Patients with severe forms of MJD have a life expectancy of approximately 35 years. Those with mild forms have a normal life expectancy. The cause of death of those who die early is often aspiration pneumonia.

Exercise in middle age may reduce the risk of Parkinson's disease later in life. Caffeine also appears protective with a greater decrease in risk occurring with a larger intake of caffeinated beverages such as coffee. People who smoke cigarettes or use smokeless tobacco are less likely than non-smokers to develop PD, and the more they have used tobacco, the less likely they are to develop PD. It is not known what underlies this effect. Tobacco use may actually protect against PD, or it may be that an unknown factor both increases the risk of PD and causes an aversion to tobacco or makes it easier to quit using tobacco.

Antioxidants, such as vitamins C and E, have been proposed to protect against the disease, but results of studies have been contradictory and no positive effect has been proven. The results regarding fat and fatty acids have been contradictory, with various studies reporting protective effects, risk-increasing effects or no effects. There have been preliminary indications that the use of anti-inflammatory drugs and calcium channel blockers may be protective. A 2010 meta-analysis found that nonsteroidal anti-inflammatory drugs (apart from aspirin), have been associated with at least a 15 percent (higher in long-term and regular users) reduction of incidence of the development of Parkinson's disease.

An average clinical profile from published studies shows that the median onset age for HDLS patients is 44.3 years with a mean disease duration of 5.8 years and mean age of death at 53.2 years. As of 2012, there have been around 15 cases identified with at least 11 sporadic cases of HDLS. HDLS cases have been located in Germany, Norway, Sweden, and the United States, showing an international distribution focusing between Northern Europe and the United States.

Through the study of numerous kindred, it was found that the disease did not occur among just males or females, but rather was evenly distributed indicative of an autosomal rather than a sex-linked genetic disorder. It was also observed that the HDLS cases did not skip generations as it would occur with a recessive inheritance, and as such has been labeled autosomal dominant.

PD invariably progresses with time. A severity rating method known as the Unified Parkinson's disease rating scale (UPDRS) is the most commonly used metric for clinical study. A modified version known as the MDS-UPDRS is also sometimes used. An older scaling method known as the Hoehn and Yahr scale (originally published in 1967), and a similar scale known as the Modified Hoehn and Yahr scale, have also been commonly used. The Hoehn and Yahr scale defines five basic stages of progression.

Motor symptoms, if not treated, advance aggressively in the early stages of the disease and more slowly later. Untreated, individuals are expected to lose independent ambulation after an average of eight years and be bedridden after ten years. However, it is uncommon to find untreated people nowadays. Medication has improved the prognosis of motor symptoms, while at the same time it is a new source of disability, because of the undesired effects of levodopa after years of use. In people taking levodopa, the progression time of symptoms to a stage of high dependency from caregivers may be over 15 years. However, it is hard to predict what course the disease will take for a given individual. Age is the best predictor of disease progression. The rate of motor decline is greater in those with less impairment at the time of diagnosis, while cognitive impairment is more frequent in those who are over 70 years of age at symptom onset.

Since current therapies improve motor symptoms, disability at present is mainly related to non-motor features of the disease. Nevertheless, the relationship between disease progression and disability is not linear. Disability is initially related to motor symptoms. As the disease advances, disability is more related to motor symptoms that do not respond adequately to medication, such as swallowing/speech difficulties, and gait/balance problems; and also to levodopa-induced complications, which appear in up to 50% of individuals after 5 years of levodopa usage. Finally, after ten years most people with the disease have autonomic disturbances, sleep problems, mood alterations and cognitive decline. All of these symptoms, especially cognitive decline, greatly increase disability.

The life expectancy of people with PD is reduced. Mortality ratios are around twice those of unaffected people. Cognitive decline and dementia, old age at onset, a more advanced disease state and presence of swallowing problems are all mortality risk factors. On the other hand, a disease pattern mainly characterized by tremor as opposed to rigidity predicts an improved survival. Death from aspiration pneumonia is twice as common in individuals with PD as in the healthy population.

In 2013 PD resulted in about 103,000 deaths globally, up from 44,000 deaths in 1990. The death rate increased from an average of 1.5 to 1.8 per 100,000 during that time.

The rate of MSA is estimated at 4.6 cases per 100,000 people. This disease is more common in men than in women, with studies showing ratios ranging from between 1.4:1 to ratios as high as 1.9:1. Chef Kerry Simon died from complications of MSA.

MSA usually progresses more quickly than Parkinson's disease. There is no remission from the disease. The average remaining lifespan after the onset of symptoms in patients with MSA is 7.9 years. Almost 80% of patients are disabled within five years of onset of the motor symptoms, and only 20% survive past 12 years. Rate of progression differs in every case and speed of decline may vary widely in individual patients.

