Explore below for information on the diseases within our areas of focus.
Rare diseases are diseases that affect a small percentage of the population.
The threshold at which a disease is considered rare varies around the world. In the United States, the Rare Diseases Act of 2002 defines a rare disease as “any disease or condition that affects fewer than 200,000 people in the United States.”1
The common consensus is that there are approximately 7,000 types of rare diseases. While individual diseases may only affect a small number of patients, taken together, they are far more common. Approximately 30 million Americans – ten percent of the population – are living with a rare disease.2
For patients and caregivers, rare diseases can pose significant challenges.
- 80% of rare diseases are genetic2
- 50% of patients affected by rare diseases are children2
- Only about half of rare diseases have a disease-specific foundation dedicated to support, advocacy and research2
- Over 95% of rare diseases lack a single FDA-approved drug treatment3
- Rare Diseases Act of 2002. https://www.congress.gov/bill/107th-congress/house-bill/4013/text.
- RARE Diseases: Facts and Statistics. Global Genes. https://globalgenes.org/rare-diseases-facts-statistics/ Accessed May 15, 2017.
- Miyamoto BE, Kakkis ED. The potential investment impact of improved access to accelerated approval on the development of treatments for low prevalence rare diseases. Orphanet Journal of Rare Diseases. 2011;6(1):49. doi:10.1186/1750-1172-6-49.
Chronic granulomatous disease (CGD) is a rare genetic disease that affects the immune system. In people with CGD, the immune system isn’t working like it normally does. So, it is very hard for the body to fight off life-threatening infections from bacteria and fungi, which are called pathogens. That’s why people with CGD are at a higher risk for getting serious, unusual, and repeat infections.
Often, people with CGD also have inflammatory problems, like inflammatory bowel disease and granulomas. Granulomas are hard lumps that build up in the tissue. They can cause serious harm to the body in places like the intestines, bladder, and lungs.
Today with treatment, CGD is known to be a condition that most patients can manage. Studies suggest overall survival has improved over the last decade with more patients living well into adulthood.1 The estimated incidence of CGD is 1 in 200,000 people born in the United States.1
Signs and Symptoms of CGD
An individual may begin to show signs of CGD anytime from infancy to adulthood. However, the vast majority of patients are diagnosed before 5 years of age.2
The signs and symptoms of CGD may include2:
- Slow growth in childhood
- Infections caused by specific types of bacteria or fungi that affect the lungs, lymph nodes, liver, bones, or skin, which are often severe, occur spontaneously, and recur frequently
- The formation of granulomas, particularly in the bladder and gastrointestinal tract
- Colitis (inflammation of the colon)
- Wounds that heal abnormally caused by excessive formation of lumps (granulomas) in the tissue
Testing for CGD
A doctor who suspects a person might have CGD may order a lab test that assesses the activity of phagocytes.2
The dihydrorhodamine (DHR) test2
Today, the DHR test is the preferred method for diagnosing CGD. In this blood test, white blood cells (phagocytes) are exposed to the chemical dihydrorhodamine (DHR) and measured using a process called flow cytometry. Normal white blood cells will emit a fluorescent light, which means the cells produce the chemical needed to kill harmful microorganisms. If the cells do not emit a fluorescent light, it indicates the cells do not produce, or do not produce enough of, the chemical needed to kill the microorganisms, which means the patient could have CGD.
CGD is a chronic disease; however, its symptoms can be managed through2:
- Year-round prophylaxis with doctor-prescribed medications to help prevent serious infections
- Careful lifestyle choices to avoid potentially harmful activities and environments
- Regular checkups with a physician to facilitate early intervention as necessary
People who have CGD are highly susceptible to severe recurrent infections, which can often require hospitalization and special disease management.2,3 The most important goal in managing patients with CGD is to prevent infections.
- Winkelstein JA, Marino MC, Johnston RB Jr, et al. Chronic granulomatous disease: report on a national registry of 368 patients. Medicine (Baltimore). 2000;79(3):155-169.
