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.

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.

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.

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.

These differ according to the type of chronic liver disease.

- Excessive alcohol use

- Obesity

- Metabolic syndrome including raised blood lipids

- Health care professionals who are exposed to body fluids and infected blood

- Sharing infected needle and syringes

- Having unprotected sex and multiple sex partners

- Working with toxic chemicals without wearing safety clothes

- Certain prescription medications

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.

The list of conditions "associated" with chronic liver disease is extensive and can be categorised in the following way:

Viral causes

- Hepatitis B

- Hepatitis C

Cytomegalovirus (CMV), Epstein Barr virus (EBV), and yellow fever viruses cause acute hepatitis.

Toxic and drugs

- Alcoholic liver disease

- Rarely drug induced liver disease from methotrexate, amiodarone, nitrofurantoin and others

Paracetamol (acetaminophen) causes acute liver damage.

Metabolic

- Non-alcoholic fatty liver disease

- Haemochromatosis

- Wilson’s disease

Autoimmune response causes

- Primary biliary cholangitis (previously known as primary biliary cirrhosis)

- Primary sclerosing cholangitis

Other

- Right heart failure

Hereditary spherocytosis is the most common disorder of the red cell membrane and affects 1 in 2,000 people of Northern European ancestry. According to Harrison's Principles of Internal Medicine, the frequency is at least 1 in 5,000.

Basically classified by causative mechanism, types of congenital hemolytic anemia include:

- Genetic conditions of RBC Membrane

- Hereditary spherocytosis

- Hereditary elliptocytosis

- Genetic conditions of RBC metabolism (enzyme defects). This group is sometimes called "congenital nonspherocytic (hemolytic) anemia", which is a term for a congenital hemolytic anemia without spherocytosis, and usually excluding hemoglobin abnormalities as well, but rather encompassing defects of glycolysis in the erythrocyte.

- Glucose-6-phosphate dehydrogenase deficiency (G6PD or favism)

- Pyruvate kinase deficiency

- Aldolase A deficiency

- Hemoglobinopathies/genetic conditions of hemoglobin

- Sickle cell anemia

- Congenital dyserythropoietic anemia

- Thalassemia

Experimental gene therapy exists to treat hereditary spherocytosis in lab mice; however, this treatment has not yet been tried on humans due to all of the risks involved in human gene therapy.

Those with hereditary elliptocytosis have a good prognosis, only those with very severe disease have a shortened life expectancy.

Congenital hemolytic anemia (or hereditary hemolytic anemia) refers to hemolytic anemia which is primarily due to congenital disorders.

The incidence of hereditary elliptocytosis is hard to determine, as many sufferers of the milder forms of the disorder are asymptomatic and their condition never comes to medical attention. Around 90% of those with this disorder are thought to fall into the asymptomatic population. It is estimated that its incidence is between 3 and 5 per 10,000 in the United States, and that those of African and Mediterranean descent are of higher risk. Because it can confer resistance to malaria, some subtypes of hereditary elliptocytosis are significantly more prevalent in regions where malaria is endemic. For example, in equatorial Africa its incidence is estimated at 60-160 per 10,000, and in Malayan natives its incidence is 1500-2000 per 10,000. Almost all forms of hereditary elliptocytosis are autosomal dominant, and both sexes are therefore at equal risk of having the condition. The most important exception to this rule of autosomal dominance is for a subtype of hereditary elliptocytosis called hereditary pyropoikilocytosis (HPP), which is autosomal recessive.

There are three major forms of hereditary elliptocytosis: common hereditary elliptocytosis, spherocytic elliptocytosis and southeast Asian ovalocytosis.

Common hereditary elliptocytosis is the most common form of elliptocytosis, and the form most extensively researched. Even when looking only at this form of elliptocytosis, there is a high degree of variability in the clinical severity of its subtypes. A clinically significant haemolytic anaemia occurs only in 5-10% of sufferers, with a strong bias towards those with more severe subtypes of the disorder.

Southeast Asian ovalocytosis and spherocytic elliptocytosis are less common subtypes predominantly affecting those of south-east Asian and European ethnic groups, respectively.

The following categorisation of the disorder demonstrates its heterogeneity:

- Common hereditary elliptocytosis (in approximate order from least severe to most severe)

- With asymptomatic carrier status - "individuals have no symptoms of disease and diagnosis is only able to be made on blood film"

- With mild disease - "individuals have no symptoms, with a mild and compensated haemolytic anaemia"

- With sporadic haemolysis - "individuals are at risk of haemolysis in the presence of particular comorbidities, including infections, and vitamin B deficiency"

- With neonatal poikilocytosis - "individuals have a symptomatic haemolytic anaemia with poikilocytosis that resolves in the first year of life"

- With chronic haemolysis - " individual has a moderate to severe symptomatic haemolytic anaemia (this subtype has variable penetrance in some pedigrees)"

- With homozygosity or compound heterozygosity - "depending on the exact mutations involved, individuals may lie anywhere in the spectrum between having a mild haemolytic anaemia and having a life-threatening haemolytic anaemia with symptoms mimicking those of HPP (see below)"

