Skip to main content

The Top 10 Rarest Diseases

Larry Slawson received his Master's Degree from UNC Charlotte in 2018. He has a keen interest in epidemiology.

From Kuru to Fields' Disease, this article ranks the 10 rarest diseases known to currently exist worldwide.

From Kuru to Fields' Disease, this article ranks the 10 rarest diseases known to currently exist worldwide.

What Is the World's Rarest Disease?

Throughout the world, a number of rare diseases are known to afflict the human population at large. According to the National Institutes of Health (NIH), it is currently estimated that more than 7,000 different rare diseases have been identified by researchers over the course of human history. As of March 2022, approximately 300 million people (worldwide) suffer from one or more of these health issues, with 25 to 30 million of these people coming from the United States alone. From Kuru to Fields’ Disease, this work ranks the 10 rarest diseases known to currently exist worldwide. Included is a brief overview of each disease, its symptoms, prognosis, and various treatment options. It is the author’s hope that a better understanding (and appreciation) of these rare diseases will accompany readers following their completion of this work.

Selection Criteria

In order to select the world’s rarest diseases, a number of criteria were necessary for the ranking process. First and foremost, each of the following diseases is ranked according to their overall prevalence worldwide. As the name of this work implies, those with the fewest occurrences among humans are ranked first, with greater transmission rates appearing in the higher echelons of our article. Finally, and crucially, it was important to only include diseases that have been confirmed in healthcare settings or research facilities and to exclude hypothetical cases of new diseases that remain unconfirmed by the scientific community. While these criteria present a number of potential shortcomings and gaps within the research process, the author believes them to be the best means for ranking (and identifying) the world’s rarest diseases.

What is a Rare Disease?

For the extents and purposes of this work, a “rare disease” implies any disorder (or condition) that afflicts fewer than 200,000 people a year in the United States or 1 in 2,000 individuals (when using the European Union criteria).

The World's Rarest Diseases Ranked

  • Morgellans Disease
  • Microcephaly
  • Parry-Romberg Syndrome
  • Kuru
  • Epidermodysplasia Verruciformis
  • Methemoglobinemia
  • Fibrodysplasia Ossificans Progressiva (Stoneman's Disease)
  • Hutchinson-Gilford Progeria Syndrome (HGPS)
  • RPI Deficiency
  • Fields’ Disease
Morgellons Disease.

Morgellons Disease.

10. Morgellons Disease

  • Number of Cases: 300,000
  • First Discovered: 2002
  • Overall Survival Rate: Unknown

Morgellons disease refers to an extremely rare (and poorly understood) condition that involves small fibers and particles that emerge from various skin sores. The disease is extremely controversial amongst the medical community, as some doctors believe it to be a “delusional infestation” that is a result of psychotic processes, rather than an actual skin condition. As such, it is regularly classified as a mental health condition by many doctors, as no parasitic or bacterial causes have been identified by the medical community at this time. In regard to prevalence, fewer than 300,000 people are believed to suffer from Morgellons Disease, with the vast majority of these cases appearing in middle-aged white women.

Signs and Symptoms of Morgellons Disease

Among the most common symptoms reported by people with Morgellons disease is skin rashes (or sores) that cause intense itching. Other issues include a “crawling” sensation on (or under) the skin, that many compare to the feeling of insects moving across the skin. Fibrous and stringy material may also manifest itself on the skin with this condition, and is occasionally followed by fatigue. In more serious cases, cognitive impairment is common, and includes difficulty concentrating (brain fog), short-term memory loss, as well as severe depression.

Treatment of Morgellons Disease

In general, Morgellons Disease is known to dramatically decrease a person’s quality of life ( Unfortunately, no cure has been developed for the disease as it is poorly understood by the medical community. Likewise, no specific treatment option has been approved for the disease, as dermatological studies have yielded conflicting results on specific techniques that are useful for intervention. As such, many have turned to holistic approaches to treating the disease, including cognitive behavioral therapy, antibiotic therapy, and various topical ointments. Fortunately, the disease is incredibly rare, occurring in only 3.65 per 100,000 people worldwide.



