Dr. Chafic Karam, professor of neurology from the University of Pennsylvania, provides an informative overview of how certain mutations of hereditary transthyretin amyloidosis are being diagnosed in the central nervous system (CNS), such as the eye. It has been long believed that amyloidosis did not cross the blood brain barrier; however, evidence is showing otherwise. In addition, while most of the transthyretin protein originates in the liver, local production is found in other areas of the body such as the brain and retina. Dr. Karam will discuss how patients might present, the developing state of diagnostics, and treatments available. A slower developing symptom, with patients now living longer he predicts neurologists will see more and more patients with CNS and ocular involvement.
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Expert Insights: Timing and co-occurrence of red-flag symptoms prior to a diagnosis of light chain (AL) amyloidosis
Dr. Anita D’Souza, associate professor of hematology and medical oncology from the Medical College of Wisconsin, discusses recent study findings regarding the timing and co-occurrence of symptoms within the three years prior to a diagnosis of light chain (AL) amyloidosis. Organized by organ system, Dr. D’Souza lists red-flag symptoms that patients may experience, typically presenting in varying combinations. Analyzing EHR records she sought to understand whether red-flag symptoms were indeed being identified, and how their occurrence would accumulate over time towards diagnosis.
Bottom line:
- This work confirms that patients are being diagnosed within the healthcare system with multiple red-flag diagnoses before AL amyloidosis is formally diagnosed.
- It is possible to catalog these diagnoses from electronic health records data and thus has the potential for earlier diagnosis of this complex disease.
- This study shows the timing and combinations between these diagnoses and lays the foundation to develop clinical algorithms aimed at earlier recognition of AL amyloidosis.
Congressional Hill Briefing, Improving Care for Veterans with Rare Diseases: Establishing a National Commission
We, with other members of the amyloidosis community, were proud to join an important meeting hosted by the Center for Patient Advocacy Leaders (CPALs). They hosted a Congressional Hill Briefing, Improving Care for Veterans with Rare Diseases: Establishing a National Commission, at the U.S. Capitol Visitor Center in Washington, DC. This briefing was designed to bring together Veterans/Veterans’ advocates, rare disease advocates, patients, and congressional staff to address unmet needs of Veterans with rare diseases and explore collective action to help ensure Veterans with rare diseases get the comprehensive, patient-centered care and treatment they need and deserve.
Expert Insights: Systemic Amyloidosis: You’ve Got to Think of IT to Diagnose IT
Dr. Mat Maurer, cardiologist at Columbia University Irving Medical Center, discusses the importance of developing a broad differential in order to diagnose this rare, potentially life-threatening, yet treatable disease. He shares a typical but unfortunate case of cardiac amyloidosis, along with statistics of misdiagnosis and delayed diagnosis. He shares his view on the appropriate process for diagnosis based on Dr. David Eddy’s 1982 New England Journal of Medicine piece “The Art of Diagnosis” and the need to create a broad enough differential in order to consider less common diseases such as systemic amyloidosis. Dr. Maurer lists common reasons for missing diagnosis of cardiac amyloidosis all clinicians should be aware of, punctuated by his concluding point … “The Key to Correct Treatment is Diagnosis, Diagnosis, and Diagnosis.” It’s simple … you cannot treat what has not been diagnosed.
This is a MUST VIEW video for clinicians who diagnose patients, regardless of sub-specialty.
ATTR-CM (cardiomyopathy) vs ATTR-PN (peripheral neuropathy)
Over the course of the past few months, we spent time discussing two of the most common hallmark symptoms of ATTR amyloidosis: cardiomyopathy and peripheral neuropathy. In this article, we’ll briefly recap both hallmark symptoms as well as bring it all together by discussing the two most common forms of ATTR amyloidosis: ATTR cardiomyopathy (ATTR-CM) and ATTR peripheral neuropathy (ATTR-PN).
