Tuesday, January 10, 2012

The rarest human diseases

When faced with discussing the rarest disease, one must contemplate a number of factors. Where? What kind of disease? In which century? And rarity can only be qualified relative to the "common" diseases. Here, we discuss both ends of the spectrum

Defining disease

Disease generally refers to infectious disease, but it may also include chronic disease, genetic disorders, and pathologies such as cancer. How common a disease is (i.e., the prevalence) may vary by geography, gender, age group, and environmental or hereditary factors.


Difference national health agencies define a rare disease differently, but the National Institutes of Health in the United States currently defines “rare disease” as one affecting less than 200,000 Americans. The agency estimates that there are approximately 7,000 rare diseases affecting 25 million Americans. The rarest diseases tend to be genetic in nature because of their inability to spread among the population outside of reproduction, though acquired neurological conditions are also often rare.

Diseases affecting a few - the rare diseases 

Pinpointing the rarest diseases in the world is a tough task as it implies that the disease occurs often enough to be known and recorded, but so rarely that other diseases easily outshine it in reports. 



The rarest disease is likely one that is already eradicated. The last known natural case of smallpox was recorded in Somalia in 1977. Prior to that time it ravaged the human population, killing roughly a third of all it infected. The virus that causes the disease now only exists as laboratory samples.

Smallpox presentation, Wellcome Collection

Fields condition 

In 1998, 4-year-old Welsh twins Catherine and Kirstie Fields began showing the symptoms of a deteriorating muscular disease that stumped doctors. The neuromuscular condition was so rare that doctors were certain they are the only people in the world who have it and named it after them – Fields condition or Fields’ disease.


Hutchinson-Gilford Progeria Syndrome, known simply as progeria, is a condition in which a child prematurely ages. First described in the late 1800s, the disease has been reported across the globe but only affects 1 in 4 million to 1 in 8 million children. Individuals with the condition rarely make it to the second decade of life. The disease is currently thought to be a defect in genes encoding lamins, cytoskeletal proteins involved in a number of cellular processes and tissues, coinciding with the systemic symptoms and problems encountered in these patients.

Human prion diseases 

Among the infectious diseases, prion diseases are among the most rare. The pathogens in these diseases are proteins that undergo a conformational change and disrupt the working structure of the brain. Because they are transmissible, they can cause an acquired neurological disease, though some variants may be due to genetic abnormalities. Among the human forms of prion diseases are Creutzfeldt-Jakob disease and Kuru. Kuru is transmitted via cannibalism, specifically by the Fore people of New Guinea. The practice was halted in 1960, leaving very few carriers of the disease and no new transmission events into the 21st century. However, the long incubation period of Kuru leaves the chance for new manifestations among remaining carriers, the number of which is unknown. In contrast, Creutzfeldt-Jakob is thought to possibly be genetic (classical CJD, occurring in an estimated 1 out of every 1 million people) or related to mad cow disease (variant CJD, diagnosed in less than 200 people worldwide, none in the United States).


Scrapie prions in mouse neural cells, NIAID

Fibrodysplasia ossificans progressive 

Affecting an estimated 1 in 2 million people worldwide, fibrodysplasia ossificans progressive (FOP) has only been diagnosed in a few hundred people. The disorder involves the ossification of connective tissue – the ligaments and tendons are transformed into bone as the person ages. The most characteristic features are a large big toe and the shoulders and neck slumping into the upper torso in late childhood. The condition is thought to be the result of autosomal dominant mutations in the ACVR1 gene.

Moebius syndrome 

A sporadic genetic condition affecting the cranial nerves, particularly the sixth and seventh, Moebius syndrome results in facial deformities that are present at birth. Skeletal anomalies are also often seen and about a third of children with the disorder have autism. Only 300 cases have been described in the English literature according to Medscape, and about 2000 cases are thought to exist currently worldwide, affecting approximately 1 in 50,000 births.


