Saccharopinuria (an excess of saccharopine in the urine), also called saccharopinemia, saccharopine dehydrogenase deficiency or alpha-aminoadipic semialdehyde synthase deficiency, is a variant form of hyperlysinemia. It is caused by a partial deficiency of the enzyme saccharopine dehydrogenase, which plays a secondary role in the lysine metabolic pathway. Inheritance is thought to be autosomal recessive, but this cannot be established as individuals affected by saccharopinuria typically have only a 40% reduction in functional enzyme.

Tyrosinemia type III is a rare disorder caused by a deficiency of the enzyme 4-hydroxyphenylpyruvate dioxygenase (), encoded by the gene "HPD". This enzyme is abundant in the liver, and smaller amounts are found in the kidneys. It is one of a series of enzymes needed to break down tyrosine. Specifically, 4-hydroxyphenylpyruvate dioxygenase converts a tyrosine byproduct called 4-hydroxyphenylpyruvate to homogentisic acid. Characteristic features of type III tyrosinemia include mild mental retardation, seizures, and periodic loss of balance and coordination (intermittent ataxia). Type III tyrosinemia is very rare; only a few cases have been reported.

Paramyotonia congenita is considered an extremely rare disorder, though little epidemiological work has been done. Prevalence is generally higher in European-derived populations and lower among Asians. Epidemiological estimates have been provided for the German population. There, it was estimated that the prevalence of PC is between 1:350,000 (0.00028%) and 1:180,000 (0.00056%). However, the German population of patients with PC is not uniformly distributed across the country. Many individuals with PC herald from the Ravensberg area in North-West Germany, where a founder effect seems to be responsible for most cases. The prevalence here is estimated at 1:6000 or 0.017%.

Hyperlysinemia is an autosomal recessive metabolic disorder characterized by an abnormal increase of lysine in the blood, but appears to be benign. It is caused by mutations in "AASS", which encodes α-aminoadipic semialdehyde synthase.

Hyperlysinemia is associated with ectopia lentis (a displacement or malposition of the eye's crystalline lens) in humans.

A large British study from 2008 found a median estimated life expectancy of 11.6 years.

2,4 Dienoyl-CoA reductase deficiency is an inborn error of metabolism resulting in defective fatty acid oxidation caused by a deficiency of the enzyme 2,4 Dienoyl-CoA reductase. Lysine degradation is also affected in this disorder leading to hyperlysinemia. The disorder is inherited in an autosomal recessive manner, meaning an individual must inherit mutations in "NADK2," located at 5p13.2 from both of their parents. NADK2 encodes the mitochondrial NAD kinase. A defect in this enzyme leads to deficient mitochondrial nicotinamide adenine dinucleotide phosphate levels. 2,4 Dienoyl-CoA reductase, but also lysine degradation are performed by NADP-dependent oxidoreductases explaining how NADK2 deficiency can lead to multiple enzyme defects.

2,4-Dienoyl-CoA reductase deficiency was initially described in 1990 based on a single case of a black female who presented with persistent hypotonia. Laboratory investigations revealed elevated lysine, low levels of carnitine and an abnormal acylcarnitine profile in urine and blood. The abnormal acylcarnitine species was eventually identified as 2-trans,4-cis-decadienoylcarnitine, an intermediate of linoleic acid metabolism. The index case died of respiratory failure at four months of age. Postmortem enzyme analysis on liver and muscle samples revealed decreased 2,4-dienoyl-CoA reductase activity when compared to normal controls. A second case with failure to thrive, developmental delay, lactic acidosis and severe encephalopathy was reported in 2014.

2,4-Dienoyl-CoA reductase deficiency was included as a secondary condition in the American College of Medical Genetics Recommended Uniform Panel for newborn screening. Its status as a secondary condition means there was not enough evidence of benefit to include it as a primary target, but it may be detected during the screening process or as part of a differential diagnosis when detecting conditions included as primary target. Despite its inclusion in newborn screening programs in several states for a number of years, no cases have been identified via neonatal screening.

Some horse organizations have instituted rules to attempt to eliminate this widespread disease. The American Quarter Horse Association (AQHA) mandates testing for foals descended from Impressive if both of the foal's parents were not homozygous negative (N/N) for the gene, and, since 2007, has not registered foals homozygous (H/H) for the gene. Since 2007, the Appaloosa Horse Club (ApHC) has required foals descended from Impressive to be tested, so that the results may be recorded on its certificate. The American Paint Horse Association (APHA) mandated that, after 2017, stallions must be tested for HYPP so that mare owners may make an informed decision before choosing a stallion for breeding to their mare.

Paramyotonia congenita (as well as hyperkalemic periodic paralysis and the potassium-aggravated myotonias) is caused by mutations in a sodium channel, SCN4A. The phenotype of patients with these mutations is indicated in Table 1. These mutations affect fast inactivation of the encoded sodium channel. There are also indications that some mutations lead to altered activation and deactivation. The result of these alterations in channel kinetics is that there is prolonged inward (depolarizing) current following muscle excitation. There is also the introduction of a “window current” due to changes in the voltage sensitivity of the channel’s kinetics. These lead to a general increase in cellular excitability, as shown in figure 1.

