Current research suggests that nearly 8% of the population has at least partial DPD deficiency. A diagnostics determination test for DPD deficiency is available and it is expected that with a potential 500,000 people in North America using 5-FU this form of testing will increase. The whole genetic events affecting the DPYD gene and possibly impacting on its function are far from being elucidated, and epigenetic regulations could probably play a major role in DPD deficiency. It seems that the actual incidence of DPD deficiency remains to be understood because it could depend on the very technique used to detect it. Screening for genetic polymorphisms affecting the "DPYD" gene usually identify less than 5% of patients bearing critical mutations, whereas functional studies suggest that up to 20% of patients could actually show various levels of DPD deficiency.

Women could be more at risk than men. It is more common among African-Americans than it is among Caucasians.

Studies indicate that persons with symptomatic haemochromatosis have somewhat reduced life expectancy compared to the general population. This is mainly due to excess mortality from cirrhosis and liver cancer. Patients who were treated with phlebotomy lived longer than those who weren't. Patients without liver disease or diabetes had similar survival rate to the general population.

Juvenile hemochromatosis (or hemochromatosis type 2) is, as its name indicates, a form of hemochromatosis which emerges during youth.

There are two forms:

- "HFE2A" is associated with hemojuvelin

- "HFE2B" is associated with hepcidin antimicrobial peptide

Some sources only specifically include hemojuvelin as a cause of juvenile hemochromatosis.

Haemochromatosis is one of the most common heritable genetic conditions in people of northern European extraction with a prevalence of 1 in 200. The disease has a variable penetration and about 1 in 10 people of this demographic carry a mutation in one of the genes regulating iron metabolism, the most common allele being the C282Y allele in the "HFE" gene. The prevalence of mutations in iron metabolism genes varies in different populations. A study of 3,011 unrelated white Australians found that 14% were heterozygous carriers of an HFE mutation, 0.5% were homozygous for an "HFE" mutation, and only 0.25% of the study population had clinically relevant iron overload. Most patients who are homozygous for HFE mutations will not manifest clinically relevant haemochromatosis (see Genetics above). Other populations have a lower prevalence of both the genetic mutation and the clinical disease.

Genetic studies suggest the original haemochromatosis mutation arose in a single person, possibly of Celtic ethnicity, who lived 60–70 generations ago. At that time when dietary iron may have been scarcer than today, the presence of the mutant allele may have provided an evolutionary or natural selection reproductive advantage by maintaining higher iron levels in the blood.

Affected individuals over age 40 or who have high serum ferritin levels are at risk for developing cirrhosis. Iron overload increases the risk of hepatocellular carcinoma. This risk is greater in those with cirrhosis but is still present in those without cirrhosis. Significant problems occur in around one in ten.

It is most common in certain European populations (such as the Irish and Norwegians) and occurs in 0.6% of the population. Men with the disease are 24 times more likely to experience symptoms than affected women.

Since the essential pathology is due to the inability to absorb vitamin B from the bowels, the solution is therefore injection of IV vitamin B. Timing is essential, as some of the side effects of vitamin B deficiency are reversible (such as RBC indices, peripheral RBC smear findings such as hypersegmented neutrophils, or even high levels of methylmalonyl CoA), but some side effects are irreversible as they are of a neurological source (such as tabes dorsalis, and peripheral neuropathy). High suspicion should be exercised when a neonate, or a pediatric patient presents with anemia, proteinuria, sufficient vitamin B dietary intake, and no signs of pernicious anemia.

Genes involved in iron metabolism disorders include HFE and TFR2.

Hepcidin is the master regulator of iron metabolism and, therefore, most genetic forms of iron overload can be thought of as relative hepcidin deficiency in one way or another. For instance, a severe form of iron overload, juvenile hemochromatosis, is a result of severe hepcidin deficiency. The majority of cases are caused by mutations in the hemojuvelin gene (HJV or RGMc/repulsive guidance molecule c). The exceptions, people who have mutations in the gene for ferroportin, prove the rule: these people have plenty of hepcidin, but their cells lack the proper response to it. So, in people with ferroportin proteins that transport iron out of cells without responding to hepcidin's signals to stop, they have a deficiency in the action of hepcidin, if not in hepcidin itself.