Porphyria is a group of disorders in the production of heme, the protein in red blood cells that bind oxygen for transport. As a result, sufferers have pale skin, anemia, and historical comparisons to vampires, in addition to potential neurological issues. However, many people with the genetic mutations underlying the disorder do not exhibit symptoms. The National Institutes of Health Genetics Home Reference estimates the prevalence as 1 in 500 to 1 in 50,000. Like so many other rare diseases, the real prevalence of the disorder uncertain.

Most common infectious diseases

According to the World Health Organization’s 2009 World Health Statistics, 3 out of every 10 deaths is due to a communicable (or infectious) disease. Infectious diseases are more common in developing parts of the world, but they don’t recognize borders.


The prevalence of AIDS is highest in Africa, but the disease, which is caused by infection with human immunodeficiency virus (HIV) is found worldwide, affecting more than 30 million people. According to the WHO, in 2007, AIDS had a cause-specific mortality rate of 1049 per 100,000 population, five-times the rate of malaria.


Malaria is caused by infection with a parasite carried by mosquitoes. The Centers for Disease Control (CDC) estimates that 219 million people were infected in 2010, leading to more than 660,000 deaths, most of them in Africa. Programs aimed at eradicating mosquitoes in the mid-20th century led to the declaration of the United States as being malaria-free in 1949.


Tuberculosis is a respiratory infection with Mycobacterium tuberculosis. This disease was once the leading cause of death in the United States. According to the WHO, the disease has seen a resurgence in recent years in Europe and Africa, despite better treatments, and likely due to the increased longevity of HIV patients. The bacterium damages the lungs and other organs, leading to more than 1 million deaths worldwide each year according to the WHO.


The tuberculosis bacterium under a scanning electron microscope, CDC


Most common genetic diseases

Genetic diseases are caused by mutations in a person’s DNA. The mutations may be in genes or due to chromosomal abnormalities. Genetic Alliance UK estimates that 5.5% of the population will find that they have a genetic disorder by the time they are 25 years old. The most common genetic diseases are inherited in an autosomal dominant pattern, but autosomal recessive and X-linked genetic disorders also affect the population worldwide.

Familial combined hyperlipidemia and familial hypercholesterolemia are two autosomal dominant disorders that result in excess fatty substances accumulating in the blood (lipids in the first and cholesterol in the second). They occur in 5 and 2 out of every 1000 births, respectively. They result in atherosclerosis and heart disease.

The most common autosomal recessive genetic disorder is cystic fibrosis, which affects 0.4 per 1000 births according to Genetic Alliance UK, which amounts to 70,000 children and adults worldwide according to the Cystic Fibrosis Foundation. Cystic fibrosis affects the pancreas and lungs, leading to fluid accumulation in the respiratory system and breathing and digestion problems.

Finally, according to Genetics Alliance UK, the most common X-linked genetic disorder is Fragile X syndrome. This genetic abnormality affects males more than females and leads to cognitive decline and developmental issues. According to the National Library of Medicine, Fragile X affects 1 in 4000 males and 1 in 8000 females.

Most common non-communicable diseases

According to the WHO’s report, non-communicable diseases are responsible for more deaths than any other form of disease, and the CDC cites chronic disease as the most common cause of mortality among American (7 out of every 10 deaths). Half of these deaths are due to heart disease, cancer and stroke.

Heart disease 

The term “heart disease” generally refers to coronary artery disease. This is a blockage of the arteries that feed the heart, leading to a heart attack. The CDC estimates that heart disease kills 600,000 people in the United States each year, and 715,000 Americans have a heart attack each year.


Stroke is similar to heart disease, but it is a blockage of the arteries feeding the brain. The National Stroke Association cites stroke as the fourth leading cause of death and disability in the United States, with more than three-quarters of a million strokes occurring each year, and more than 7 million stroke survivors over the age of 20 years living in the United States.


The most common type of cancer and leading cause of cancer death varies by year and/or decade. Lung cancer is generally the most common cause of cancer death, but colorectal, breast, and prostate cancer account for the most cases. Cancer affects hundreds of thousands of Americans each year.

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