- Leiding JW, Holland SM. Chronic granulomatous disease. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT,Stephens K, eds. GeneReviews. Seattle, WA: University of Washington; 2012.
- Song E, Jaishankar GB, Saleh H, Jithpratuck W, Sahni R, Krishnaswamy G. Chronic granulomatous disease: a review of the infectious and inflammatory complications. Clin Mol Allergy. 2011;9(1):10.
There are several different forms of osteopetrosis (not to be confused with the more common osteoporosis, a very different condition), which are determined by their pattern of genetic inheritance and characteristics. All forms of osteopetrosis are characterized by an abnormal increase in bone density.1
Severe, malignant osteopetrosis (SMO) is one form of osteopetrosis and is sometimes referred to as marble bone disease or malignant infantile osteopetrosis (MIOP) because it occurs in very young children. Severe, malignant osteopetrosis is a more severe form of malignant osteopetrosis.*1,2
While exact numbers are not known, it has been estimated that 1 out of 250,000 children are born with severe, malignant osteopetrosis.1
During normal bone development, existing bone material is constantly being replaced by new bone. Cells called osteoblasts cause new bone formation. Other cells called osteoclasts remove old bone through a process called resorption.1
In people with osteopetrosis, this balance is not maintained because their osteoclasts do not function properly. As a result, resorption of old bone material decreases while the formation of new bone continues. This leads to an abnormal increase in bone mass, which can make the bones more brittle. Because abnormal bone development affects many different systems in the body, osteopetrosis may cause problems such as1,2:
- Blood disorders
- Decreased ability to fight infection
- Bone fractures
- Problems with vision and hearing
- Abnormal appearance of the face and head
In SMO, the abnormal accumulation of bone material tends to narrow the space inside bones where bone marrow is formed. This can cause failure of the bone marrow, leading to a decrease in various blood cells such as red blood cells (anemia) and white blood cells (decreased ability to fight infection). Also, there can be narrowing of the “tunnels” within bones of the skull (called foramina) through which the nerves for vision and hearing pass. When these nerves are compressed by the overdevelopment of bones due to SMO, vision and hearing problems can result.2
Patients with SMO often suffer serious effects from the disease. These may include1,2:
- Failure to thrive, slow growth in childhood
- Impaired vision or blindness
- Hearing loss
- Abnormal head shape
- Bone marrow failure, anemia
- Frequent and recurrent infections
- Frequent and recurrent bone fractures
SMO is associated with diminished life expectancy, with most untreated children dying within the first decade of their life.1
Severe, malignant osteopetrosis is generally diagnosed in infants, often within the first year of life. The first signs of the disease commonly noticed by parents are vision problems and failure to thrive or slow growth. Other early signs include recurrent infections, bone fractures, nasal congestion, and unusual facial features.2
To diagnose that a person has severe, malignant osteopetrosis, the doctor may order an X-ray. By examining the X-ray images, doctors can look for the abnormal bone development that is characteristic of the disease. That information combined with the patient’s physical signs and symptoms usually leads to a firm diagnosis. This diagnosis can be definitively confirmed through genetic testing.1
Therapies available for SMO can help to manage the complications that occur, delay progression of the disease, and prolong survival. Doctors may prescribe corticosteroid medications or high doses of calcitriol (a special form of vitamin D) in order to slow the progression of the disease. Problems caused by bone marrow failure may be treated with blood transfusions. Special treatments for vision, hearing, and dental problems may be required.1,2
Access information and support for Malignant Infantile Osteopetrosis (MIOP) by visiting the Ryan Western MIOP Foundation website.
- Stark Z, Savarirayan R. Osteopetrosis. Orphanet J Rare Dis. 2009;4:5.
- Wilson CJ, Vellodi A. Autosomal recessive osteopetrosis: diagnosis, management, and outcome. Arch Dis Child. 2000;83(5):449-452.
