This condition is very rare, only affecting one in two million people. It is more common in females than in males. There are several hundred cases in the United States, 25 known cases in the United Kingdom, and less than that in Australia and New Zealand.

Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).

40 cases were diagnosed in northern Italy between 1940 and 1990. The gene frequency for this autosomal recessive condition was estimated at 1 in 218. In 1989, 16 cases on EOCA were diagnosed in children with a mean onset age of 7.1 In 1990, 20 patients affected by EOCA were studied. It was found that the ataxia of this study's participants affected the pyramidal tracts and peripheral nerves.

There is currently no effective treatment or cure for PSP, although some of the symptoms can respond to nonspecific measures. The average age at symptoms onset is 63 and survival from onset averages 7 years with a wide variance. Pneumonia is a frequent cause of death.

Surgery, such as the denervation of selected muscles, may also provide some relief; however, the destruction of nerves in the limbs or brain is not reversible and should be considered only in the most extreme cases. Recently, the procedure of deep brain stimulation (DBS) has proven successful in a number of cases of severe generalised dystonia. DBS as treatment for medication-refractory dystonia, on the other hand, may increase the risk of suicide in patients. However, reference data of patients without DBS therapy are lacking.

The cause of PSP is unknown. Fewer than 1% of those with PSP have a family member with the same disorder. A variant in the gene for tau protein called the H1 haplotype, located on chromosome 17, has been linked to PSP. Nearly all people with PSP received a copy of that variant from each parent, but this is true of about two-thirds of the general population. Therefore, the H1 haplotype appears to be necessary but not sufficient to cause PSP. Other genes, as well as environmental toxins, are being investigated as other possible contributors to the cause of PSP.

Survival rates for those diagnosed with typical PKAN is 11.18 years with a standard deviation of 7.8 years.

Several gene mutations have been identified in patients with camptocormia. These include the RYR1 gene in axial myopathy, the DMPK gene in myotonic dystrophy, and genes related to dysferlinopathy and Parkinson’s disease. These genes could serve as targets for gene therapy to treat the condition in the years to come.

A multitude of neurological disorders cause BSS, including motor neuron disease, CNS disorders, and early amyotrophic lateral sclerosis. Usually, the bent spine is caused by dysfunctioning extensor spinal muscles with a neurological cause.

Neurological origin BSS may also result from damage to the basal ganglia nuclei that are a part of the cerebral cortex, which play a major role in bodily positioning. Damage to this part of the brain can inhibit proper flexion and extension in the muscles necessary for maintaining an upright position. Additionally, the neurotransmitter dopamine plays a key role in the operation of basal ganglia. An abnormally low dopamine concentration, such as that associated with Parkinson’s disease, causes dysfunction in the basal ganglia and the associated muscle groups, leading to BSS. Studies have estimated the prevalence of BSS in people affected by Parkinson's to be between 3% and 18%.

Harding ataxia, also known as Early onset cerebellar ataxia with retained reflexes (EOCARR), is an autosomal recessive cerebellar ataxia originally described by Harding in 1981. This form of cerebellar ataxia is similar to Friedreich ataxia including that it results in poor reflexes and balance, but differs in several ways, including the absence of diabetes mellitus, optic atrophy, cardiomyopathy, skeletal abnormalities, and the fact that tendon reflexes in the arms and knees remain intact. This form of ataxia is characterized by onset in the first 20 years, and is less severe than Friedreich ataxia. Additional cases were diagnosed in 1989, 1990, 1991, and 1998.

Toxic optic neuropathy refers to the ingestion of a toxin or an adverse drug reaction that results in vision loss from optic nerve damage. Patients may report either a sudden loss of vision in both eyes, in the setting of an acute intoxication, or an insidious asymmetric loss of vision from an adverse drug reaction. The most important aspect of treatment is recognition and drug withdrawal.