But the exact mechanisms of most of the various forms of adult hemochromatosis, which make up most of the genetic iron overload disorders, remain unsolved. So while researchers have been able to identify genetic mutations causing several adult variants of hemochromatosis, they now must turn their attention to the normal function of these mutated genes.

These genes represent multiple steps along the pathway of iron regulation, from the body's ability to sense iron, to the body's ability to regulate uptake and storage. Working out the functions of each gene in this pathway will be an important tool for finding new methods of treating genetic disorders, as well as for understanding the basic workings of the pathway.

So though many mysteries of iron metabolism remain, the discovery of hepcidin already allows a much better understanding of the nature of iron regulation, and makes researchers optimistic that many more breakthroughs in this field are soon to come.

Pyruvate kinase deficiency happens worldwide, however northern Europe, and Japan have many cases. The prevalence of pyruvate kinase deficiency is around 51 cases per million in the population (via gene frequency).

A small number of genetic variants have been repeatedly associated with DPD deficiency, such as IVS14+1G>A mutation in intron 14 coupled with exon 14 deletion (a.k.a. DPYD*2A), 496A>G in exon 6; 2846A>T in exon 22 and T1679G (a.k.a. DPYD*13) in exon 13. However, testing patients for these allelic variants usually show high specificity (i.e., bearing the mutation means that severe toxicity will occur indeed)but very low sentivity (i.e., not bearing the mutation does not mean that there is no risk for severe toxicities). Alternatively, phenotyping DPD using ex-vivo enzymatic assay or surrogate testing (i.e., monitoring physiological dihydrouracil to uracil ratio in plasma) has been presented as a possible upfront strategy to detect DPD deficiency. 5-FU test dose (i.e., preliminary administration of a small dose of 5-FU with pharmacokinetics evaluation) has been proposed as another possible alternative strategy to secure the use of fluoropyrimidine drugs.

This is a rare disease with prevalence about 1 in 200,000 to 1 in 600,000. Studies showed that mutations in "CUBN" or "AMN" clustered particularly in the Scandinavian countries and the Eastern Mediterranean regions. Founder effect, higher clinical awareness to IGS, and

frequent consanguineous marriages all play a role in the higher prevalence of IGS among these populations

Tricho-hepato-enteric syndrome is estimated to affect 1 in 300,000 to 400,000 live births in Western Europe. This syndrome was first reported in 1982 with a report on 2 siblings, and as of 2008 there were around 25 published cases in medical journals. There seem to be no racial differences in its occurrence. It might be more common, as many genetic diseases, in areas with high levels of consanguinity.

While inherited deficiencies in uroporphyrinogen decarboxylase often lead to the development of PCT, there are a number of risk factors that can both cause and exacerbate the symptoms of this disease. One of the most common risk factors observed is infection with the Hepatitis C virus. One review of a collection of PCT studies noted Hepatitis C infection in 50% of documented cases of PCT. Additional risk factors include alcohol abuse, excess iron (from iron supplements as well as cooking on cast iron skillets), and exposure to chlorinated cyclic hydrocarbons and Agent Orange.

It can be a paraneoplastic phenomenon.

Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells. Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and more commonly, the inheritance is autosomal recessive. Pyruvate kinase deficiency is the second most common cause of enzyme-deficient hemolytic anemia, following G6PD deficiency.

Tricho-hepato-enteric syndrome (THE), also known as syndromic or phenotypic diarrhea, is an extremely rare congenital bowel disorder which manifests itself as intractable diarrhea in infants with intrauterine growth retardation, hair and facial abnormalities. Many also have liver disease and abnormalities of the immune system. The associated malabsorption leads to malnutrition and failure to thrive.

It is thought to be a genetic disorder with an autosomal recessive inheritance pattern, although responsible genes have not been found and the exact cause remains unknown. Prognosis is poor; many patients die before the age of 5 (mainly from infections or cirrhosis), although most patients nowadays survive with intravenous feeding (parenteral nutrition).

Porphyria cutanea tarda has a prevalence estimated at approximately 1 in 10,000. An estimated 80% of porphyria cutanea tarda cases are sporadic. The exact frequency is not clear because many people with the condition never experience symptoms and those that do are often misdiagnosed with anything ranging from idiopathic photodermatitis and seasonal allergies to hives.

