Most people do not have symptoms. It can cause a mild to moderate enlargement of the spleen, splenomegaly, as well as hemolytic anemia (which is the form of anemia due to abnormal breakdown of red blood cells prematurely). Too much hemoglobin C can reduce the number and size of red blood cells in the body, causing mild anemia. Occasionally, jaundice may occur. Some persons with this disease may develop gallstones that require treatment. Continued hemolysis may produce pigmented gallstones, an unusual type of gallstone composed of the dark-colored contents of red blood cells.

The presentation of individuals with alpha-thalassemia consists of:

Hemoglobin c (abbreviated as "Hb C" or "HbC") is an abnormal hemoglobin in which substitution of a glutamic acid residue with a lysine residue at the 6th position of the β-globin chain has occurred (E6K substitution).

Hemoglobin Lepore syndrome or Hb Lepore syndrome (Hb Lepore) is typically an asymptomatic hemoglobinopathy, which is caused by an autosomal recessive genetic mutation. The Hb Lepore variant, consisting of two normal alpha globin chains (HBA) and two deltabeta globin fusion chains which occurs due to a "crossover" between the delta (HBD) and beta globin (HBB) gene loci during meiosis and was first identified in an Italian family in 1958. There are three varieties of Hb Lepore, Washington (Hb Lepore Washington, AKA Hb Lepore Boston or Hb Lepore Washington-Boston), Baltimore (Hb Lepore Baltimore) and Hollandia (Hb Hollandia). All three varieties show similar electrophoretic and chromatographic properties and hematological findings bear close resemblance to those of the beta-thalassemia trait; a blood disorder that reduces the production of the iron-containing protein hemoglobin which carries oxygen to cells and which may cause anemia.

The homozygous state for Hb Lepore is rare. Patients of Balkan descent tend to have the most severe presentation of symptoms including severe anemia during the first five years of life. They also presented with significant splenomegaly, hepatomegaly, and skeletal abnormalities identical to those of homozygous beta-thalassemia. The amount of Hb Lepore in the patients blood ranged from 8 to 30%, the remainder being fetal hemoglobin (Hb F) which is present in minute quantities (typically<1 percent) in the red blood cells of adults. Known as F- cells they are present in a small proportion of overall RBCs.

Homozygous Hb Lepore is similar to beta-thalassemia major; however, the clinical course is variable. Patients with this condition typically present with severe anemia during the first two years of life. The heterozygote form is mildly anemic (Hb 11-13 g/dl) but presents with a significant hypochromia (deficiency of hemoglobin in the red blood cells) and microcytosis.

Alpha-thalassemia (α-thalassemia, α-thalassaemia) is a form of thalassemia involving the genes "HBA1" and "HBA2". Alpha-thalassemia is due to impaired production of alpha chains from 1, 2, 3, or all 4 of the alpha globin genes, leading to a relative excess of beta globin chains. The degree of impairment is based on which clinical phenotype is present (how many genes are affected).

Hemoglobin E or haemoglobin E (HbE) is an abnormal hemoglobin with a single point mutation in the β chain. At position 26 there is a change in the amino acid, from glutamic acid to lysine. Hemoglobin E is very common among people of Southeast Asian, Northeast Indian, Sri Lankan and Bangladeshi descent.

The βE mutation affects β-gene expression creating an alternate splicing site in the mRNA at codons 25-27 of the β-globin gene. Through this mechanism, there is a mild deficiency in normal β mRNA and production of small amounts of anomalous β mRNA. The reduced synthesis of β chain may cause β-thalassemia. Also, this hemoglobin variant has a weak union between α- and β-globin, causing instability when there is a high amount of oxidant. HbE can be detected on electrophoresis.

The diagnosis of Hb Lepore syndrome may be performed antenatally or postnatally via the use of a variety of tests

- Complete blood count (CBC)

- Cation Exchange High-performance liquid chromatography (CE-HPLC): a chromatographic technique used to separate and quantify various normal and abnormal hemoglobin components in blood.

- Hemoglobin electrophoresis

- DNA analysis:

Hemoglobin Barts, abbreviated Hb Barts, is an abnormal type of hemoglobin that consists of four gamma globins. It is moderately insoluble, and therefore accumulates in the red blood cells. It has an extremely high affinity for oxygen, resulting in almost no oxygen delivery to the tissues. As an embryo develops, it begins to produce alpha-globins at weeks 5-6 of development. When both HBA1 and HBA2, the two genes that code for alpha globins, are non-functional, only gamma globins are produced. These gamma globins bind to form hemoglobin Barts. It is produced in the disease alpha-thalassemia and in the most severe of cases, it is the only form of haemoglobin in circulation. In this situation, a fetus will develop hydrops fetalis and normally die before or shortly after birth, unless intrauterine blood transfusion is performed.

Since hemoglobin Barts is elevated in alpha thalassaemia, it can be measured, providing a useful screening test for this disease in some populations.