9. Microcephaly

  • Number of Cases: Unknown
  • First Discovered: 2002
  • Overall Survival Rate: Unknown

Microcephaly refers to an incredibly rare neurological condition that affects an infant’s head. Occasionally detected at birth, the disorder prevents the child’s head from properly developing (growing) as it should in the days, weeks, and years that follow. As of March 2022, it is currently believed that microcephaly is caused by genetic and environmental factors. The Zika Virus, in particular, has recently been identified as a potential cause for the disorder, although more research is needed to determine if this is true.

Signs and Symptoms of Microcephaly

As of 2022, current symptoms of microcephaly are believed to include dwarfism, delayed speech and development, hyperactivity, seizures, convulsions, as well as impaired motor skills. Current survival rates are unknown for individuals with the disease. However, it is currently believed that the condition dramatically affects an individual’s life expectancy.

Treatment of Microcephaly

To date, no effective treatments have been established to combat microcephaly. Nevertheless, early detection of the disorder can allow for rapid intervention to occur, allowing supportive therapies (such as speech and occupational therapy) to begin which may help to enhance the child’s development and quality of life ( While this, in itself, will not cure the disease, the overall quality of life can be greatly improved for individuals suffering from this particular disorder.

Scroll to Continue

Read More From Youmemindbody

Parry-Romberg Syndrome.

Parry-Romberg Syndrome.

8. Parry-Romberg Syndrome

  • Number of Cases: Unknown
  • First Discovered: 1825
  • Overall Survival Rate: Unknown

Parry-Romberg Syndrome refers to an incredibly rare (and acquired) disorder that is generally characterized by a progressive atrophy of the skin and soft tissues of the facial region. In most cases, this disorder is centered primarily on one-half of an individual’s face; however, in some instances both sides are equally affected ( Parry-Romberg Syndrome usually presents itself within the first decade of a person’s life, and rarely manifests itself in adulthood. Following an atrophy phase of approximately 5 to 10 years, the disease typically concludes with a “burnout period” where no active disease occurs. To date, researchers are unsure what causes the disorder, as it appears to occur randomly and sporadically amongst the world’s population.

Signs and Symptoms of Parry-Romberg Syndrome

To date, symptoms of Parry-Romberg Syndrome vary significantly from one individual to another, with symptoms ranging from mild to severe. In general, however, the most common issue afflicting those with this disorder is a shrinking (atrophy) of the facial tissues. This includes fat, muscle, and occasionally the bone. Shrinkage can be mild (almost imperceptible to the naked eye), or can be significant for others, leading to visible asymmetry of the facial region. In more severe cases, headaches and seizures may also occur.

Treatment of Parry-Romberg Syndrome

To date, medical treatment (via oral and topical medication) have proven themselves to be unsuccessful against Parry-Romberg Syndrome. As such, surgery is often the main form of treatment for this disorder, and is typically utilized during the “burnout period” of the disease (to ensure that no additional atrophy occurs). Typical surgery involves “fat transfer” via injection processes, as well as the incorporation of dermal fillers. Soft tissue transfers may also be utilized by surgeons in order to provide optimal cosmetic results. Fortunately, the disease is incredibly rare, occurring in 1 out of 250,000 individuals, worldwide.

Papua New Guinea tribe affected by kuru.

Papua New Guinea tribe affected by kuru.

7. Kuru

  • Number of Cases: 2,700
  • First Discovered: 1957
  • Overall Survival Rate: 0% (No Cure)

Kuru is an extremely rare disease known to affect the central nervous system of its victims. First discovered in New Guinea, it is believed that the disease originated from cannibalistic practices in the region. As part of the Fore people’s funeral rituals, individuals would cook (and eat) the brains of dead people to symbolize their respect for loved ones. This gesture, in turn, lead to the transmission of Kuru disease as infectious proteins (known as prion) were ingested by family members and friends of the deceased (with deadly consequences).

Although these cannibalistic practices were officially halted in 1960 by government decree, signs of the disease continued to manifest itself for several more years as Kuru maintains a long incubation period that is difficult to spot in its early stages. Today, the disease is extraordinarily rare, with the last known cases occurring in 2005 and 2009, respectively.