Among the many causes of TON, the top 10 toxins include:

- Medications

- Ethambutol, rifampin, isoniazid, streptomycin (tuberculosis treatment)

- Linezolid (taken for bacterial infections, including pneumonia)

- Chloramphenicol (taken for serious infections not helped by other antibiotics)

- Isoretinoin (taken for severe acne that fails to respond to other treatments)

- Ciclosporin (widely used immunosuppressant)

- Acute Toxins

- Methanol (component of some moonshine, and some cleaning products)

- Ethylene glycol (present in anti-freeze and hydraulic brake fluid)

Metabolic disorders may also cause this version of disease. Systemic problems such as diabetes mellitus, kidney failure, and thyroid disease can cause optic neuropathy, which is likely through buildup of toxic substances within the body. In most cases, the cause of the toxic neuropathy impairs the tissue’s vascular supply or metabolism. It remains unknown as to why certain agents are toxic to the optic nerve while others are not and why particularly the papillomacular bundle gets affected.

Behr syndrome is characterized by the association of early-onset optic atrophy with spinocerebellar degeneration resulting in ataxia, pyramidal signs, peripheral neuropathy and developmental delay.

Although it is an autosomal recessive disorder, heterozygotes may still manifest much attenuated symptoms. Autosomal dominant inheritance also being reported in a family. Recently a variant of OPA1 mutation with phenotypic presentation like Behr syndrome is also described. Some reported cases have been found to carry mutations in the OPA1, OPA3 or C12ORF65 genes which are known causes of pure optic atrophy or optic atrophy complicated by movement disorder.

Many other neurological conditions are associated with acanthocytosis but are not considered 'core' acanthocytosis syndromes. The commonest are:

- Pantothenate kinase-associated neurodegeneration, an autosomal recessive condition caused by mutations in "PANK2".

- Huntington's disease-like syndrome type 2, an autosomal dominant condition caused by mutations in "JPH3" that closely resembles Huntington's disease.

- Bassen-Kornzweig disease, or Bassen-Kornzweig Syndrome (see also History).

- Levine-Critchley syndrome (see History).

- Paroxysmal movement disorders associated with GLUT1 mutations.

- Familial acanthocytosis with paroxysmal exertion-induced dyskinesias and epilepsy (FAPED).

- Some cases of mitochondrial disease.

There are very few reported cases of PED, there are approximately 20 reported sporadic cases of PED and 9 PED families but there is some dispute on the exact number of cases. In addition it appears that PED becomes less severe with aging. Prior to onset of a PED episode some patients reported onset of symptoms including sweating, pallor, and hyperventilation. In brain scans it was observed that patients suffering form frequent PEDs there was increased metabolism in the putamen of the brain and decreased metabolism in the frontal lobe. Another study using subtraction single photon emission computed tomographic (SPECT) imaging technique which was coregistered with an MRI on a patient presented with PED symptoms showed increased cerebral perfusion in the primary somatosensory cortex area, and a mild increase in the region of the primary motor cortex and cerebellum. While all these correlations are not fully understand as to what exactly is happening in the brain it provides areas of interest to study further to hopefully understand PED more fully.

Prevalence data regarding this disorder remains incomplete, however it is estimated that anywhere between 1 in 1,000,000 to 3 in 1,000,000 individuals will be afflicted with this disorder (based upon observed cases in a population), but once again this is only an estimate as the disease is so rare it is difficult to statistically and accurately ascertain.

TAA is an old term for a constellation of elements that can lead to a mitochondrial optic neuropathy. The classic patient is a man with a history of heavy alcohol and tobacco consumption. Respectively, this combines nutritional mitochondrial impairment, from vitamin deficiencies (folate and B-12) classically seen in alcoholics, with tobacco-derived products, such as cyanide and ROS. It has been suggested that the additive effect of the cyanide toxicity, ROS, and deficiencies of thiamine, riboflavin, pyridoxine, and b12 result in TAA.

Infantile neuroaxonal dystrophy is a rare pervasive developmental disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Eventually they lose previously acquired skills.

Athetosis is a commonly occurring symptom in the disease cerebral palsy. Of all people with the disease, between 16% and 25% of them actually exhibit the symptom of athetosis. A component of this is the finding that most often the symptoms that involve athetosis occur as a part of choreoathetosis as opposed to athetosis alone.