A urea cycle disorder (UCD) is an inherited metabolic disease caused by a deficiency of one of the enzymes or transporters that constitute the urea cycle. The urea cycle involves a series of biochemical steps in which ammonia, a potent neurotoxin, is converted to urea, which is excreted in the urine.1,2 When the urea cycle isn’t working properly, ammonia can’t be removed and continues to move throughout the body. This leads to ammonia building up in the blood – or “chronically elevated ammonia” – which can become dangerous because it can overflow from the liver into the rest of the body and cause permanent damage. UCD symptoms may first occur at any age depending on the severity of the disorder, with more severe defects presenting earlier in life.3
Urea Cycle Disorder Symptoms
UCD symptoms can be subtle and similar to many other conditions, which can lead to misdiagnosis. These symptoms can include headaches, fatigue (feeling tired), confusion and trouble concentrating. Any level of elevated ammonia, even if it’s not high enough to cause severe symptoms or a hyperammonemic crisis, should be avoided in order to prevent brain damage.
Managing a Urea Cycle DisorderFortunately, there are options for people with urea cycle disorders to help control high levels of ammonia in the body. Options can include a low-protein diet, amino acid supplements and ammonia-controlling medicines.
- Gropman, AL, et al. Neurological implications of urea cycle disorders. J Inherit Metab Dis 2007;30:865–869.
- Lanpher, BC, et al. Urea Cycle Disorders Overview. GeneReviews [Internet] 2011
- Häberle, J, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet Journal of Rare Diseases 2012;7:32.
Nephropathic cystinosis is a rare, metabolic disease which begins in infancy, affecting approximately 500 people within the United States, and roughly 2,000 people worldwide.1 This genetic condition may be present when an individual inherits two mutated copies—one from each parent2—of the CTNS gene, a gene responsible for providing the body with instructions for making a protein called cystinosin.3 Cystinosin helps move cystine in and out of the body’s cell compartments, called lysosomes. In people with nephropathic cystinosis, the amino acid cysteine is able to move into lysosomes, but is unable to move out of them. The cysteine molecules combine to form cystine, which then crystalizes and triggers cell death.1 The accumulation of cystine crystals cause damage to organs throughout the body such as the kidneys, eyes, liver, muscles and brain.4 It can also cause complications like muscle wasting, hypothyroidism, issues with swallowing, blindness and diabetes.3
Although appearing normal at birth, infants with nephropathic cystinosis may show symptoms of dehydration and excessive thirst, they may urinate frequently and exhibit excessive fussiness. Poor growth and kidney damage in the form of renal Fanconi syndrome are also common characteristics. If left untreated, kidney failure along with other complications such as blindness, diabetes, thyroid and central nervous system problems may occur.3
Diagnosing Nephropathic Cystinosis
Nephropathic cystinosis often goes undiagnosed and/or is misdiagnosed.4 There are many methods for testing elevated levels of cystine within cells; however, genetic testing—specifically, molecular analysis of the CTNS gene—can be used to detect the condition early and even for prenatal diagnosis.5
Managing Nephropathic Cystinosis
Management of nephropathic cystinosis involves the treatment of symptoms caused by the disease. People with this condition need to take in more fluid along with minerals, phosphates and Vitamin D to normalize electrolyte imbalances and prevent rickets. Supplementing with carnitine, a substance critical for energy metabolism and mitochondrial protection, can help to combat muscle weakness and low blood sugar.
- About Cystinosis. Cystinosis Research Foundation. Accessed May 30, 2017.
- Autosomal recessive inheritance pattern. Mayo Clinic. Accessed May 30, 2017.
- Cystinosis. Genetics Home Reference. Accessed May 30, 2017.
- Cystinosis: Symptoms & Treatment. Cystinosis Research Network. Accessed May 30, 2017.
- Cystinosis: practical tools for diagnosis and treatment. Martijn J. Wilmer, Joost P. Schoeber, Lambertus P. van den Heuvel, Elena N. Levtchenko Pediatr Nephrol. 2011 Feb; 26(2): 205–215. Published online 2010 Aug 24. doi: 10.1007/s00467-010-1627-6 PMCID: PMC3016220.