- With pyropoikilocytosis (HPP) - "individuals are typically of African descent and have a life-threateningly severe haemolytic anaemia with micropoikilocytosis (small and misshapen erythrocytes) that is compounded by a marked instability of erythrocytes in even mildly elevated temperatures (pyropoikilocytosis is often found in burns victims and is the term is commonly used in reference to such people)

- South-east Asian ovalocytosis (SAO) (also called stomatocytic elliptocytosis) - "individuals are of South-East Asian descent (typically Malaysian, Indonesian, Melanesian, New Guinean or Filipino, have a mild haemolytic anaemia, and has increased resistance to malaria"

- Spherocytic elliptocytosis (also called hereditary haemolytic ovalocytosis) - "individuals are of European descent and elliptocytes and spherocytes are simultaneously present in their blood"

HPFH may alleviate the severity of certain hemoglobinopathies and thalassemias, and is selected for in populations with a high prevalence of these conditions (which in turn are often selected for in areas where malaria is endemic). Thus, it has been found to affect Americans of African and Greek descent.

The condition is usually asymptomatic, and is only noticed when screening for other hemoglobin disorders.

Administration of cytidine monophosphate and uridine monophosphate reduces urinary orotic acid and ameliorates the anemia.

Administration of uridine, which is converted to UMP, will bypass the metabolic block and provide the body with a source of pyrimidine.

Uridine triacetate is a drug approved by FDA to be used in the treatment of hereditary orotic aciduria.

In addition to the characteristic excessive orotic acid in the urine, patients typically have megaloblastic anemia (UMP synthase deficiency) which cannot be cured by administration of vitamin B12 or folic acid.

It also can cause inhibition of RNA and DNA synthesis and failure to thrive.

No treatment is indicated for essential fructosuria, while the degree of fructosuria depends on the dietary fructose intake, it does not have any clinical manifestations. The amount of fructose routinely lost in urine is quite small. Other errors in fructose metabolism have greater clinical significance. Hereditary fructose intolerance, or the presence of fructose in the blood (fructosemia), is caused by a deficiency of aldolase B, the second enzyme involved in the metabolism of fructose. This enzyme deficiency results in an accumulation of fructose-1-phosphate, which inhibits the production of glucose and results in diminished regeneration of adenosine triphosphate. Clinically, patients with hereditary fructose intolerance are much more severely affected than those with essential fructosuria, with elevated uric acid, growth abnormalities and can result in coma if untreated.

Genetic testing for the presence of mutations in protein molecules is considered to be a confirmatory testing technique. It is important to know the risks regarding the transmission and dangers of HPP.

Essential fructosuria is a genetic condition that is inherited in an autosomal recessive manner. Mutations in the "KHK" gene, located on chromosome 2p23.3-23.2 are responsible. The incidence of essential fructosuria has been estimated at 1:130,000. The actual incidence is likely higher, because those affected are asymptomatic.

Haematologists have identified a number of variants. These can be classified as below.

- Overhydrated hereditary stomatocytosis

- Dehydrated HSt (hereditary xerocytosis; hereditary hyperphosphatidylcholine haemolytic anaemia)

- Dehydrated with perinatal ascites

- Cryohydrocytosis

- 'Blackburn' variant.

- Familial pseudohyperkalaemia

There are other families that do not fall neatly into any of these classifications.

Stomatocytosis is also found as a hereditary disease in Alaskan malamute and miniature schnauzer dogs.

A normocytic anemia is defined as an anemia with a mean corpuscular volume (MCV) of 80–100 which is the normal range. However, the hematocrit and hemoglobin is decreased.

The issue is thought of as representing any of the following:

- a decreased production of normal-sized red blood cells (e.g., anemia of chronic disease, aplastic anemia);

- an increased production of HbS as seen in sickle cell disease (not sickle cell trait);

- an increased destruction or loss of red blood cells (e.g., hemolysis, posthemorrhagic anemia);

- an uncompensated increase in plasma volume (e.g., pregnancy, fluid overload);

- a B2 (riboflavin) deficiency

- a B6 (pyridoxine) deficiency

- or a mixture of conditions producing microcytic and macrocytic anemia.

Blood loss, suppressed production of RBCs or hemolysis represent most cases of normocytic anemia. In blood loss, morphologic findings are generally unremarkable except after 12 to 24 hrs where polychromasia appears. For reduced production of RBCs, like with low erythropoietin, the RBC morphology is unremarkable. Patients with disordered RBC production, e.g. myelodysplastic syndrome, may have a dual population of elliptocytes, teardrop cells, or other poikilocytes as well as a nucleated RBCs. Hemolysis will often demonstrate poikilocytes specific to a cause or mechanism. E.g. Bite cells and/or blistor cells for oxidative hemolysis, Acanthocytes for pyruvate kinase deficiency or McLeod phenotype, Sickle cells for sickle cell anemia, Spherocytes for immune-mediated hemolysis or hereditary spherocytosis, Elliptocytosis for iron deficiency or hereditary elliptocytosis and schistocytes for intravascular hemolysis. Many hemolytic anemias show multiple poikilocytes such as G6PD deficiency which may show blister and bites cells as well as shistocytes. Neonatal hemolysis may not follow the classic patterns as in adults

Mutations of the alphaspectrin gene causes this disease.

HPP can be considered as a subset of hereditary elliptocytosis to homozygous and it leads to severe disruption.