It is also noteworthy that the presence of athetosis in cerebral palsy (as well as other conditions) causes a significant increase in a person’s basal resting metabolic rate. It has been observed that those who have cerebral palsy with athetosis require approximately 500 more Calories per day than their non-cerebral palsy non-athetoid counterpart.

In examining the causes of hemiballismus, it is important to remember that this disorder is extremely rare. While hemiballismus can result from the following list, just because a patient suffers from one of these disorders does not mean they will also suffer from hemiballismus.

Stroke

Hemisballismus as a result of stroke occurs in only about 0.45 cases per hundred thousand stroke victims. Even at such a small rate, stroke is by far the most common cause of hemiballismus. A stroke causes tissue to die due to a lack of oxygen resulting from an impaired blood supply. In the basal ganglia, this can result in the death of tissue that helps to control movement. As a result, the brain is left with damaged tissue that sends damaged signals to the skeletal muscles in the body. The result is occasionally a patient with hemiballismus.

Traumatic Brain Injury

Hemiballismus can also occur as a result of a traumatic brain injury. There are cases in which victims of assault or other forms of violence have developed hemiballismus. Through these acts of violence, the victim’s brain has been damaged and the hemiballistic movements have developed.

Amyotrophic Lateral Sclerosis

This disease causes neuronal loss and gliosis, which can include the subthalamic nucleus and other areas of the brain. Essentially any disorder that causes some form of neuronal loss or gliosis in the basal ganglia has the potential to cause hemiballismus.

Nonketotic Hyperglycemia

Patients with nonketotic hyperglycemia can develop hemiballismus as a complication to the disease through the development of a subthalamic nucleus lesion. This is the second most common reported cause of hemiballismus. It can be found primarily in the elderly and many of the reported cases have come from East Asian origin, which suggests that there may be some genetic disposition to development of hemiballismus as a result of hyperglycemia. Hemiballistic movements appear when blood glucose levels get too high and then subside once glucose levels return to normal. This time scale for this is usually several hours. In patients with this type of hemiballismus, imaging reveals abnormalities in the putamen contralateral to the movements as well as the globus pallidus and caudate nucleus. While the hyperglycemia itself is not the cause of the hemiballistic movements, it has been suggested that petechial hemorrhage or a decreased production of GABA and acetylcholine could result secondary to the hyperglycemia. One of these issues could be responsible for the hemiballistic movements.

Neoplasms

A neoplasm is an abnormal growth of cells. Cases have shown that if this occurs somewhere in the basal ganglia, hemiballismus can result.

Vascular malformations

Vascular malformations can cause abnormal blood flow to areas of the brain. If too little blood is delivered to the basal ganglia, a stroke can occur.

Tuberculomas

This is another form of tumor that can result in the brain as a result of a tuberculous meningitis infection. This type of tumor can also damage parts of the basal ganglia, sometimes resulting in hemiballismus.

Demyelinating plaques

Demyelinating plaques attack the myelin sheaths on neurons. This decreases the conduction velocity of the neurons, making the signals received by the basal ganglia garbled and incomplete. This disorganized signal can also cause the chaotic movements characterized by hemiballismus.

Complications from HIV infection

Patients with HIV often have complications that arise along with AIDS. Hypoglycemia due to pentamidine use in patients with AIDS has been known to cause hemiballismus. In some patients, hemiballismus has been the only visible symptom to alert the physician that the patients may have AIDS. It is typically a result of a secondary infection that occurs due to the compromised immune system and the most common infection causing hemiballismus is cerebral toxoplasmosis. Most of the lesions that result from this infection are found in the basal ganglia. As long as the diagnosis is not missed, this type of hemiballismus can be treated just as well as in patients without HIV.

Chorea is another condition which results from damage to the basal ganglia. Similar to athetosis, it results from mutations affecting the pallidum inhibition of the thalamus as well as increased dopaminergic activity at the level of the striatum. Considering the etiology of both disorders are fairly similar, it comes as no surprise that chorea and athetosis can and usually do occur together in a condition called choreoathetosis.