O’Sullivan and colleagues (2008) identified early autonomic dysfunction to be the most important early clinical prognostic feature regarding survival in MSA. Patients with concomitant motor and autonomic dysfunction within three years of symptom onset had a shorter survival duration, in addition to becoming wheelchair dependent and bed-ridden at an earlier stage than those who developed these symptoms after three years from symptom onset. Their study also showed that when patients with early autonomic dysfunction develop frequent falling, or wheelchair dependence, or severe dysphagia, or require residential care, there is a shorter interval from this point to death.

In terms of frequency, is estimated at 2 per 100,000, it has identified in different regions of the world. Some clusters of certain types of autosomal dominant cerebellar ataxia reach a prevalence of 5 per 100,000.

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.

The hereditary ataxias are categorized by mode of inheritance and causative gene or chromosomal locus. The hereditary ataxias can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner.

- Many types of autosomal dominant cerebellar ataxias for which specific genetic information is available are now known. Synonyms for autosomal-dominant cerebellar ataxias (ADCA) used prior to the current understanding of the molecular genetics were Marie's ataxia, inherited olivopontocerebellar atrophy, cerebello-olivary atrophy, or the more generic term "spinocerebellar degeneration." (Spinocerebellar degeneration is a rare inherited neurological disorder of the central nervous system characterized by the slow degeneration of certain areas of the brain. There are three forms of spinocerebellar degeneration: Types 1, 2, 3. Symptoms begin during adulthood.)

- There are five typical "autosomal-recessive" disorders in which ataxia is a prominent feature: Friedreich ataxia, ataxia-telangiectasia, ataxia with vitamin E deficiency, ataxia with oculomotor apraxia (AOA), spastic ataxia. Disorder subdivisions: Friedreich's ataxia, Spinocerebellar ataxia, Ataxia telangiectasia, Vasomotor ataxia, Vestibulocerebellar, Ataxiadynamia, Ataxiophemia, Olivopontocerebellar atrophy, and Charcot-Marie-Tooth disease.

- There have been reported cases where a polyglutamine expansion may lengthen when passed down, which often can result in an earlier age-of-onset and a more severe disease phenotype for individuals who inherit the disease allele. This falls under the category of genetic anticipation.

The disease is caused by a mutation in the ATXN3 gene, which is located on chromosome 14q. The gene contains lengthy irregular repetitions of the code "CAG", producing a mutated protein called ataxin-3. (Normally, the number of copies is between 13 and 41.) MJD is an autosomal dominant disease, meaning that if either parent gives the defective gene to a child, the child will show symptoms of the disease. Therefore, if one parent suffers from this disease and the other parent does not, there will be a 50% chance of their child inheriting the disease.

The pons (a structure located on the brain stem) is one of the areas affected by MJD. The striatum (a brain area connected to balance and movement) is also affected by this disease, which could explain both of the main motor problems cause by MJD: the tightening and twisting of the limb and the abrupt, irregular movements.

In affected cells, this protein builds up and assembles intranuclear inclusion bodies. These insoluble aggregates are hypothesized to interfere with the normal activity of the nucleus and induce the cell to degenerate and die.

Neurodegeneration is the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases – including amyotrophic lateral sclerosis, Parkinson's, Alzheimer's, and Huntington's – occur as a result of neurodegenerative processes. Such diseases are incurable, resulting in progressive degeneration and/or death of neuron cells. As research progresses, many similarities appear that relate these diseases to one another on a sub-cellular level. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously. There are many parallels between different neurodegenerative disorders including atypical protein assemblies as well as induced cell death. Neurodegeneration can be found in many different levels of neuronal circuitry ranging from molecular to systemic.

Spinocerebellar ataxia (SCA), also known as spinocerebellar atrophy or spinocerebellar degeneration, is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a disease in its own right. An estimated 150,000 people in the United States have a diagnosis of spinocerebellar ataxia at any given time. SCA is hereditary, progressive, degenerative, and often fatal. There is no known effective treatment or cure. SCA can affect anyone of any age. The disease is caused by either a recessive or dominant gene. In many cases people are not aware that they carry a relevant gene until they have children who begin to show signs of having the disorder.

Currently, no research has shown a higher prevalence of most leukodsytrophy types in any one place around the world. There is, however, a higher prevalence of the Canavan disease in the Jewish population for unknown reasons. 1 in 40 individuals of Ashkenazi Jewish descent are carriers of Canavan disease. This estimates to roughly 2.5%. Additionally, due to an autosomal recessive inheritance patterns, there is no significant difference found between affected males and affected females for most types of leukodystrophy including, but not limited to, metachromatic leukodystrophy, Krabbe disease, Canavan disease, and Alexander disease. The one exception to this is any type of leukodystrophy carried on a sex chromosome, such as X-linked adrenoleukodystrophy, which is carried on the X-chromosome. Because of the inheritance pattern of X-linked diseases, males are more often affected by this type of leukodystrophy, although female carriers are often symptomatic, though not as severely so as males. To date, there have been no found cases of a leukodystrophy carried on the Y chromosome.