To recap …
Cardiomyopathy
Cardiomyopathy is a broad term that is used to describe disease of the heart muscle, making it difficult for the heart to provide the body with an adequate blood supply. It is a common cause of sudden cardiac arrest and sudden cardiac death, which can lead to heart failure and even death.
Types of Cardiomyopathy:
- Dilated Cardiomyopathy → dilation of the left ventricle prevents the heart from pumping effectively
- Hypertrophic Cardiomyopathy → abnormal thickening of the heart muscle most commonly surrounding the left ventricle
- Restrictive Cardiomyopathy → stiffening of the heart muscle results in an inelasticity
- Arrhythmogenic Right Ventricular Dysplasia → scar tissue replaces healthy tissue of the right ventricle
- Unclassified Cardiomyopathy → all other forms of cardiomyopathy fall within this category
Peripheral Neuropathy
Peripheral neuropathy, also referred to as polyneuropathy, is a very broad term used to describe damage of the peripheral nerves. Damage to these nerves most commonly causes numbness, pain, and weakness but can affect other areas of the body including, but not limited to, circulation, digestion, and urination.
Types of Neuropathy:
- Motor Neuropathy → damage to the motor nerves
- Sensory Neuropathy → damage to sensory nerves
- Autonomic Nerve Neuropathy → damage to autonomic nerves that control involuntary functions
- Combination Neuropathies → damage to a mix of 2 or 3 of these other types of neuropathies
ATTR Amyloidosis
The origin of this disease can be genetic (hATTR) or non-genetic, or “wild-type” (ATTRwt). Regardless, in ATTR amyloidosis, the transthyretin (TTR) protein is misfolded and aggregates, forming amyloid fibers that deposit into tissues and organs. The deposition of protein causes organ dysfunction and can even cause organ failure and death.
ATTR-CM and ATTR-PN
Depending on the location of protein deposition, the disease is referred to in different ways. For instance, when the primary location of amyloid deposit is in the heart, the disease is referred to as ATTR cardiomyopathy (ATTR-CM). On the other hand, when the primary location of amyloid deposit is in the nerves, the disease is referred to as ATTR peripheral neuropathy (ATTR-PN).
ATTR-CM impairs the heart’s ability to pump effectively. A major challenge surrounding this disease is that symptoms of ATTR-CM are often similar to other heart conditions like enlarged heart and heart failure. This makes diagnosing the disease increasingly more difficult. Individuals with hATTR typically present symptoms in their 50s and 60s, whereas those with ATTRwt may not present symptoms until their 70s and later.
Common Symptoms of ATTR-CM:
- Fatigue
- Swelling of legs, ankle, or abdomen
- Shortness of breath with activity
- Orthostatic hypotension
- Difficulty breathing when lying down
- Arrhythmia
ATTR-PN impairs the function of the nervous system. While amyloid most commonly builds up in the peripheral nervous system, deposition can also occur in the autonomous system. This results in a diversity of symptoms that are specific to the site of amyloid deposition. Symptom presentation is much more diverse, occurring as early as the 20s, or as late in life as the 70s.
Common Symptoms of ATTR-PN:
- Carpal tunnel syndrome
- Diarrhea and/or constipation
- Nausea, vomiting
- Loss of appetite
- Sexual dysfunction
- Muscle weakness
- Eye problems
- Orthostatic hypotension
Expert Insights – Cardiac Clues and Clinical Signs
In part 1 of a 2-part series, Dr. Keyur Shah, cardiologist from VCU Health’s cardiac amyloidosis care team, discusses the two most common types of transthyretin (TTR) amyloidosis: hereditary and wild-type. He details how ATTR cardiomyopathy amyloidosis presents and manifests itself to impair the heart. Dr. Shah lists clinical clues, “red flags,” and biomarkers which can raise suspicion of the presence of amyloidosis. Next, he discusses insights that can be gained from echocardiograms, electrocardiograms, and cardiac MRIs and how they offer possible indicators of the disease presence. Once amyloidosis is suspected, definitive diagnosis testing is next.