In most cases, PED is familial, but can also be sporadic. In familial cases, pedigrees examined have shown PED to be an autosomal-dominant inheritance trait. PED also has been associated with Parkinson's disease, epilepsy and migraines, although the exact relationship between these is unknown.

A suspected contributor to familial PED is a mutation in the GLUT1 gene, SLC2A1, which codes for the transporter GLUT1, a protein responsible for glucose entry across the blood–brain barrier. It is not thought that the mutation causes a complete loss of function of the protein but rather only slightly reduces the transporter's activity. In a study of PED patients, a median CSF/blood glucose ratio of .52 compared to a normal .60 was found. In addition, reduced glucose uptake by mutated transporters compared with wild-type in Xenopus oocytes confirmed a pathogenic role of these mutations.

Another recent study was performed to continue to look at the possible connection between PED and mutations on the SLC2A1 gene which codes for the GLUT1 transporter. While PED can occur in isolation it was also noted that it occurs in association with epilepsy as well. In this study the genetics of a five-generation family with history of PED and epilepsy were evaluated. From the results it was noted that most of the mutations were due to frameshift and missense mutations. When looking at homologous GLUT1 transporters in other species it was noted that serine (position 95), valine (position 140), and asparagine (position 317) were highly conserved and therefore mutations in these residues would most likely be pathogenic. Therefore, these are areas of interest when looking at what could lead to PED.All mutations that were observed appeared to only affect the ability of GLUT1 to transport glucose and not the ability for it to be inserted in the membrane. The observed maximum transport velocity of glucose was reduced anywhere from 3 to 10 fold.

A study was performed to determine if the mutation known for the PNKD locus on chromosome 2q33-35 was the cause of PED. In addition, other loci were observed such as the familial hemiplegic migraine (FHM) locus on chromosome 19p, or the familial infantile convulsions and paroxysmal choreoathetosis (ICCA). All three of these suspected regions were found to not contain any mutations, and were therefore ruled out as possible candidates for a cause of PED.

Clinical presentation of CBD usually does not occur until age 60, with the earliest recorded diagnosis and subsequent postmortem verification being age 28. Although men and women present with the disease, some analysis has shown a predominant appearance of CBD in women. Current calculations suggest that the prevalence of CBD is approximately 4.9 to 7.3 per 100,000 people. The prognosis for an individual diagnosed with CBD is death within approximately eight years, although some patients have been diagnosed over 17 years ago (2017) and are still in relatively good standing, but with serious debilitation such as dysphagia, and overall limb rigidity. The partial (or total) use of a feeding tube may be necessary and will help prevent aspiration pneumonia, primary cause of death in CBD. Incontinence is common, as patients often can't express their need to go, due to eventual loss of speech. Therefore, proper hygiene is mandatory to prevent urinary tract infections.

McLeod syndrome is an X-linked recessive disorder caused by mutations in the "XK" gene encoding the Kx blood type antigen, one of the Kell antigens.

Like the other neuroacanthocytosis syndromes, McLeod syndrome causes movement disorder, cognitive impairment and psychiatric symptoms. The particular features of McLeod syndrome are heart problems such as arrhythmia and dilated cardiomyopathy (enlarged heart).

McLeod syndrome is very rare. There are approximately 150 cases of McLeod syndrome worldwide. Because of its X-linked mode of inheritance, it is much more prevalent in males.

Chorea can also be a manifestation of drug toxicity (for example, anticonvulsants, antiparkinson agents, neuroleptics, steroids, and estrogen), or a result of an infectious disease such as meningovascular syphilis, Lyme disease, viral encephalitis, and many others.

Onset : Early childhood

Progression: Chronic progressive

Clinical: Cerebellar ataxia plus syndrome / Optic Atrophy Plus Syndrome

Ocular: Optic atrophy, nystagmus, scotoma, and bilateral retrobulbar neuritis.

Other: Mental retardation, myoclonic epilepsy, spasticity, and posterior column sensory loss. Tremor in some cases.

Musculoskeletal

Contractures, lower limbs, Achilles tendon contractures, Hamstring contractures, Adductor longus contractures

Systemic

Hypogonadotrophic hypogonadism.