There has been one study of a large number of patients with paramyotonia congenita. Of 26 kindreds, it found that 17 (71%) had a mutation in SCN4A while 6 (29%) had no known mutation. There is no large difference between these two groups except that patients with no known mutation have attacks precipitated less by cold but more by hunger, are much more likely to have normal muscle biopsies, and show less decreased compound muscle action potentials when compared to patients with known mutations.

Hyperlysinemia is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

In 1994, researchers at the University of Pittsburgh, with a grant from horse organizations, isolated the genetic mutation responsible for the problem and developed a blood test for it. Using this test, horses may be identified as:

- H/H, meaning they have the mutation and it is homozygous. These horses always pass on the disease.

- N/H, meaning they have the mutation and it is heterozygous. These horses are affected to a lesser degree and pass on the disease 50% of the time.

- N/N, meaning they do not have the mutation and cannot pass it on, even if they are descendants of Impressive.

In the case of the horse Impressive, the muscles were always contracting which was equivalent to a constant work-out. Thus the development of an "impressive" musculature.

Overall, the prognosis for patients with NOMID is not good, though many (80%) live into adulthood, and a few appear to do relatively well. They are at risk for leukemia, infections, and some develop deposits of protein aggregated called amyloid, which can lead to kidney failure and other problems. The neurologic problems are most troubling. The finding that other diseases are related and a better understanding of where the disease comes from may lead to more effective treatments.

Hurler syndrome has an overall frequency of one per 100,000. The mucopolysaccharidoses as a whole have a frequency of one in every 25,000 births.

The prognosis for periodic paralysis varies. Overactivity, a diet that is not low in sodium and carbohydrates, or simply an unfortunate gene mutation can lead to a type of chronic, low level weakness called an "abortive attack," or to permanent muscle damage. Abortive attacks often respond to extra potassium, cutting carbohydrates, getting plenty of rest, increasing doses of medication and gentle daily exercise such as short walks. Permanent muscle weakness is just what it sounds like: Permanent, irreparable damage to the muscles and associated weakness. Vacuoles and tubular aggregates form in and destroy healthy muscle tissue. This type of damage can typically be observed via a muscle biopsy. Not even anabolic steroids can repair this type of muscular damage.

Life span is expected to be normal, but attacks can drop potassium to levels low enough to cause life-threatening breathing problems or heart arrhythmia. Patients often report muscle pain and cognitive problems during attacks. Migraines occur in up to 50% of all hypokalemic periodic paralysis patients and may include less common symptoms like phantom smells, sensitivity to light and sound or loss of words. Medical literatures states that muscle strength is normal between attacks, but patients often report that their baseline strength is in fact lower than that of healthy individuals.

Because there are dozens of possible gene mutations, some drugs and treatments that work fine for one patient will not work for another. For example, most patients do well on acetazolamide, but some don't. Some patients will do well with extra magnesium (the body's natural ion channel blocker) or fish oil, while these same nutrients will make other patients worse. Patients and caregivers should take extreme caution with all new drugs and treatment plans.

This is a rare condition with an incidence estimated to be less than 1 in a million live births. About 100 cases have been reported worldwide. The bulk of cases are sporadic but familial forms with autosomal dominant transmission have also been described.

Urbach–Wiethe disease is very rare; there are fewer than 300 reported cases in medical literature. Although Urbach–Wiethe disease can be found worldwide, almost a quarter of reported diagnoses are in South Africa. Many of these are in patients of Dutch, German, and Khoisan ancestry. This high frequency is thought to be due to the founder effect. Due to its recessive genetic cause and the ability to be a carrier of the disease without symptoms, Urbach–Wiethe disease often runs in families. In some regions of South Africa, up to one in 12 individuals may be carriers of the disease. Most of the case studies involving Urbach–Wiethe disease patients involve only one to three cases and these cases are often in the same family. Due to its low incidence, it is difficult to find a large enough number of cases to adequately study the disease.

While the disability can range from minor, occasional weakness to permanent muscle damage, inability to hold a normal job and use of a powerchair, most people function fairly well with drugs and lifestyle changes.

It is not known how mevalonate kinase mutations cause the febrile episodes, although it is presumed that other products of the cholesterol biosynthesis pathyway, the prenylation chains (geranylgeraniol and farnesol) might play a role.

TPP occurs predominantly in males of Chinese, Japanese, Vietnamese, Filipino, and Korean descent, as well as Thais, with much lower rates in people of other ethnicities. In Chinese and Japanese people with hyperthyroidism, 1.8–1.9% experience TPP. This is in contrast to North America, where studies report a rate of 0.1–0.2%. Native Americans, who share a genetic background with East Asians, are at an increased risk.

The typical age of onset is 20–40. It is unknown why males are predominantly affected, with rates in males being 17- to 70-fold those in females, despite thyroid overactivity being much more common in women.

Periodic paralysis is an autosomal dominant myopathy with considerable variation in penetrance, leading to a spectrum of familial phenotypes (only one parent needs to carry the gene mutation to affect the children, but not all family members who share the gene are affected to the same degree). Specific diseases include:

- Hypokalemic periodic paralysis (), where potassium leaks into the muscle cells from the bloodstream.