Signs and Symptoms of Kuru Disease

Diagnosing Kuru disease is extremely difficult given its long incubation period (10 to 50 years). During this time, few symptoms present themselves with the exception of generalized issues that mimic common health issues. Once the disease takes control of the body, however, symptoms include coordination problems, difficulty with walking, severe pain in the extremities, as well as tremors, muscle jerks, migraine headaches, and difficulty swallowing. Death usually occurs within 1 to 2 years following the first sign of infection.

Due to its rarity, only a handful of medical studies have been performed on the disease in recent years. Nevertheless, it is believed that Kuru presents itself in three stages, with the third (final) being fatal in all known cases. In its final stages, individuals usually die within three months due to their inability to eat, or from secondary infections such as pneumonia.

Treatment of Kuru Disease

As of March 2022, no known treatment exists for Kuru disease. As a result, it is considered fatal in 100-percent of cases. Although a number of treatments were developed to counteract the progression of the disease after its discovery in 1957, death usually presented itself within 12 months (following the onset of symptoms). Fortunately, this is an incredibly rare (and virtually non-existent disease) in the modern era, and one that will likely be known only from a study of history.

Epidermodysplasia Verruciformis.

Epidermodysplasia Verruciformis.

6. Epidermodysplasia Verruciformis

  • Number of Cases: 600
  • First Discovered: 1922
  • Overall Survival Rate: 100% (Lifelong Condition)

Epidermodysplasia Verruciformis (also known as “EV”) is an extremely rare skin disease inherited from an individual’s parents. Manifesting itself during infancy and early childhood in the majority of cases, EV is characterized as a progressive disease that makes individuals highly-susceptible to infections caused by the human papillomavirus (HPV). Little is currently known or understood about its causes; however, it is theorized that the disorder is caused by the inheritance of two abnormal EV genes (one each from the mother and father). Once passed on to offspring, the victim’s immune response is greatly inhibited against HPV and its various subtypes (making infection likely). While the disease itself is not usually fatal, it is important to note that EV dramatically increases an individual’s risk of skin cancer. According to, approximately two-thirds of people with EV will develop skin cancer at some point of their life (

Signs and Symptoms of Epidermodysplasia Verruciformis

As of 2022, very little is known about Epidermodysplasia Verruciformis due to its rare occurrence. Nevertheless, the hallmark symptoms of EV involve wartlike lesions that cover parts of an individual’s body. Although symptoms can manifest at any age, half of all cases appear between the ages of 5 and 11 ( The lesions that present themselves may be flat-topped or bumpy in their overall appearance, or become small raised bumps (also known as papules). Large patches of reddish skin (known as plaques) and brown lesions resembling scabs may also be present. These patches may appear anywhere on the body, with the hands, feet, face, ears, neck, arms, and legs being the most common spots of growth.

Treatment of Epidermodysplasia Verruciformis

Currently, there is no cure for EV. Likewise, treatment options are designed solely for the purpose of alleviating symptoms and improving the quality of an individual’s life. Surgical options, for example, provide a temporary cosmetic solution, and involve a doctor scraping away a lesion through a procedure known as “curettage.” Chemical treatments, topical ointments, and cryotherapy may also be utilized to remove the lesions as well. Fortunately, EV is an exceptionally rare disease affecting only a handful of individuals worldwide. Since it was first discovered in 1922, only 600 cases have been reported, making it one of the world’s rarest diseases.



5. Methemoglobinemia

  • Number of Cases: 319
  • First Discovered: 1932
  • Overall Survival Rate: Unknown

Methemoglobinemia (also known as MetHb) refers to an extraordinarily rare blood disorder that results in an elevated number of methemoglobin (a form of hemoglobin) that is produced by the body. When this condition occurs, hemoglobin’s ability to carry (and distribute) oxygen to the body is severely impaired. Very little is known about the current causes of methemoglobinemia; however, it is currently hypothesized that the condition is inherited (congenital), and may also be caused by exposure to certain medications, foods, or chemicals. Inherited MetHb, on the other hand, results from red blood cells (RBCs) that lack an enzyme known as erythrocyte reductase, or when the enzyme doesn’t work properly in the body ( Without appropriate treatment, the condition is life-threatening in many cases.