HDLS falls under the category of brain white matter diseases called leukoencephalopathies that are characterized by some degree of white matter dysfunction. HDLS has white matter lesions with abnormalities in myelin sheath around axons, where the causative influences are being continually explored based upon recent genetic findings. Studies by Sundal and colleagues from Sweden showed that a risk allele in Caucasians may be causative because cases identified have thus far been among large Caucasian families.

Prognosis strongly depends on which subtype of disease it is. Some are deadly in infancy but most are late onset and mostly manageable.

In terms of the genetics of autosomal dominant cerebellar ataxia 11 of 18 known genes are caused by repeated expansions in corresponding proteins, sharing the same mutational mechanism. SCAs can be caused by conventional mutations or large rearrangements in genes that make glutamate and calcium signaling, channel function, tau regulation and mitochondrial activity or RNA alteration.

The mechanism of Type I is not completely known, however Whaley, et al. suggest the polyglutamine product is toxic to the cell at a protein level, this effect may be done by transcriptional dysregulation and disruption of calcium homeostasis which causes apoptosis to occur earlier.

In those with SS, symptoms typically dramatically improve with low-dose administration of levodopa (L-dopa). L-DOPA exists as a biochemically significant metabolite of the amino acid phenylalanine, as well as a biological precursor of the catecholamine dopamine, a neurotransmitter. (Neurotransmitters are naturally produced molecules that may be sequestered following the propagation of an action potential down a nerve towards the axon terminal, which in turn may cross the synaptic junction between neurons, enabling neurons to communicate in a variety of ways.) Low-dose L-dopa usually results in near-complete or total reversal of all associated symptoms for these patients. In addition, the effectiveness of such therapy is typically long term, without the complications that often occur for those with Parkinson's disease who undergo L-dopa treatment. Thus, most experts indicate that this disorder is most appropriately known as dopa-responsive dystonia (SS).

No data are available on mortality associated with SS, but patients surviving beyond the fifth decade with treatment have been reported. However, in severe, early autosomal recessive forms of the disease, patients have been known to pass away during childhood. Girls seem to be somewhat more commonly affected. The disease less commonly begins during puberty or after age 20, and very rarely, cases in older adults have been reported.

Due to commonly being misdiagnosed, it is common for the disease to remain untreated. When left untreated, patients often need achilles tendon surgery by the age of 21. They will also struggle with walking, an ability that will degrade throughout the day. Power napping can provide temporary relief in untreated patients. It also impairs development into adulthood, reduces balance, and reduces calf muscle development. Socially, it can result in depression, lack of social skills, and inability to find employment.

Neuroferritinopathy or adult-onset basal ganglia disease is a genetic neurodegenerative disorder characterized by the accumulation of iron in the basal ganglia, cerebellum, and motor cortex of the human brain. Symptoms, which are extrapyramidal in nature, progress slowly and generally do not become apparent until adulthood. These symptoms include chorea, dystonia, and cognitive deficits which worsen with age.

This disorder is autosomal dominant and is caused by mutations in the gene encoding the light chain subunit of the ferritin protein. Wild type ferritin functions as a buffer for iron, sequestering it and controlling its release. Thus, mutations in the light chain of ferritin result in the accumulation of iron in the brain which can be imaged using MRI. Currently, neuroferritinopathy is the only neurodegenerative disease with an iron accumulation in the brain classified as an autosomal dominant syndrome.

Treatment of neuroferritinopathy is focused on managing symptoms associated with chorea and dystonia using standard medications for each. The disorder is progressive and symptoms become worse with age. Fewer than 100 cases of neuroferritinopathy have been reported since its identification in 2001. Its incidence has been largely localized to Northeast England suggesting a founder effect. Due to its genetic nature, current research is focused on therapeutic management of the symptoms caused by the disorder.

All brain iron disorders were previously labeled Hallervorden-Spatz syndrome, after the scientists who first discovered individuals with abnormal iron levels in 1922. Brain iron disorders are now divided into three categories: genetic neurodegeneration with brain iron accumulation, genetic systemic iron accumulation with neurologic features, and acquired diseases associated with iron excess or iron deficiency. Neuroferritinopathy is classified under the first category, genetic neurodegeneration with brain iron accumulation. Neuroferritinopathy is classified as a late-onset basal ganglia disease and is a dominantly inherited neurodegenerative disease. Four different alleles are responsible for neuroferritinopathy. Three arise from nucleotide insertions in the ferritin light chain (FTL) polypeptide gene while the fourth arises from a missense mutation in the FTL gene.

