As of June 2014 (the latest update on HFM in GeneReviews) a total of 32 families had been reported with a clinical diagnosis of HFM of which there was genotypic confirmation in 24 families. Since then, another two confirmed cases have been reported and an additional case was reported based on a clinical diagnosis alone. Most cases emerge from consanguineous parents with homozygous mutations. There are three instances of HFM from non-consanguineous parents in which there were heterozygous mutations. HFM cases are worldwide with mostly private mutations. However, a number of families of Puerto Rican ancestry have been reported with a common pathogenic variant at a splice receptor site resulting in the deletion of exon 3 and the absence of transport function. A subsequent population-based study of newborn infants in Puerto Rico identified the presence of the same variant on the island. Most of the pathogenic variants result in a complete loss of the PCFT protein or point mutations that result in the complete loss of function. However, residual function can be detected with some of the point mutants.

Population-based studies of KLS have not been performed. Its prevalence is about 1 case per million people. In France, KLS has a prevalence of 1.5 per million people. It occurs most frequently among Jews in the US and Israel. First-degree relatives of people who have suffered from the syndrome are much more likely than the general population to suffer from it, although only in about one percent of cases do family members contract it. About 70 to 90 percent of patients are male. Patients with the syndrome are more likely than the general population to have genetic disorders, and about a third of people with the syndrome encountered some form of birth difficulty. In a study of 186 older patients, about ten percent had preexisting psychiatric issues. One study found that about ten percent of patients had a neurological condition before KLS developed. The condition does not appear to occur most frequently in one season.

The frequency of KLS episodes can vary from attacks one week in length occurring twice a year to dozens of episodes that follow each other in close succession. The median duration of KLS episodes is about ten days, but some last several weeks or months. A study of 108 patients found an average of 19 episodes over the duration of the disease. Another study found a median of 3.5 months between episodes. Outside of episodes, there is no disturbance in patients' sleep patterns and they are generally asymptomatic. Patients do not experience the same symptoms in each episode.

About 80 percent of patients are adolescents when they first experience KLS. On some occasions though, its first occurrence comes in childhood or adulthood. In most adolescent-onset patients, symptoms cease by the time they are 30 years old. A French study of 108 patients found a median duration of 13 years, but a review of 186 cases found a median duration of 8 years. Unusually young or old patients and those who experience hypersexuality tend to have a more severe course. Patients who initially have frequent attacks generally see the disease cease earlier than others. The condition spontaneously resolves, and the patient is considered to be cured if there have been no symptoms for six years.

Glyceraldehyde 3-phosphate dehydrogenase (abbreviated as GAPDH or less commonly as G3PDH) () is an enzyme of ~37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. In addition to this long established metabolic function, GAPDH has recently been implicated in several non-metabolic processes, including transcription activation, initiation of apoptosis, ER to Golgi vesicle shuttling, and fast axonal, or axoplasmic transport. In sperm, a testis-specific isoenzyme GAPDHS is expressed.

Cross-tolerance is a phenomenon that occurs when tolerance to the effects of a certain drug produces tolerance to another drug. It often happens between two drugs with similar functions or effects – for example, acting on the same cell receptor or affecting the transmission of certain neurotransmitters. Cross-tolerance has been observed with pharmaceutical drugs such as anti-anxiety agents and illicit substances, and sometimes the two of them together. Often, a person who uses one drug can be tolerant to a drug that has a completely different function. This phenomenon allows one to become tolerant to a drug that they have never even used before.

Hartnup disease (also known as "pellagra-like dermatosis" and "Hartnup disorder") is an autosomal recessive metabolic disorder affecting the absorption of nonpolar amino acids (particularly tryptophan that can be, in turn, converted into serotonin, melatonin, and niacin). Niacin is a precursor to nicotinamide, a necessary component of NAD+.

The causative gene, "SLC6A19", is located on chromosome 5.

Maternal consequences include the following:

- Itching, which can become intense and debilitating

- Premature labor

- Deranged clotting, which requires Vitamin K

Fetal consequences include:

- Fetal distress

- Meconium ingestion

- Meconium aspiration syndrome

- Stillbirth

Delivery has been recommended in the 38th week when lung maturity has been established.

Central nervous system fatigue, or central fatigue, is a form of fatigue that is associated with changes in the synaptic concentration of neurotransmitters within the central nervous system (CNS; including the brain and spinal cord) which affects exercise performance and muscle function and cannot be explained by peripheral factors that affect muscle function. In healthy individuals, central fatigue can occur from prolonged exercise and is associated with neurochemical changes in the brain, primarily involving serotonin (5-HT), noradrenaline, and dopamine. Central fatigue plays an important role in endurance sports and also highlights the importance of proper nutrition in endurance athletes.

Chronic fatigue syndrome is a name for a group of diseases that are dominated by persistent fatigue. The fatigue is not due to exercise and is not relieved by rest.