Signs and Symptoms of Methemoglobinemia

Some individuals with MetHb have no symptoms at all, and may not require treatment. Individuals with more severe symptoms, however, will notice blueness around the mouth and extremities, along with extreme lethargy, excessive salivation, loss of consciousness, as well as vomiting and diarrhea. In “type 2” MetHb, developmental delays, seizures, and learning difficulties are also common. In cases where methemoglobin levels go above 70-percent, coma and death may occur.

Treatment of Methemoglobinemia

Following a diagnosis of Methemoglobinemia, standard treatment involves infusion of the drug methylene blue (which has been proven to help individuals recover quickly). For those that do no respond to this medication, however, a blood transfusion may also be necessary to remedy its effects on the body. Hereditary (type 1) methemoglobinemia may also be treated by aspirin therapy, as it has shown promising results as well. Fortunately, the disease is quite rare, with only 319 cases reported worldwide, and less than 100 new cases occurring each year.

Fibrodysplasia Ossificans Progressiva.

Fibrodysplasia Ossificans Progressiva.

4. Fibrodysplasia Ossificans Progressiva (FOP)

  • Number of Cases: <300
  • First Discovered: 2006
  • Overall Survival Rate: 0% (No Cure)

Fibrodysplasia Ossificans Progressiva (FOP) is an incredibly rare disease that is known to affect the muscular-skeletal system, as well as connective tissues of the body (such as tendons and ligaments). Also known as “stoneman’s disease,” the disorder causes the body’s connective tissues to be slowly replaced by bone, resulting in bone outside of the skeleton (also known as extra-skeletal or heterotopic bone). As the disease progresses, movement is greatly constrained, resulting in serious (debilitating) issues over time.

In terms of the disease’s frequency, it is currently estimated that only 1 in 2 million people are affected by FOP. As of March 2022, only 801 cases of the disorder are known to exist worldwide. Due to its rarity, very little is known about FOP’s causes and origins. However, some researchers have hypothesized that mutations in the ACVR1 gene may be to blame. This protein is found throughout much of the muscular-skeletal system, and gives instructions for making BMP type 1 receptors. Mutations are believed to disrupt these receptors, resulting in an overgrowth of bone and cartilage.

Signs and Symptoms of Fibrodysplasia Ossificans Progressiva (FOP) Disease:

Most individuals with Fibrodysplasia Ossificans Progressiva disease are diagnosed with the disorder before their 10th birthday. Among the most commonly cited symptoms are malformed thumbs and toes, restricted movement, restricted breathing (due to excessive bone growth in the chest), hearing impairment, as well as visible swelling throughout the body. Spinal rigidity, lumps under the skin, as well as progressive pain (and stiffness) are also among the most common symptoms of the disease, with death resulting from secondary infections and heart failure.

Treatment of FOP Disease

To date, no specific cure has been developed for Fibrodysplasia Ossificans Progressiva Disease. However, a number of treatment options exist to improve quality of life (as the disease’s progression cannot be delayed). These include corticosteroids to reduce painful inflammation and swelling, nonsteroidal anti-inflammatory drugs (NSAIDS), braces and specially-fitted shoes for improvement of mobility, as well as physical therapy.

Hutchinson-Gilford Progeria Syndrome.

Hutchinson-Gilford Progeria Syndrome.

3. Hutchinson-Gilford Progeria Syndrome (HGPS)

  • Number of Cases: 130
  • First Discovered: 1886
  • Overall Survival Rate: 0% (No Cure)

Hutchinson-Gilford Progeria Syndrome (HGPS) is a genetic condition that is characterized by the rapid onset of aging during childhood. Children with this disease often appear completely normal during birth and early childhood, but tend to grow at a slower rate than other kids. As the disease progresses, the child will begin to develop aged skin, prominent eyes, and a loss of fat under the skin (

Hutchinson-Gilford Progeria Syndrome is an extremely rare disease that presents itself in 1 out of every 4 million newborns worldwide. Since being discovered in 1886, only 130 cases have been systematically investigated in western society. To date, it remains unclear what causes this particular disease to develop. However, it is speculated that mutations in the LMNA gene may be responsible for HGPS. This is due to the fact that this particular gene is responsible for making a protein called “lamin A,” which plays a vital role in the development of nuclei within cells. With HGPS, abnormal lamin A proteins are created within the body, making the cell’s nuclear envelope unstable. In response, cells in the body tend to die off at a rapid rate leading to an uncontrollable progression of the disease.

