of the eye. As patients get older, they often develop heart complications, a high risk for strokes, digestive difficulties and severe pain and kidney problems that can eventually lead to renal failure.
Among the multiple systemic symptoms that Fabry disease can cause, the NIH has found the condition impacts kidney health in almost all male and many female patients. Patients with Fabry disease can begin experiencing reduced kidney function in early childhood, and it is often the first sign of the disease. Renal manifestations progress over time and can include proteinuria, albuminuria, a decreased GFR or the presence of renal cysts as shown by an MRI or CT scan.
In cases of mild renal impairment, symptoms may be managed with a low-salt diet. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can also be used to mitigate kidney damage in cases of proteinuria or if a patient’s blood pressure is high. If kidney damage cannot be effectively managed with diet modifications or medication, end-stage kidney failure may result, requiring dialysis or kidney transplantation.
Communication
Fabry disease can vary in terms of severity and symptoms from patient to patient, making diagnosis difficult. While our instinct as nephrologists is to focus solely on the kidney manifestations, it is important to take a holistic view of a patient’s symptoms, as well as a medical history to reach an accurate diagnosis. It is possible the answer is not straightforward and the cause may be a rare disease, such as Fabry disease. Collaboration with all members of a patient’s care team, including other specialists, is key, especially when multiple symptoms present.
In many cases, diagnosing Fabry disease requires nephrologists to collaborate and communicate with a diverse team of other medical professionals, including cardiologists, neurologists and pain management specialists. But the engagement of multiple specialists can present significant challenges. In some cases, lines of responsibility and decision-making procedures can be complex. Patients may not be well informed about the role of each specialist in their care, and they may also fail to discuss relevant issues with all or the appropriate members of their care team.
It is important nephrologists and other specialists identify one another and keep in constant contact to align and streamline care. Specialists must establish guidelines on how to best coordinate disease management and treatment across functions.
Misconceptions
Inter-specialist communication is key to identifying and addressing symptoms early and correctly diagnosing patients. For Fabry disease, misdiagnosis is common, with many patients going undiagnosed until the age of 20 or 30 years old, despite exhibiting symptoms during the pre-teen years.
Ongoing communication among specialists is also essential for continued medical education and building broader awareness of diseases. For Fabry disease, sharing information and learnings can help address any misconceptions, such as it only impacts men.
In the past, the medical community believed women could not have X-linked diseases, such as Fabry disease. But about half of my patients with Fabry disease are women and experience many of the same debilitating symptoms as men.
In addition, nephrologists and other specialists must recognize their role in updating patients with Fabry disease about available treatments, advances in research and opportunities to participate in clinical trials.
Treatment
There are currently several enzyme replacement therapies (ERTs) approved for Fabry disease in the United States. However, there are some limitations with first-generation ERTs that physicians must keep in mind. For example, patients can continue to lose kidney function despite being on treatment.
Some ERTs also may not effectively penetrate all tissues, have a limited impact on treatment of cardiac issues. Some patients also continue to experience neuropathic pain, and bouts of diarrhea, nausea and vomiting. Others also continue to rely on opioids to help manage their chronic pain and severe pain episodes.
Progress
Given the limitations with traditional ERTs and perspectives provided by patients under my care, there is a clear continued unmet need for new treatment options in Fabry disease. There are several investigational therapies in development, that are promising and in May the FDA and European Commission approved a novel ERT based on a plant-based platform used to produce the recombinant version of the alpha-Gal A protein. Research and development of new potential treatment options is encouraging, and it is exciting to see continued progress, which may ultimately impact our roles as specialists and our care plans for patients with Fabry disease.
It is important that nephrologists continue to collaborate with other specialists, including cardiologists and neurologists to not only increase disease education and diagnose Fabry disease sooner, but to also share information about available treatments, ongoing clinical research, new studies and investigational therapies that might benefit patients who are inadequately treated with some available ERTs.
Nephrologists also must listen to patients’ perspectives and provide them with a wide range of resources and insights to help them play a role in making the optimal decisions about their health and treatment plans. Collaboration, whether among specialists, patients or other stakeholders, is key to reaching the goal of improving patient quality of life.
- For more information:
- Ankit N. Mehta, MD, is the program director for the department of internal medicine at Baylor University Medical Center in Dallas and is involved in research at Baylor Scott & White Health. He practices nephrology with Dallas Nephrology Associates and can be reached at ankit.mehta@bswhealth.org.
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