What are some of the most common rare diseases?

Rare diseases aren’t as rare as you might think. Millions of Americans live with conditions that individually affect relatively small numbers of people yet collectively impact a significant portion of the population. Understanding these diseases and their management is increasingly important for healthcare providers and life sciences companies alike.

What is a rare disease?

In the U.S., the Orphan Drug Act of 1983 defines a disease as “rare” if it affects fewer than 200,000 people. Around 1 in 10 Americans lives with at least one of more than 7,000 rare diseases.

Let’s explore five of the most common rare diseases affecting patients in the U.S., according to estimates from the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH).

The most common rare diseases in the U.S.

1. Muscular dystrophy

Muscular dystrophies (MD) are a group of genetic disorders characterized by progressive muscle weakness and degeneration. Duchenne Muscular Dystrophy (DMD) is the most common of these disorders, primarily affecting young boys with symptoms usually appearing around age four.

Although relatively rare, around 250,000 people in the U.S. live with some type of MD. These patients require ongoing, complex care for both mobility and respiratory support. Providers can make the biggest impact by identifying symptoms early. Offering coordinated, multidisciplinary care can help improve quality of life and slow disease progression. Care teams that are unable to staff a specialist in the disease should consider partnering with MD experts who are up to date on the latest treatments and research.

While there’s no existing cure for MD, and related muscle damage can’t be reversed, gene therapy could eventually enable doctors to replace young patients’ mutated genes with healthy copies before the disease progresses.

2. Sickle cell disease

Sickle cell disease (SCD) impacts around 100,000 Americans, primarily those of African American and Hispanic descent. This genetic blood disorder distorts red blood cells into a sickle-like shape, causing painful episodes or “crises”, organ damage, and increased infection risk.

As with muscular dystrophy, early intervention and regular monitoring are crucial for managing symptoms and maintaining quality of life. SCD pain crises can be triggered by certain everyday factors, including stress, dehydration, alcohol and tobacco, and even other sources of pain. Because of the self-managed nature of these triggers, early patient education is critical—and also among the biggest challenges facing doctors treating rare diseases, according to our report.

Aside from education and making lifestyle changes to avoid triggers, gene therapy is among the most promising sources of relief for SCD patients. Vertex Pharmaceuticals’ Casgevy (exagamglogene automecel) treatment uses a patient’s blood stem cells to help their body produce functional red blood cells and reduce or eliminate pain crises.

3. Primary biliary cholangitis

Affecting approximately 65,000 people in the U.S., primary biliary cholangitis (PBC) is a rare autoimmune disease that causes a person’s body to gradually damage—and eventually destroy—bile ducts within the liver. Over time, this process leads to cirrhosis of the liver and other symptoms like itching, dry eyes and mouth, and raised cholesterol levels.

PBC predominantly impacts women over 40 and, like the other diseases we’ve covered, is best managed when detected early. Specialized hepatologists can usually diagnose the disease with a blood test, but medical imaging or more direct examinations of the liver may be necessary.

PBC currently has no cure, but ursodeoxycholic acid can mitigate damage to the liver when taken as an early treatment. In the most extreme cases, a liver transplant may be necessary.

4. Cystic fibrosis

The genetic disorder cystic fibrosis (CF) primarily affects the respiratory and digestive systems, making it difficult for the lungs and gastrointestinal tract to clear mucus. Around 40,000 people in the U.S. live with CF, dealing with frequent lung infections, breathing difficulties, and nutritional deficiencies that can hinder daily life and make physical exertion difficult to tolerate.

The whole-body impact of CF requires providers to adopt a multidisciplinary approach to treatment, with particular focus on pulmonary care, nutrition, and physical therapy. Treatment includes an array of medications for symptoms like respiratory infections and mucus buildup, airway clearing techniques, and lifestyle changes.

Advances in CF care and early diagnosis (newborn screening is increasingly common) have considerably extended patients’ life expectancies, and gene therapy may eventually provide a one-time cure, but for now, lifelong disease management remains necessary. For providers looking to grow their rare disease expertise, CF represents a high-value focus area given this need for comprehensive, long-term care.

5. Huntington’s disease

Unlike the other rare diseases on this list, Huntington’s disease is a neurodegenerative disorder. Inherited through a parent, Huntington’s disease is caused by a faulty gene that directs neurons in the brain to deteriorate and die, resulting in progressively declining muscle coordination, cognition, and mental health.

For the 40,000 Americans living with Huntington’s disease, careful, ongoing attention from medical specialists is crucial to manage symptoms. An effective interdisciplinary team could include neurologists, behavioral health specialists, and physical therapists, in addition to primary care physicians. Over time, most patients will require a part- or full-time caregiver to support their basic activities of daily living, who will also benefit from medical support and education.

Although Huntington’s disease has no cure, gene therapy and stem cell therapy can help reduce the production of the mutant protein responsible for the disease’s degenerative effects. As rare disease research progresses, these therapies may eventually offer a full cure.

Implications for healthcare and life sciences

Rare diseases present some of the most complex challenges in healthcare, in part because patients are few, geographically dispersed, and often treated across multiple specialty settings. For health systems, this fragmentation makes it difficult to know where expertise exists or where gaps in care may create preventable delays.

Detailed claims data as well as provider and facility-level data can bring rare disease patient journeys into focus, showing not only where care occurs but also how referrals move between specialists and where coordination gaps exist.

With this kind of insight, health systems can make choices grounded in evidence: where to invest, when to partner, and how to reduce friction across episodes of care. The right data can also open the door to connecting local clinicians with centers of excellence (COEs) and designing care pathways that evolve alongside patient needs.

Life sciences companies face a parallel challenge: demonstrating value and achieving adoption for therapies that target small populations. Even with regulatory incentives like orphan drug designation, the commercial and clinical success of a therapy hinges on reaching the right providers and ensuring patients can access treatment.

Detailed market intelligence can help companies in the rare disease space identify not just the largest potential patient pools, but also the clinicians most influential in treatment decisions. Understanding facility capabilities, referral networks, and treatment patterns can inform everything from trial site selection and educational outreach to post-market support, reducing uncertainty in what is otherwise a high-risk investment.

Ultimately, rare diseases are as much a data challenge as a scientific one. Leveraging data and insights can give health systems and life sciences organizations a clearer view of patient populations and treatment opportunities, helping patients get the care they need while making it easier for therapies to reach the people who need them.

Navigate rare disease care more effectively

Definitive Healthcare offers diagnosis and procedure claims data that can help you identify opportunities for growth and strategic focus in your market, as well as population intelligence featuring health attributes and predictive market analytics. Sign up for a free trial today and see how our healthcare commercial intelligence platform makes it easier to provide effective and efficient care in the rare disease space.