Signs and Symptoms of Hutchinson-Gilford Progeria Syndrome (HGPS)

Symptoms of HGPS usually begin to present themselves during the newborn stage of development. Common symptoms include hardened skin over the buttocks, legs, and abdomen, as well as bluish discoloration of the skin and mucous membranes. By two years of age, the disease is far more evident, as slow growth and weight gain are among its most prominent features. As the disease progresses further along, prominent eyes, thin noses and lips, as well as small chins and protruding ears are among the hallmark symptoms of advanced HGPS. And while intellectual development is not affected by this syndrome, hardening of the arteries, loss of fat under the skin, and joint abnormalities are common. As arteriosclerosis begins to present itself in later stages, death by heart attack or stroke are among the most common causes of death for individuals.

Treatment for HGPS Disease

Sadly, no specific cure has been created for HGPS disease; however, a number of treatment options exist to slow its spread. These include oral medication, physical therapy, and a steady consumption of nutrient-rich foods/supplements. Thankfully, it is one of the rarest diseases in the world, and seldomly presents itself within children.

RPI Deficiency.

RPI Deficiency.

2. RPI Deficiency

  • Number of Cases: 4
  • First Discovered: 1999
  • Overall Survival Rate: Unknown

Ribose 5-phosphate Isomerase (RPI) deficiency refers to an incredibly rare disease that results in mutations of an enzyme within the pentose phosphate pathway of an individual. Believed to be a hereditary disorder, RPI deficiency is characterized by progressive leukoencephalopathy, resulting in high-levels of ribitol and D-arabitol levels within the victim’s brain and bodily fluids. As of 2022, only four individuals have been diagnosed with RPI Deficiency ever since its initial discovery. As a result, almost nothing is currently known about the disorder, leaving doctors to only speculate about its causes and specifics.

Signs and Symptoms of RPI Deficiency

Common symptoms of RPI Deficiency include optic atrophy, cerebellar ataxia, seizures, nystagmus, spasticity, difficulty speaking, leukoencephalopathy, as well as delays in growth. To date, no specific treatments have been developed to combat this disease, nor is there any specific prognosis on the impact of this condition on daily life. Overall life-expectancy is also not currently known by medical experts as it was only discovered a few decades ago (leaving researchers with little time to observe its effects on bodily systems). Fortunately, RPI deficiency is extraordinarily rare at this current time.

The Fields twins.

The Fields twins.

1. Fields' Disease

  • Number of Cases: 2
  • First Discovered: 1994
  • Overall Survival Rate: Unknown

Fields’ Disease is an exceptionally rare disease that is characterized by neuromuscular and muscular degeneration. The disease was first discovered in a pair of twins known as Kirstie and Catherine Fields (hence its name). As of 2022, the disease appears to be both congenital and progressive; however, very little is currently understood about its causes, progression, as well as its overall survivability. Likewise, no specific effects have been recorded about the disease in regard to cognitive and intellectual impairment at this time. For the time being, these two twins remain the only cases of Fields’ Disease to have been observed in the medical community and human history.

Signs and Symptoms of Fields’ Disease

Signs and symptoms of Fields’ Disease are still poorly understood due to the fact that only two individuals have ever been observed with the disorder. Nevertheless, it is currently believed that the disease is a neurodegenerative disorder that progresses slowly over time. The only observed symptoms (so far) have been a slow deterioration of muscles within the body, along with a disruption of an individual’s nerves (causing them to move involuntarily). To date, the overall probability of having this disease is believed to be 1 in 3.75 billion, making it the rarest disease ever discovered by the medical community. There is currently no approved treatment for the disorder, and it remains unknown if the disease is fatal.

Works Cited



  • Pixabay Commons.
  • Wikimedia Commons.

This content is accurate and true to the best of the author’s knowledge and is not meant to substitute for formal and individualized advice from a qualified professional.

© 2022 Larry Slawson

Related Articles