TED is a serious, progressive and vision-threatening rare autoimmune disease.1 TED often occurs in people living with hyperthyroidism or Graves’ disease; however, it is a distinct disease that is caused by autoantibodies activating an IGF-1R-mediated signaling complex on cells within the retro-orbital space.2,3 This signaling complex leads to severe inflammation and expansion of the connective tissue, muscle and fat cells behind the eye in the eye socket.4,5 This leads to a cascade of negative effects, which may cause long-term, irreversible damage – including proptosis (eye bulging), strabismus (misalignment of the eyes) and diplopia (double vision) – and in some cases can lead to vision loss.6,7
- Barrio-Barrio J, et al. Graves' Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management. Journal of Ophthalmopathy. 2015;2015:1-16.
- Weightman DR, et al. Autoantibodies to IGF-1 Binding Sites in Thyroid Associated Ophthalmopathy. Autoimmunity. 1993; 16(4): 251–257.
- Pritchard J, et al. Immunoglobulin Activation of T Cell Chemoattractant Expression in Fibroblasts from Patients with Graves’ Disease Is Mediated Through the Insulin-Like Growth Factor 1 Receptor Pathway. J Immunol. 2003;170:6348-6354.
- Bahn, R.S. Graves’ Ophthalmopathy. N Engl J Med. 2010;362:726-738.
- Tsui S, Naik V, Hoa N, et al. Evidence for an association between thyroid-stimulating hormone and insulin-like growth factor 1 receptors: a tale of two antigens implicated in Graves’ disease. J Immunol. 2008;181:4397-4405.
- Ross DS, et al. The 2016 European Thyroid Association /European Group on Graves' Orbitopathy Guidelines for the Management of Graves ' Orbitopathy. Eur Thyroid J. 2016;5(1):9-26.
- McKeag D, et al. Clinical features of dysthyroid optic neuropathy: a European Group on Graves ' Orbitopathy (EUGOGO ) survey. Br J Ophthalmol. 2007;91:455-458.
Osteoarthritis (OA) is a type of arthritis that is caused by the breakdown and eventual loss of the cartilage of one or more joints. Cartilage is a protein substance that serves as a cushion between the bones of the joints. OA is also known as degenerative arthritis. Among the over 100 different types of arthritis conditions, OA is the most common and occurs more frequently with age. Before age 45, OA occurs more frequently in males. After age 50, it occurs more frequently in females.1,2 OA commonly affects the hands, feet, spine and large weight-bearing joints, such as the hips and knees.2 Most cases of OA have no known cause and are referred to as primary OA.
Symptoms of OA manifest in patients as joint pain, tenderness, stiffness, limited joint movement, joint creaking (crepitation), locking of joints and local inflammation. OA can also lead to joint deformity in later stages of the disease.3 Many drugs, including NSAIDs, treat the signs and symptoms of OA, such as pain and stiffness.
- Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Maradit Kremers H, and Wolfe F for the National Arthritis Data Workgroup. “Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II.” Arthritis & Rheumatism. 2008;58(1):26-35.
- Centers for Disease Control and Prevention (CDC). “Osteoarthritis Fact Sheet” https://www.cdc.gov/arthritis/basics/osteoarthritis.htm.
- Arthritis Foundation. “Osteoarthritis Symptoms” http://www.arthritis.org/about-arthritis/types/osteoarthritis/symptoms.php.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints causing pain, stiffness, and swelling. In 2005, RA was estimated to affect approximately 1.3 million adults in the U.S. and has no known cause.1 RA occurs when the body’s immune system malfunctions, attacking healthy tissue and causing inflammation, which leads to pain and swelling in the joints, and may eventually cause permanent joint damage and painful disability. The primary symptoms of untreated RA include progressive immobility and pain, especially in the morning, with long-term sufferers experiencing continual joint destruction that can last for the rest of their lives.2 There is no known cure for RA, but there are many treatment options to control the disease. Once the disease is diagnosed, treatment is prescribed to slow or prevent disease progression and also alleviate symptoms.
