Top 10 Rare Diseases

While conditions like cancer and HIV are widely known, have you ever come across Alpha-1 Antitrypsin Deficiency or Dercum’s disease?

Beyond the well-known illnesses that impact us or those close to us, and often receive media or charitable focus, there exists a myriad of other health threats. Whether caused by a virus or a genetic anomaly, these conditions share a common trait: they are far from pleasant.

We will explore the top 10 rare diseases, some of which might be unfamiliar to you, while others are conditions you’d hope to never encounter again.

Descriptions of these diseases are provided by the National Organization for Rare Disorders (NORD). To explore their comprehensive Rare Disease Database, which includes contact details for related organizations, visit their website at www.rarediseases.org.

1: Progressive Multifocal Leukoencephalopathy (PML)

Progressive multifocal leukoencephalopathy (PML) is a rare neurological condition that damages the myelin, a protective layer around nerve cells in the brain and spinal cord, also referred to as the central nervous system's white matter. It is triggered by the JC virus (JCV), named after the patient in whom it was first identified. This virus is highly prevalent, present in about 85% of adults globally. It remains dormant in healthy individuals but becomes active when the immune system is severely compromised, such as in those with HIV/AIDS, blood cancers, or organ transplant recipients on immunosuppressive drugs. PML affects roughly one in 200,000 people.

The term "progressive" in PML indicates that the condition worsens over time, often resulting in significant brain damage. "Multifocal" refers to the virus affecting multiple areas of the brain, though some patients may have only a single lesion. "Leukoencephalopathy" signifies that the disease primarily impacts the brain's white matter or myelin, although rare cases may also involve gray matter neurons.

2: Paraneoplastic Neurologic Syndromes (PNS)

Paraneoplastic neurologic syndromes (PNS) are a collection of disorders impacting the nervous system—including the brain, spinal cord, nerves, and muscles—in individuals with cancer. The term "paraneoplastic" indicates that these neurological issues are not directly caused by the tumor but rather by the immune response triggered by the tumor. The body’s immune system mistakenly identifies the tumor as a threat, launching an attack using antibodies and lymphocytes. This immune reaction can inadvertently harm the nervous system, sometimes severely. In many cases, the nervous system damage caused by PNS can be more significant than the damage to the tumor itself. While some patients may experience complete recovery, others may suffer lasting effects.

3: Dercum's Disease

Dercum’s disease is an exceptionally rare condition marked by numerous painful fatty growths known as lipomas. These growths typically appear beneath the skin on the torso, upper arms, and upper legs. The pain linked to Dercum’s disease can be intense, often resulting from the growths pressing on nearby nerves. It primarily affects adults, with a higher prevalence in women. Symptoms may also include weight gain, depression, fatigue, and confusion. The exact cause of Dercum’s disease remains unknown.

4: Familial Idiopathic Basal Ganglia Calcifications (Fahr's Disease)

Fahr's Disease is a rare neurological disorder involving abnormal calcium deposits and cell loss in specific brain regions, such as the basal ganglia. Often termed idiopathic basal ganglia calcification (IBGC), its cause remains unclear. Symptoms include cognitive decline, motor skill loss, and eventual paralysis accompanied by muscle rigidity and restricted movement. Additional signs may include involuntary writhing (athetosis) or jerky movements (chorea). Some patients may experience optic atrophy, leading to partial or complete vision loss.

Medical literature indicates that Fahr's Disease often runs in families. It can be inherited as an autosomal recessive or dominant trait, though it may also occur sporadically without a clear cause. Some experts propose that it could result from an unidentified infection during pregnancy affecting fetal development.

5: Neuromyelitis Optica (Devic's disease)

Neuromyelitis optica, or Devic disease (DD), is a chronic nerve tissue disorder marked by inflammation of the optic nerve (optic neuritis) and spinal cord (myelitis). It manifests in two forms. The less common, classical type involves a series of attacks over a short period, with few recurrences after the initial episode. The more common form features repeated attacks with periods of remission in between, which can last weeks, months, or years. Early stages of Devic disease are often mistaken for multiple sclerosis.

6: Tardive Dyskinesia

Tardive Dyskinesia (TD) is a neurological movement disorder caused by prolonged use of dopamine receptor-blocking medications, often prescribed for psychiatric or gastrointestinal conditions. These drugs can lead to biochemical changes in the brain's striatum. The exact reason why some individuals develop TD while others do not remains unclear. A more severe variant, tardive dystonia, involves slower, twisting movements of the neck and trunk muscles.

7: Landau Kleffner Syndrome

Landau Kleffner syndrome (LKS) involves the loss of language comprehension and expression (aphasia), accompanied by highly abnormal EEG readings that often lead to seizures.

8: Alpha-1-Antitrypsin Deficiency (A1AD)

Alpha-1 Antitrypsin Deficiency (A1AD) is an inherited condition marked by insufficient levels of the alpha-1 antitrypsin (A1AT) protein in the blood. This deficiency increases the risk of various diseases, most notably emphysema, and less commonly liver disease or a rare skin condition called panniculitis. The lack of A1AT allows protein-breaking enzymes to damage tissues, leading to lung destruction (emphysema) and potential liver and skin issues. Normally, A1AT is released by neutrophils during infections or inflammation. Its deficiency causes unchecked protein breakdown, particularly in lung tissues, accelerating emphysema, especially with smoking or certain occupational exposures.

9: Cyclic Vomiting Syndrome (CVS)

Cyclic vomiting syndrome (CVS) is a rare disorder defined by recurring bouts of severe nausea and vomiting. Episodes can last from hours to days, followed by symptom-free periods. This alternating pattern sets CVS apart from similar conditions. The nausea and vomiting can be debilitating, often leaving individuals bedridden. Additional symptoms during episodes include paleness, lethargy, abdominal pain, and headaches. Some children may outgrow CVS but develop migraines later. CVS is more common in children, though adults experience fewer but longer episodes. The exact cause remains unknown.

10: Spinal Muscular Atrophy (SMA)

Spinal muscular atrophy (SMA) encompasses a group of genetic disorders marked by the degeneration of motor neurons. These neurons relay signals from the brain or spinal cord to muscles or glands. Their loss results in progressive weakness and atrophy, particularly in proximal muscles like those in the shoulders, hips, and back, which are essential for crawling, walking, sitting, and head control. Severe SMA types can impair muscles involved in breathing, swallowing, and feeding.

SMA is categorized into subtypes based on symptom severity and age of onset. Types 0, I, II, III, and IV are autosomal recessive disorders linked to mutations in the SMN1 and SMN2 genes. Finkel type SMA, however, is autosomal dominant and associated with mutations in the VAPB gene.