Genetic disorders may also be complex, multifactorial, or polygenic, meaning they are likely associated with the effects of multiple genes in combination with lifestyles and environmental factors. Multifactorial disorders include heart disease and diabetes. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person’s risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat, because the specific factors that cause most of these disorders have not yet been identified. Studies which aim to identify the cause of complex disorders can use several methodological approaches to determine genotype-phenotype associations. One method, the genotype-first approach, starts by identifying genetic variants within patients and then determining the associated clinical manifestations. This is opposed to the more traditional phenotype-first approach, and may identify causal factors that have previously been obscured by clinical heterogeneity, penetrance, and expressivity.

On a pedigree, polygenic diseases do tend to "run in families", but the inheritance does not fit simple patterns as with Mendelian diseases. But this does not mean that the genes cannot eventually be located and studied. There is also a strong environmental component to many of them (e.g., blood pressure).

- asthma

- autoimmune diseases such as multiple sclerosis

- cancers

- ciliopathies

- cleft palate

- diabetes

- heart disease

- hypertension

- inflammatory bowel disease

- intellectual disability

- mood disorder

- obesity

- refractive error

- infertility

Specific types of leukodystrophies include the following with their respective ICD-10 codes when available:

- (E71.3) Adrenomyeloneuropathy

- (E75.2) Alexander disease

- (E75.5) Cerebrotendineous xanthomatosis

- Hereditary CNS demyelinating disease

- (E75.2) Krabbe disease

- (E75.2) Metachromatic leukodystrophy

- (E75.2) Pelizaeus–Merzbacher disease

- (E75.2) Canavan disease

- (G93.49) Leukoencephalopathy with vanishing white matter

- (E71.3) Adrenoleukodystrophy

- (G60.1) Refsum disease

Differentiating some kinds of atypical Parkinson: Northwest Parkinson Foundation

Before Parkinson's disease is diagnosed, the differential diagnoses include:

- AIDS can sometimes lead to the symptoms of secondary parkinsonism, due to commonly causing dopaminergic dysfunction. Indeed, parkinsonism can be a presenting feature of HIV infection.

- Corticobasal degeneration

- Creutzfeldt–Jakob disease

- Dementia pugilistica or "boxer's dementia" is a condition that occurs in athletes due to chronic brain trauma.

- Diffuse Lewy body disease

- Drug-induced parkinsonism ("pseudoparkinsonism") due to drugs such as antipsychotics, metoclopramide, sertraline, fluoxetine or the toxin MPTP

- Encephalitis lethargica

- Essential tremor, an illness which has some diagnostic overlap with Parkinson's disease

- Orthostatic tremor

- MDMA addiction and frequent use has been linked to Parkonsonism. Several cases have been reported where individuals are diagnosed with the syndrome after taking MDMA.

- Multiple system atrophy

- Pantothenate kinase-associated neurodegeneration, also known as neurodegeneration with brain iron accumulation or Hallervorden-Spatz syndrome

- Parkinson plus syndrome

- Progressive supranuclear palsy

- Toxicity due to substances such as carbon monoxide, carbon disulfide, manganese, paraquat, mercury, hexane, rotenone, Annonaceae, and toluene (inhalant abuse: "huffing")

- Vascular parkinsonism, associated with underlying cerebrovascular disease

- Wilson's disease is a genetic disorder in which an abnormal accumulation of copper occurs. The excess copper can lead to the formation of a copper-dopamine complex, which leads to the oxidation of dopamine to aminochrome. The most common manifestations include bradykinesia, cogwheel rigidity and a lack of balance.

- Paraneoplastic syndrome: neurological symptoms caused by antibodies associated with cancers

- Genetic

- Rapid onset dystonia parkinsonism

- Parkin mutation

- X-linked dystonia parkinsonism

- Autosomal recessive juvenile parkinsonism

The Roussy–Lévy syndrome is not a fatal disease and life expectancy is normal. However, due to progressive muscle wasting patients may need supportive orthopaedic equipment or wheelchair assistance.

Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia, rigidity, and postural instability. Parkinsonism is found in Parkinson's disease (after which it is named), however a wide range of other causes may lead to this set of symptoms, including some toxins, a few metabolic diseases, and a handful of neurological conditions other than Parkinson's disease.

About 7% of people with parkinsonism have developed their symptoms following treatment with particular medications. Side effect of medications, mainly neuroleptic antipsychotics especially the phenothiazines (such as perphenazine and chlorpromazine), thioxanthenes (such as flupenthixol and zuclopenthixol) and butyrophenones (such as haloperidol), piperazines (such as ziprasidone), and rarely, antidepressants. The incidence of drug-induced parkinsonism increases with age. Drug-induced parkinsonism tends to remain at its presenting level, not progress like Parkinson's disease.

Batten disease is a rare and fatal recessive neurodegenerative disorder that begins at birth.