The ability to measure hemoglobin Barts makes it useful in newborn screening tests. If hemoglobin Barts is detected on a newborn screen, the patient is usually referred for further evaluation since detection of hemoglobin Barts can indicate either one alpha globin gene deletion, making the baby a silent alpha thalassemia carrier, two alpha globin gene deletions (alpha thalassemia), or hemoglobin H disease (three alpha globin gene deletions). Deletion of four alpha globin genes is not compatible with life.

This variant of hemoglobin is so called as it was discovered at St. Bartholomew's Hospital in London, also called St. Barts.

Signs of sickle cell disease usually begin in early childhood. The severity of symptoms can vary from person to person.

Sickle-cell disease may lead to various acute and chronic complications, several of which have a high mortality rate.

The terms "sickle-cell crisis" or "sickling crisis" may be used to describe several independent acute conditions occurring in patients with SCD. SCD results in anaemia and crises that could be of many types including the vaso-occlusive crisis, aplastic crisis, sequestration crisis, haemolytic crisis, and others. Most episodes of sickle-cell crises last between five and seven days. "Although infection, dehydration, and acidosis (all of which favor sickling) can act as triggers, in most instances, no predisposing cause is identified."

Hemoglobinopathy is a kind of genetic defect that results in abnormal structure of one of the globin chains of the hemoglobin molecule. Hemoglobinopathies are inherited single-gene disorders; in most cases, they are inherited as autosomal co-dominant traits. Common hemoglobinopathies include sickle-cell disease. It is estimated that 7% of world's population (420 million) are carriers, with 60% of total and 70% pathological being in Africa. Hemoglobinopathies are most common in populations from Africa, the Mediterranean basin and Southeast Asia.

Hemoglobinopathies imply structural abnormalities in the globin proteins themselves. Thalassemias, in contrast, usually result in underproduction of normal globin proteins, often through mutations in regulatory genes. The two conditions may overlap, however, since some conditions which cause abnormalities in globin proteins (hemoglobinopathy) also affect their production (thalassemia). Thus, some hemoglobinopathies are also thalassemias, but most are not.

Either hemoglobinopathy or thalassemia, or both, may cause anemia. Some well-known hemoglobin variants such as sickle-cell anemia and congenital dyserythropoietic anemia are responsible for diseases, and are considered hemoglobinopathies. However, many hemoglobin variants do not cause pathology or anemia, and thus are often not classed as hemoglobinopathies, because they are not considered pathologies. Hemoglobin variants are a part of the normal embryonic and fetal development, but may also be pathologic mutant forms of hemoglobin in a population, caused by variations in genetics. Other variants cause no detectable pathology, and are thus considered non-pathological variants.

Hemoglobin Hopkins-2 (Hb Hop-2) is a mutation of the protein hemoglobin, which is responsible for the transportation of oxygen through the blood from the lungs to the musculature of the body in vertebrates. Generally, the mutation causes two abnormal α chains in the protein's structure. Within the chains, the mutation is the result of hemoglobin's histidine amino acid being replaced with aspartic acid in the protein's genetic sequence. This amino acid structure change occurs at residue 112. Additionally, within one of the mutated alpha chains, there are substitutes at 114 and 118, two points on the amino acid chain. This mutation can cause sickle cell anemia.

Following the initial discovery of hemoglobin, two researchers working at Johns Hopkins Hospital in the mid-twentieth century, Ernest W. Smith and J.V. Torbert, discovered the Hopkins-2 mutation of hemoglobin. Work by Harvey A. Itano and Elizabeth A. Robinson in 1960 confirmed Smith's and Torbert's finding and emphasized the importance of the alpha loci in the mutation. Later in the twentieth century, Samuel Charache, another Hopkins affiliated scientist and doctor, studied the physiological impacts of the variant on health. His findings suggest that the variant plays no effect clinically.

Hemoglobin E disease results when the offspring inherits the gene for HbE from both parents. At birth, babies homozygous for the hemoglobin E allele do not present symptoms due to HbF (fetal hemoglobin) they still have. In the first months of life, fetal hemoglobin disappears and the amount of hemoglobin E increases, so the subjects start to have a mild β-thalassemia. People who are heterozygote for hemoglobin E (one normal allele and one abnormal allele) do not show any symptoms (there is usually no anemia or hemolysis). There are cases associated with haemolysis. Subjects homozygous for the hemoglobin E allele (two abnormal alleles) have a mild hemolytic anemia and mild enlargement of the spleen.

Iron-deficiency anemia is characterized by the sign of pallor (reduced oxyhemoglobin in skin or mucous membranes), and the symptoms of fatigue, lightheadedness, and weakness. None of these symptoms (or any of the others below) are sensitive or specific. Pallor of mucous membranes (primarily the conjunctiva) in children suggests anemia with the best correlation to the disease, but in a large study was found to be only 28% sensitive and 87% specific (with high predictive value) in distinguishing children with anemia [hemoglobin (Hb) <11.0 g/dl] and 49% sensitive and 79% specific in distinguishing severe anemia (Hb < 7.0 g/dl). Thus, this sign is reasonably predictive when present, but not helpful when absent, as only one-third to one-half of children who are anemic (depending on severity) will show pallor.