The causes of neonatal hemochromatosis are still unknown, but recent research has led to the hypothesis that it is an alloimmune disease. Evidence supporting this hypothesis includes the high rate among siblings (>80%). This evidence along with other research indicates that neonatal hemochromatosis could be classified as a congenital alloimmune hepatitis.

The condition is sometimes confused with juvenile hemochromatosis, which is a hereditary hemochromatosis caused by mutations of a gene called hemojuvelin. While the symptoms and outcomes for these two diseases are similar, the causes appear to be different.

By 1990, 65 patients had been reported in the literature, with no sex or ethnic preference notable. Some individuals present with minimal malformation; rarely patients have died during infancy as a result of severe central nervous system involvement or respiratory complications. Several syndromes are related to the Freeman–Sheldon syndrome spectrum, but more information is required before undertaking such nosological delineation.

There are little data on prognosis. Rarely, some patients have died in infancy from respiratory failure; otherwise, life expectancy is considered to be normal.

By definition, primary immune deficiencies are due to genetic causes. They may result from a single genetic defect, but most are multifactorial. They may be caused by recessive or dominant inheritance. Some are latent, and require a certain environmental trigger to become manifest, like the presence in the environment of a reactive allergen. Other problems become apparent due to aging of bodily and cellular maintenance processes.

These are a few specialized autoimmune disorders resulting from environmental rather than genetic causes, which mimic the genotypic disorders.

Kohlschütter-Tönz syndrome (KTS), also called Amelo-cerebro-hypohidrotic syndrome is a rare inherited syndrome characterized by epilepsy, dementia, intellectual disability, and yellow teeth caused by amelogenesis imperfecta (abnormal formation of tooth enamel). It is a type A ectodermal dysplasia.

It is autosomal recessive and symptoms appear in early childhood. The syndrome was first described in 1974 by Alfried Kohlschütter and colleagues. Only 24 affected individuals are known as of 2012. The disease has not been connected to any other known epileptic syndromes. Some but not all cases are associated with mutations in a gene called ROGDI. Another gene that has been associated with this condition is the SCL13A5 gene Diagnoses of this syndrome have occurred in Switzerland, Sicily, the Northern Israel Druze community as well as some other parts of Western Europe.

Hemosiderosis (AmE) or haemosiderosis (BrE) is a form of iron overload disorder resulting in the accumulation of hemosiderin.

Types include:

- Transfusion hemosiderosis

- Idiopathic pulmonary hemosiderosis

- Transfusional diabetes

Hemosiderin deposition in the lungs is often seen after diffuse alveolar hemorrhage, which occurs in diseases such as Goodpasture's syndrome, granulomatosis with polyangiitis, and idiopathic pulmonary hemosiderosis. Mitral stenosis can also lead to pulmonary hemosiderosis. Hemosiderin collects throughout the body in hemochromatosis. Hemosiderin deposition in the liver is a common feature of hemochromatosis and is the cause of liver failure in the disease. Selective iron deposition in the beta cells of pancreatic islets leads to diabetes due to distribution of transferrin receptor on the beta cells of islets and in the skin leads to hyperpigmentation. Hemosiderin deposition in the brain is seen after bleeds from any source, including chronic subdural hemorrhage, cerebral arteriovenous malformations, cavernous hemangiomata. Hemosiderin collects in the skin and is slowly removed after bruising; hemosiderin may remain in some conditions such as stasis dermatitis. Hemosiderin in the kidneys has been associated with marked hemolysis and a rare blood disorder called paroxysmal nocturnal hemoglobinuria.

Hemosiderin may deposit in diseases associated with iron overload. These diseases are typically diseases in which chronic blood loss requires frequent blood transfusions, such as sickle cell anemia and thalassemia, though beta thalassemia minor has been associated with hemosiderin deposits in the liver in those with non-alcoholic fatty liver disease independent of any transfusions.

Diagnosis occurs based on the two most common features of this syndrome: epilepsy and symmetrical enamel hypoplasia also known as Amelogenesis Imperfecta. Because the tooth discoloration caused by amelogensis imperfecta is often thought to be caused by environmental factors or other diseases, diagnosis of this syndrome is sometimes overlooked. The onset of symptoms can occur when the patient is between one month and four years old, contributing to the misconception that tooth discoloration is due to the environment.