Through numerous studies, it has been shown that people with chronic fatigue syndrome have an integral central fatigue component. In one study, the subjects' skeletal muscles were checked to ensure they had no defects that prevented their total use. It was found that the muscles functioned normally on a local level, but they failed to function to their full extent as a whole. The subjects were unable to consistently activate their muscles during sustained use, despite having normal muscle tissue. In another study, the subjects experienced higher perceived effort in relation to heart rate as compared to the control during a graded exercise test. The chronic fatigue subjects would stop before any sort of limit on the body was reached. Both studies proved that peripheral muscle fatigue was not causing the subjects with chronic fatigue syndrome to cease exercising. It is possible that the higher perception of effort required to use the muscles results in great difficulty in accomplishing consistent exercise. The main cause of fatigue in chronic fatigue syndrome most likely lies in the central nervous system. A defect in one of its components could cause a greater requirement of input to result in sustained force. It has been shown that with very high motivation, subjects with chronic fatigue can exert force effectively. Further investigation into central nervous system fatigue may result in medical applications.

Treatment with progesterone in the third trimester of pregnancy has been shown to be associated with the development of ICP, and levels of metabolites of progesterone, particularly sulfated progesterone, are higher in patients with ICP than unaffected women, suggesting that progesterone also has a role in ICP.

Hartnup disease is inherited as an autosomal recessive trait. Heterozygotes are normal. Consanguinity is common. The failure of amino-acid transport was reported in 1960 from the increased presence of indoles (bacterial metabolites of tryptophan) and tryptophan in the urine of patients as part of a generalized aminoaciduria of the disease. The excessive loss of tryptophan from malabsorption was the cause of the pellagra like symptoms. From studies on ingestion of tryptophan it seemed that there was a generalized problem with amino-acid transport. In 2004, a causative gene, "SLC6A19", was located on band 5p15.33. "SLC6A19" is a sodium-dependent and chloride-independent neutral amino acid transporter, expressed predominately in the kidneys and intestine.

Sometimes cross-tolerance occurs between two drugs that do not share mechanisms of action or classification. For example, amphetamine and amphetamine-like stimulants have been shown to exhibit cross-tolerance with caffeine, and it is likely the mechanism of cross-tolerance involves the dopamine receptor D. Amphetamines also have cross-tolerance with pseudoephedrine, as pseudoephedrine can block dopamine uptake in the same manner that amphetamines do, but less potently.

Alcohol is another substance that often cross-tolerates with other drugs. Findings of cross-tolerance with nicotine in animal models suggest that it is also possible in humans, and may explain why the two drugs are often used together. Numerous studies have also suggested the possibility of cross-tolerance between alcohol and cannabis.

Hereditary folate malabsorption (HFM - OMIM #229050) is a rare autosomal recessive disorder caused by loss-of-function mutations in the proton-coupled folate transporter (PCFT) gene, resulting in systemic folate deficiency and impaired delivery of folate to the brain.

It is difficult to differentiate the effects of low level metal poisoning from the environment with other kinds of environmental harms, including nonmetal pollution. Generally, increased exposure to heavy metals in the environment increases risk of developing cancer.

Without a diagnosis of metal toxicity and outside of evidence-based medicine, but perhaps because of worry about metal toxicity, some people seek chelation therapy to treat autism, cardiovascular disease, Alzheimer's disease, or any sort of neurodegeneration. Chelation therapy does not improve outcomes for those diseases.

Removing the pig from the stressful situation can prevent the episode.

Sedation and glucocorticoids may be beneficial.

Under anaesthesia, dantrolene sodium is a very effective treatment.

Genetic testing enables animals to be removed from the herd if they are positive for the gene. This means that the disorder is rare in the developed world these days.

Stress at slaughter should be minimised in all cases.

Increased consumption of zinc is another cause of copper deficiency. Zinc is often used for the prevention or treatment of common colds and sinusitis (inflammation of sinuses due to an infection), ulcers, sickle cell disease, celiac disease, memory impairment and acne. Zinc is found in many common vitamin supplements and is also found in denture creams. Recently, several cases of copper deficiency myeloneuropathy were found to be caused by prolonged use of denture creams containing high quantities of zinc.

Metallic zinc is the core of all United States currency coins, including copper coated pennies. People who ingest a large number of coins will have elevated zinc levels, leading to zinc-toxicity-induced copper deficiency and the associated neurological symptoms. This was the case for a 57-year-old woman diagnosed with schizophrenia. The woman consumed over 600 coins, and started to show neurological symptoms such as unsteady gait and mild ataxia.

GAPDH has been implicated in several neurodegenerative diseases and disorders, largely through interactions with other proteins specific to that disease or disorder. These interactions may affect not only energy metabolism but also other GAPDH functions. For example, GAPDH interactions with beta-amyloid precursor protein (betaAPP) could interfere with its function regarding the cytoskeleton or membrane transport, while interactions with huntingtin could interfere with its function regarding apoptosis, nuclear tRNA transport, DNA replication, and DNA repair. In addition, nuclear translocation of GAPDH has been reported in Parkinson's disease (PD), and several anti-apoptotic PD drugs, such as rasagiline, function by preventing the nuclear translocation of GAPDH. It is proposed that hypometabolism may be one contributor to PD, but the exact mechanisms underlying GAPDH involvement in neurodegenerative disease remains to be clarified. The SNP rs3741916 in the 5' UTR of the "GAPDH" gene may be associated with late onset Alzheimer's disease.