- Hyperkalemic periodic paralysis (), where potassium leaks out of the cells into the bloodstream.

- Paramyotonia congenita (), a form which often accompanies hyperkalemic periodic paralysis, but may present alone. The primary symptom of paramyotonia congenita is muscle contracture which develops during exercise or activity. Paramyotonia congenita attacks may also be triggered by a low level of potassium in the bloodstream. This means people with both hyperkalemic periodic paralysis and paramyotonia congenita can have attacks with fluctuations of potassium up or down.

- Andersen-Tawil syndrome (), a form of periodic paralysis that includes significant heart rhythm problems, fainting and risk of sudden death. Potassium levels may be low, high, or normal during attacks of ATS. Patients with ATS may also have skeletal abnormalities like scoliosis (curvature of the spine), webbing between the second and third toes or fingers (syndactyly), crooked fingers (clinodactyly), a small jaw (micrognathia) and low-set ears. Patients need to have another form of periodic paralysis to have the Andersen-Tawil. If a patient has hypo or hyper periodic paralysis they have a 50% chance of getting Andersen-Tawil. They just have to have the gene that causes it. This is a rare occurrence of having this. Only around 100 people in the world are recorded to have it.

Genetic mutations in the L-type calcium channel α1-subunit (Ca1.1) have been described in Southern Chinese with TPP. The mutations are located in a different part of the gene from those described in the related condition familial periodic paralysis. In TPP, the mutations described are single-nucleotide polymorphisms located in the hormone response element responsive to thyroid hormone, implying that transcription of the gene and production of ion channels may be altered by increased thyroid hormone levels. Furthermore, mutations have been reported in the genes coding for potassium voltage-gated channel, Shaw-related subfamily, member 4 (K3.4) and sodium channel protein type 4 subunit alpha (Na1.4).

Of people with TPP, 33% from various populations were demonstrated to have mutations in "KCNJ18", the gene coding for K2.6, an inward-rectifier potassium ion channel. This gene, too, harbors a thyroid response element.

Certain forms of human leukocyte antigen (HLA)—especially B46, DR9, DQB1*0303, A2, Bw22, AW19, B17, and DRW8—are more common in TPP. Linkage to particular forms of HLA, which plays a central role in the immune response, might imply an immune system cause, but it is uncertain whether this directly causes TPP or whether it increases the susceptibility to Graves' disease, a known autoimmune disease.

Hypokalemic periodic paralysis (hypoKPP) is a rare, autosomal dominant channelopathy characterized by muscle weakness or paralysis when there is a fall in potassium levels in the blood. In individuals with this mutation, attacks often begin in adolescence and most commonly occur on awakening or after sleep or rest following strenuous exercise (attacks during exercise are rare), high carbohydrate meals, meals with high sodium content, sudden changes in temperature, and even excitement, noise, flashing lights and cold temperatures. Weakness may be mild and limited to certain muscle groups, or more severe full-body paralysis. During an attack reflexes may be decreased or absent. Attacks may last for a few hours or persist for several days. Recovery is usually sudden when it occurs, due to release of potassium from swollen muscles as they recover. Some patients may fall into an abortive attack or develop chronic muscle weakness later in life.

Some people only develop symptoms of periodic paralysis due to hyperthyroidism (overactive thyroid). This entity is distinguished with thyroid function tests, and the diagnosis is instead called thyrotoxic periodic paralysis.

Channelopathies are diseases caused by disturbed function of ion channel subunits or the proteins that regulate them. These diseases may be either congenital (often resulting from a mutation or mutations in the encoding genes) or acquired (often resulting from autoimmune attack on an ion channel).

There are a large number of distinct dysfunctions known to be caused by ion channel mutations. The genes for the construction of ion channels are highly conserved amongst mammals and one condition, hyperkalemic periodic paralysis, was first identified in the descendants of Impressive, a registered Quarter Horse (see AQHA website).

The channelopathies of human skeletal muscle include hyper- and hypokalemic (high and low potassium blood concentrations) periodic paralysis, myotonia congenita and paramyotonia congenita.

Channelopathies affecting synaptic function are a type of synaptopathy.

Respiratory complications are often cause of death in early infancy.

Virtually all people with the syndrome have mutations in the gene for mevalonate kinase, which is part of the HMG-CoA reductase pathway, an important cellular metabolic pathway. Indeed, similar fever attacks (but normal IgD) have been described in patients with mevalonic aciduria – an inborn error of metabolism now seen as a severe form of HIDS.

Urbach–Wiethe disease is typically not a life-threatening condition. The life expectancy of these patients is normal as long as the potential side effects of thickening mucosa, such as respiratory obstruction, are properly addressed. Although this may require a tracheostomy or carbon dioxide laser surgery, such steps can help ensure that individuals with Urbach–Wiethe disease are able to live a full life. Oral dimethyl sulfoxide (DMSO) has been shown to reduce skin lesions, helping to minimize discomfort for these individuals.