RA treatments include medications, physical therapy, exercise, education and sometimes surgery. Early, aggressive treatment of RA can delay or prevent joint destruction. Treatment of RA usually includes multiple drug therapies taken concurrently. Disease modifying antirheumatic drugs, or DMARDs, and biologic therapies are the current standard of care for the treatment of RA, in addition to rest, strengthening exercise, and anti-inflammatory drugs. Methotrexate is the most commonly prescribed DMARD for the treatment of RA. Over the last decade, the advent of biologic agents has transformed the treatment of RA. Tumor necrosis factor, or TNF, inhibitors are the primary biologic agents used today to treat RA. Although effective for treatment of RA, these agents are very potent immunosuppressants and may increase the risk of infection.1
Other common agents for the treatment of RA include corticosteroids. Corticosteroids, such as prednisone, effectively reduce joint swelling and inflammation but are associated with potential for significant long-term dose-dependent side effects, such as osteoporosis, cardiovascular disease and weight gain. At high doses, these long-term adverse side effects are more frequent.
RA has the potential to cause serious damage to joints and bones and, as such, physicians typically treat patients aggressively, including with combination therapies to reduce pain and inflammation and to slow the progression of the disease. Recent research sponsored by Mundipharma and conducted by Ipsos MORI involving 750 RA patients from 11 European countries found that 60% of people with RA indicated that impaired morning function controls their lives. Additionally 18% of people surveyed were unable to work (i.e. retired early, on sick leave, or unemployed) as a result of RA and 58% of people with RA said that the inability or difficulty in doing things in the morning made them feel frustrated.3
An RA patient may take a combination of a DMARD, an oral glucocorticoid, an NSAID and/or a biologic agent. The majority of RA patients are treated with DMARDs. DMARDS, such as methotrexate, are typically used in initial therapy in patients with RA whereas biologic agents are typically added to DMARDs as combination therapy.4
- Helmick CG et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part I. Arthritis Rheum. 2008 Jan;58(1):15-25.
- “What is Rheumatoid Arthritis?” Arthritis Foundation. Accessed July 6, 2017.
- da Silva et al. Impact of impaired morning function on the lives and well-being of patients with rheumatoid arthritis. Scand J Rheumatol 2011;40 Suppl 125:6–11.
- Gorter SL, Bijlsma JW, Cutolo M, et al Current evidence for the management of rheumatoid arthritis with glucocorticoids: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis Annals of the Rheumatic Diseases 2010;69:1010-1014.
Polymyalgia rheumatica (PMR) is an inflammatory disorder involving aching and stiffness in patients over the age of 50 typically affecting the hips, shoulders and arms. Similar to rheumatoid arthritis, the symptoms associated with PMR such as stiffness are worse in the morning as compared to the rest of the day. However, unlike RA, glucocorticoid therapy is the most effective treatment currently available.1
- Mori S., Koga Y. Glucocorticoid-resistant polymyalgia rheumatica: pretreatment characteristics and tocilizumab therapy. Clin Rheumatol. 2016 May;35(5):1367-75.
Ankylosing spondylitis (AS) is a type of arthritis that primarily affects the sacroiliac joints (where the spine attaches to the pelvis), spine and hip joints.1 It causes inflammation of the spinal joints that can lead to severe, chronic pain and discomfort.1 In the most advanced cases, but not in all cases, this inflammation can lead to new bone formation on the spine, causing the spine to fuse in a fixed, immobile position, sometimes creating a forward-stooped posture.1 This forward curvature of the spine is called kyphosis.2
In addition to the spine and hips, AS can also cause inflammation, pain and stiffness in other areas of the body, such as the shoulders, ribs, heels and small joints of the hands and feet.1 Sometimes other parts of the body can become involved, such as the eyes (known as Iritis or Uveitis), and rarely, the lungs and heart can be affected.1 Currently, there is no known cure for AS, but there are treatments and medications available to reduce symptoms such as pain, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and tumor necrosis factor inhibitors.1
- About Spondylitis. Ankylosing Spondylitis. Spondylitis Association of America Website. http://www.spondylitis.org/about/as.aspx. Accessed July 6, 2017.