In part 2 of a 2-part series, Sarah Paciulli, Heart Failure Nurse Practitioner, from VCU Health’s cardiac amyloidosis care team, continues from where Dr. Keyur Shah ended in Part I and discusses here in Part II the non-cardiac clues of transthyretin (TTR) amyloidosis. She expands the list of clinical clues and “red flags” that clinicians should be alert to, including orthopedic manifestations, erectile dysfunction, and polyneuropathy.
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References:
https://www.pfizer.com/news/articles/understanding_this_rare_disease_called_attr_amyloidosis
https://www.mayoclinic.org/diseases-conditions/cardiomyopathy/symptoms-causes/syc-20370709
https://www.yourheartsmessage.com
https://healthjade.net/familial-amyloidosis/
https://my.clevelandclinic.org/health/diseases/14737-neuropathy
https://www.hopkinsmedicine.org/health/conditions-and-diseases/peripheral-neuropathy
https://www.mayoclinic.org/diseases-conditions/peripheral-neuropathy/symptoms-causes/syc-20352061
https://practicalneurology.com/articles/2021-july-aug/neuromuscular-amyloidosis
https://healthjade.net/familial-amyloidosis/
Patient Insights: My survival depends on my physicians communicating
Our patient speakers at the Amyloidosis Speakers Bureau are powerful educators and offer compelling insights. Have a listen to this brief clip from Rayna. She talks about how important she felt it was for her survival that her physicians communicated.
Expert Insights: The Systemic Amyloidoses vs. Parkinson’s vs. Alzheimer’s
Current medical education on amyloid diseases is 25 years old and materially outdated, punctuated by rapid advancement in the last five years. Hear from renowned Dr. Jeff Kelly from Scripps Research, developer of ATTR drug tafamidis, about the current biology and how amyloid diseases such as the Systemic Amyloidoses (ATTR and AL), Parkinson’s and Alzheimer’s are today believed to be more similar than different.
For those interested in learning more about neurodegenerative diseases driven by amyloid protein misfolding, below is an excellent video from May 17, 2024 by Dr. Kelly.
Expert Insights: AL Amyloidosis: Symptoms, Diagnostics and Challenges
Dr. Gurbakhash Kaur, co-director of the amyloidosis program at UT Southwestern Medical Center, opens with a brief overview of the disease. Focusing on AL Amyloidosis, she shares how heterogeneously this disease presents – it can be very different from patient to patient, amplifying the diagnostic challenge. Symptoms may also be more commonly associated with other diseases. For example, proteinuria is often associated with diabetes and hypertension. However, clinicians should look at the bigger picture to be sure, as amyloidosis can also be a cause. Dr. Kaur reviews what should be in a basic workup when one has a clinical suspicion for amyloidosis. Once tested positive for amyloidosis, a second necessary step is to determine the type of amyloidosis. This is critical as it will determine the appropriate course of treatment. In closing Dr. Kaur summarizes the goals of treatment, what is available today, and what drugs are in clinical trials, giving lots of hope to the AL amyloidosis community.
Diagnosing Amyloidosis: From Cardiology to Neurology – When to Think About Amyloidosis
Dr. J. Mark Sloan, Associate Professor of Medicine, Boston University Chobanian & Avedisian School of Medicine. He is a member of the BU Amyloidosis Center, the Evans Center for Interdisciplinary Biomedical Research at BU, and the program director for the hematology/oncology fellowship at Boston University. In this video, developed exclusively for the Amyloidosis Speakers Bureau, he provides a comprehensive clinical overview of diagnosing amyloidosis, from cardiology to neurology, and when to think about amyloidosis.
AL and ATTR Amyloidosis: Recognition and Diagnosis — The Key to Successful Treatment
Dr. Heather Landau, Associate Attending Physician at Memorial Sloan Kettering, provides a comprehensive clinical overview of amyloidosis. Spanning recognition and diagnosis – the key to successful treatment.