Copper toxicity, also called copperiedus, refers to the consequences of an excess of copper in the body. Copperiedus can occur from eating acid foods cooked in uncoated copper cookware, or from exposure to excess copper in drinking water, as a side-effect of estrogen birth control pills, or other environmental sources. It can also result from the genetic condition Wilson's disease.

Several studies have shown that the risk of suicide is higher in patients who suffer from Bipolar II than those who suffer from Bipolar I, and especially higher than patients who suffer from major depressive disorder.

In results of a summary of several lifetime study experiments, it was found that 24% of Bipolar II patients experienced suicidal ideation or suicide attempts compared to 17% in Bipolar I patients and 12% in major depressive patients. Bipolar disorders, in general, are the third leading cause of death in 15- to 24-year-olds. Bipolar II patients were also found to employ more lethal means and have more complete suicides overall.

Bipolar II patients have several risk factors that increase their risk of suicide. The illness is very recurrent and results in severe disabilities, interpersonal relationship problems, barriers to academic, financial, and vocational goals, and a loss of social standing in their community, all of which increase the likelihood of suicide. Mixed symptoms and rapid-cycling, both very common in Bipolar II, are also associated with an increased risk of suicide. The tendency for Bipolar II to be misdiagnosed and treated ineffectively, or not at all in some cases, leads to an increased risk.

As a result of the high suicide risk for this group, reducing the risk and preventing attempts remains a main part of the treatment; a combination of self-monitoring, close supervision by a therapist, and faithful adherence to their medication regimen will help to reduce the risk and prevent the likelihood of a completed suicide.

Usually there are brief, arrhythmic interruptions of sustained voluntary muscle contraction causing brief lapses of posture, with a frequency of 3–5 Hz. It is bilateral, but may be asymmetric. Unilateral asterixis may occur with structural brain disease.

- It can be a sign of hepatic encephalopathy, damage to brain cells presumably due to the inability of the liver to metabolize ammonia to urea. The cause is thought to be predominantly related to abnormal ammonia metabolism.

- Asterixis is seen most often in drowsy or stuporous patients with metabolic encephalopathies, especially in decompensated cirrhosis or acute liver failure.

- It is also seen in some patients with kidney failure and azotemia, and in carbon dioxide toxicity.

- It can also be a feature of Wilson's disease.

- Asterixis is also seen in respiratory failure.

- Some drugs are known to cause asterixis, particularly phenytoin (when it is known as phenytoin flap). Other drugs implicated include benzodiazepines, barbiturates, valproate, gabapentin, lithium, ceftazidime, and metoclopramide.

Bariatric surgery is a common cause of copper deficiency. Bariatric surgery, such as gastric bypass surgery, is often used for weight control of the morbidly obese. The disruption of the intestines and stomach from the surgery can cause absorption difficulties not only as regards copper, but also for iron and vitamin B12 and many other nutrients. The symptoms of copper deficiency myelopathy may take a long time to develop, sometimes decades before the myelopathy symptoms manifest.

Porcine stress syndrome, also known as malignant hyperthermia or PSS, is a condition in pigs. It is characterised by hyperthermia triggered by stress, anaesthesia with halothane or intense exercise. PSS may appear as sudden death in pigs, often after transport. It is an inherited, autosomal recessive disorder due to a defective ryanodine receptor leading to huge calcium influx, muscle contracture and increase in metabolism.

PSS can manifest itself in the abattoir as the production of Pale, Soft and Exudative meat due to a rapid fall in muscle pH and degradation of muscle proteins and structure. This meat is usually rejected after inspection.

This disorder is most common in Landrace, Piétrain and crossbreeds of these breeds of pig. The genes may have been favoured in the past due to a larger muscle bulk in these breeds. However this is not standard protocol in developed countries these days.

Some patients who are diagnosed with treatment-resistant depression may have an underlying undiagnosed health condition that is causing or contributing to their depression. Endocrine disorders like hypothyroidism, Cushing's disease, and Addison's disease are among the most commonly identified as contributing to depression. Others include diabetes, coronary artery disease, cancer, HIV, and Parkinson's disease.

Another factor is that medications used to treat comorbid medical disorders may lessen the effectiveness of antidepressants or cause depression symptoms.

The more common and serious version of Canavan disease typically result in death or development of life-threatening conditions by the age of ten, though life expectancy is variable, and is highly dependent on specific circumstances. On the other hand, the milder variants of the disorder seem not to have any effect on lifespan.

Chylomicron retention disease is a disorder of fat absorption. It is associated with SAR1B. Mutations in SAR1B prevent the release of chylomicrons in the circulation which leads to nutritional and developmental problems. It is a rare autosomal recessive disorder with around 40 cases reported worldwide. Since the disease allele is recessive, parents usually do not show symptoms.

Without functional chylomicrons certain fat-soluble vitamins such as vitamin D and vitamin E cannot be absorbed. Chylomicrons have a crucial role in fat absorption and transport, thus deficiency in chylomicron functioning reduces available levels of dietary fats and fat-soluble vitamins.