- Hoh DJ, Khoeuir P, Wang MY. Management of cervical deformity in ankylosing spondylitis. Neurosurg Focus. 2008;24(1):E9. doi: 10.3171/FOC/2008/24/1/E9.
Gout is a type of chronic inflammatory arthritis caused by too much uric acid in the blood. If uric acid levels in the blood are too high, thin rod-like crystals can form and deposit in the joints, which can lead to severe pain, tenderness, stiffness, swelling and joint damage.1 Over time these crystals can build up and form deposits of uric acid inside the body and joints, which can have harmful effects including causing damage to the underlying bone. The urate deposits are called tophi, and are not always clearly visible to patients or physicians. Sudden episodes of swelling and tenderness – often called gout flares – can also contribute to tophi.2
In addition to the joints, gout crystals can also deposit in other organs of the body,3 and if left unmanaged, gout can lead to significant and serious joint damage.4
Unfortunately, many people living with gout continue to have high levels of uric acid and gout symptoms despite the use of standard oral urate-lowering therapies (ULTs). This is known as uncontrolled gout. People living with uncontrolled gout may also have other significant health conditions, such as hypertension, chronic kidney disease, coronary artery disease and/or diabetes.5
Gout is typically classified as being uncontrolled when a patient continues to have symptoms of gout despite being on oral ULTs. Symptoms of uncontrolled gout can include:
- Uric acid level ≥ 6 mg / dL6
- Multiple gout flares – more than 2-3 per year7
- Visible tophi: uric acid crystal deposits which look like lumps under the skin8
- Pain that continues between flares1
Managing Uncontrolled Gout
The general goal for gout treatment is to keep uric acid levels lower than 6 mg/dL to prevent the build-up of uric acid crystals that cause gout flares, tophi, and bone/joint damage.8 For some patients who have greater disease severity, uric acid levels may need to be lower than 5 mg/dL.8
Treatment for uncontrolled gout includes a combination of lifestyle changes and medications. In addition, patients with uncontrolled gout often see a gout specialist, most commonly a rheumatologist. Rheumatologists focus on the treatment of joint diseases and are well-versed in the management of gout.8 Patients with Chronic Kidney Disease (CKD) can also speak to their nephrologist about treatment options for their uncontrolled gout.
Medical interventions to manage uncontrolled gout focus on getting a patient’s uric acid level below 6 mg/dL in order to stop additional uric acid crystals from building up and, ideally, to dissolve and remove crystals that have already built up in the body.9
- What is Gout? The Arthritis Foundation. Accessed June 1, 2017.
- Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63(10):3136-3141.
- Park J, Roudier M, Soman D, Mokada N, Simin P. Prevelance of birefringent crystals in cardiac and prostatic tissues, an observational study. BJM Open. 2014; 4:e005308. doi:10.1136/bmjopen-2014-005308
- Edwards NL. Treatment-failure gout: a moving target. Arthritis Rheum. 2008;58(9):2587-2590.
- Lisa K. Stamp, Peter T. Chapman; Gout and its comorbidities: implications for therapy. Rheumatology (Oxford) 2013; 52 (1): 34-44. doi: 10.1093/rheumatology/kes211.
- Khanna, et al, 2012 American College of Rheumatology Guidelines for the Management of Gout, Part. 1. Arthritis Care & Research Vol. 64, No. 10, October 2012, pp 1431–1446.
- Aaron T. Eggebeen. American Family Physician. Gout: An Update. 2007 Sep 15;76(6):801-808.
- Disease and Conditions: Gout. American College of Rheumatology. Accessed Dec. 7, 2017
- Disease Management: Gout and Calcium Pyrophosphate Deposition Disease. Cleveland Clinic Center for Continuing Education. Accessed Dec. 7, 2017.