Because iron-deficiency anemia tends to develop slowly, adaptation occurs to the systemic effects that anemia causes, and the disease often goes unrecognized for some time. In severe cases, dyspnea can occur. Pica may also develop; pagophagia has been suggested to be "the most specific for iron deficiency."

Other possible symptoms and signs of iron-deficiency anemia include:

In general on alkaline electrophoresis in order of increasing mobility are hemoglobins A2, E=O=C, G=D=S=Lepore, F, A, K, J, Bart's, N, I, and H.

In general a sickling test (sodium bisulfite) is performed on abnormal hemoglobins migrating in the S location to see if the red cells precipitate in solution.

Iron-deficiency anemia is associated with poor neurological development, including decreased learning ability and altered motor functions. Causation has not been established, but there is a possible long-term impact from these neurological issues.

Anemia of chronic disease is usually mild but can be severe. It is usually normocytic, but can be microcytic. The presence of both anemia of chronic disease and dietary iron deficiency in the same patient results in a more severe anemia.

Anemia of prematurity refers to a form of anemia affecting preterm infants with decreased hematocrit.

While no single test is reliable to distinguish iron deficiency anemia from the anemia of chronic inflammation, there are sometimes some suggestive data:

- In anemia of chronic inflammation without iron deficiency, ferritin is normal or high, reflecting the fact that iron is sequestered within cells, and ferritin is being produced as an acute phase reactant. In iron deficiency anemia ferritin is low.

- Total iron-binding capacity (TIBC) is high in iron deficiency, reflecting production of more transferrin to increase iron binding; TIBC is low or normal in anemia of chronic inflammation.

Signs and symptoms of methemoglobinemia (methemoglobin level above 10%) include shortness of breath, cyanosis, mental status changes (~50%), headache, fatigue, exercise intolerance, dizziness and loss of hairlines.

Patients with severe methemoglobinemia (methemoglobin level above 50%) may exhibit seizures, coma and death (>70%). Healthy people may not have many symptoms with methemoglobin levels below 15%. However, patients with co-morbidities such as anemia, cardiovascular disease, lung disease, sepsis, or presence of other abnormal hemoglobin species (e.g. carboxyhemoglobin, sulfhemoglobin or sickle hemoglobin) may experience moderate to severe symptoms at much lower levels (as low as 5–8%).

Methemoglobinemia is a condition caused by elevated levels of methemoglobin in the blood. Methemoglobin is a form of hemoglobin that contains the ferric [Fe] form of iron. The affinity for oxygen of ferric iron is impaired. The binding of oxygen to methemoglobin results in an "increased" affinity for oxygen in the remaining heme sites that are in ferrous state within the same tetrameric hemoglobin unit. This leads to an overall reduced ability of the red blood cell to release oxygen to tissues, with the associated oxygen–hemoglobin dissociation curve therefore shifted to the left. When methemoglobin concentration is elevated in red blood cells, tissue hypoxia may occur.

There was a study on a three year old that was a carrier of the hemoglobin variant of Hopkins-2. The child had mild anemia and reticulocytosis, which is commonly seen in anemia. There were, however, no sickled cells found in the blood and they had no symptoms relating to sickle cell. There was also a reduced mean corpuscular volume (MCV), which is the average volume of red blood cell count.

Selenium deficiency in combination with Coxsackievirus infection can lead to Keshan disease, which is potentially fatal. Selenium deficiency also contributes (along with iodine deficiency) to Kashin-Beck disease. The primary symptom of Keshan disease is myocardial necrosis, leading to weakening of the heart. Kashin-Beck disease results in atrophy, degeneration and necrosis of cartilage tissue. Keshan disease also makes the body more susceptible to illness caused by other nutritional, biochemical, or infectious diseases.

Selenium is also necessary for the conversion of the thyroid hormone thyroxine (T4) into its more active counterpart, triiodothyronine, and as such a deficiency can cause symptoms of hypothyroidism, including extreme fatigue, mental slowing, goiter, cretinism, and recurrent miscarriage.

Selenium deficiency is relatively rare in healthy well-nourished individuals. Few cases in humans have been reported.

Signs of vitamin E deficiency include the following:

- Neuromuscular problems-such as spinocerebellar ataxia and myopathies.

- Neurological problems-may include dysarthria, absence of deep tendon reflexes, loss of the ability to sense vibration and detect where body parts are in three dimensional space, and positive Babinski sign.

- Hemolytic anemia-due to oxidative damage to red blood cells

- Retinopathy

- Impairment of the immune response

There is also some laboratory evidence that vitamin E deficiency can cause male infertility.