The American College of Obstetricians and Gynecologists recommends all people thinking of becoming pregnant be tested to see if they have thalassemia. Genetic counseling and genetic testing are recommended for families who carry a thalassemia trait.

A screening policy exists in Cyprus to reduce the rate of thalassemia, which, since the program's implementation in the 1970s (which also includes prenatal screening and abortion), has reduced the number of children born with the disease from one of every 158 births to almost zero.

In Iran as a premarital screening, the man's red cell indices are checked first, if he has microcytosis (mean cell hemoglobin < 27 pg or mean red cell volume < 80 fl), the woman is tested. When both are microcytic, their hemoglobin A2 concentrations are measured. If both have a concentration above 3.5% (diagnostic of thalassemia trait) they are referred to the local designated health post for genetic counseling.

Large scale awareness campaigns are being organized in India both by government and non-government organizations in favor of voluntary premarital screening to detect carriers of thalassemia and marriage between both carriers are strongly discouraged.

Diagnosis of alpha-thalassemia is primarily by laboratory evaluation and haemoglobin electrophoresis. Alpha-thalassemia can be mistaken for iron-deficiency anaemia on a full blood count or blood film, as both conditions have a microcytic anaemia. Serum iron and serum ferritin can be used to exclude iron-deficiency anaemia.

All beta thalassemias may exhibit abnormal red blood cells, a family history is followed by DNA analysis. This test is used to investigate deletions and mutations in the alpha- and beta-globin-producing genes. Family studies can be done to evaluate carrier status and the types of mutations present in other family members. DNA testing is not routine, but can help diagnose thalassemia and determine carrier status. In most cases the treating physician uses a clinical prediagnosis assessing anemia symptoms: fatigue, breathlessness and poor exercise tolerance. Further genetic analysis may include HPLC should routine electrophoresis prove difficult.

Abdominal pain due to hypersplenism and splenic infarction and right-upper quadrant pain caused by gallstones are major clinical manifestations. However, diagnosing thalassemiæ from symptoms alone is inadequate. Physicians note these signs as associative due to this disease's complexity. The following associative signs can attest to the severity of the phenotype: pallor, poor growth, inadequate food intake, splenomegaly, jaundice, maxillary hyperplasia, dental malocclusion, cholelithiasis, systolic ejection murmur in the presence of severe anemia and pathologic fractures. Based on symptoms, tests are ordered for a differential diagnosis. These tests include complete blood count; hemoglobin electrophoresis; serum transferrin, ferritin, total iron-binding capacity; urine urobilin and urobilogen; peripheral blood smear, which may show codocytes, or target cells; hematocrit; and serum bilirubin.

Thalassemia can coexist with other hemoglobinopathies. The most common of these are:

- Hemoglobin E/thalassemia: common in Cambodia, Thailand, and parts of India, it is clinically similar to β thalassemia major or thalassemia intermedia.

- Hemoglobin S/thalassemia: common in African and Mediterranean populations, is clinically similar to sickle-cell anemia, with the additional feature of splenomegaly.

- Hemoglobin C/thalassemia: common in Mediterranean and African populations, hemoglobin C/β thalassemia causes a moderately severe hemolytic anemia with splenomegaly; hemoglobin C/β thalassemia produces a milder disease.

- Hemoglobin D/thalassemia: common in the northwestern parts of India and Pakistan (Punjab region).

Those homozygous (Hb LeporeLepore; a very rare situation) or compound heterozygous (Hb Lepore-Β-thalassaemia) might suffer from a severe anaemia. They should be managed in a comprehensive multi-disciplinary program of care. Management includes a regular course of blood transfusions, although the clinical severity in compound (double) heterozygotes can range from minor to major, depending on the combination of genes that have caused the condition.

A potential complication that may occur in children that suffer acute anemia with a hemoglobin count below 5.5 g/dl is silent stroke A silent stroke is a type of stroke that does not have any outward symptoms (asymptomatic), and the patient is typically unaware they have suffered a stroke. Despite not causing identifiable symptoms a silent stroke still causes damage to the brain, and places the patient at increased risk for both transient ischemic attack and major stroke in the future.

Treatment for alpha-thalassemia may consist of blood transfusions, and possible splenectomy; additionally, gallstones may be a problem that would require surgery. Secondary complications from febrile episode should be monitored, and most individuals live without any need for treatment

Additionally, stem cell transplantation should be considered as a treatment (and cure), which is best done in early age. Other options, such as gene therapy, are still being developed.

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.

First degree relatives of those with primary haemochromatosis should be screened to determine if they are a carrier or if they could develop the disease. This can allow preventive measures to be taken.

Screening the general population is not recommended.

There were five carriers of Hemoglobin Hopkins 2 in the Fuller-Carr family and ten double heterozygotes of Ho-2 and Hemoglobin S. All the carriers were in good health and had normal hematology test results. Out of those carrying hemoglobin S and Ho-2, none were anemic; but, a few of those studied displayed elevated reticulocyte counts. This is measured through a blood test that analyzes the speed of production of red blood cells by bone marrow and its release into the blood. There was no suggestion of symptomatic sickle cell anemia in the family.

There are several methods available for diagnosing and monitoring iron loading including:

- Serum ferritin: In males and postmenopausal females, a serum ferritin value of over 300 ng/mL (670 pmol/L) indicates iron overload. In premenopausal females, a serum ferritin value of over 150 or 200 ng/mL (330 or 440 pmol/L) indicates iron overload.

- Liver biopsy

- HFE

- MRI

Serum ferritin testing is a low-cost, readily available, and minimally invasive method for assessing body iron stores. However, the major problem with using it as an indicator of iron overload is that it can be elevated in a range of other medical conditions unrelated to iron levels including infection, inflammation, fever, liver disease, kidney disease, and cancer. Also, total iron binding capacity may be low, but can also be normal.

The standard of practice in diagnosis of haemochromatosis was recently reviewed by Pietrangelo. Positive HFE analysis confirms the clinical diagnosis of haemochromatosis in asymptomatic individuals with blood tests showing increased iron stores, or for predictive testing of individuals with a family history of haemochromatosis. The alleles evaluated by HFE gene analysis are evident in ~80% of patients with haemochromatosis; a negative report for HFE gene does not rule out haemochromatosis. In a patient with negative HFE gene testing, elevated iron status for no other obvious reason, and family history of liver disease, additional evaluation of liver iron concentration is indicated. In this case, diagnosis of haemochromatosis is based on biochemical analysis and histologic examination of a liver biopsy. Assessment of the hepatic iron index (HII) is considered the "gold standard" for diagnosis of haemochromatosis.

Magnetic resonance imaging (MRI) is emerging as a noninvasive alternative to accurately estimate iron deposition levels in the liver as well as heart, joints, and pituitary gland.

The serum iron and total iron-binding capacity (transferrin) are helpful but not diagnostic; it is quiet possible to have co-existing ineffective iron utilisation and iron deficiency, as determined by bone marrow iron status, e.g. in rheumatoid arthritis.

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.

1- Secondary anaemias

- Chronic infection/inflammation

- Malignancy

2- Thalassaemia

3- Sideroblastic anaemia

The diagnosis of this condition can be done via the following:

- Flow cytometry

- Bleeding time analysis

Hemoglobin Constant Spring is a variant of Hemoglobin in which a mutation in the alpha globin gene produces an alpha globin chain that is abnormally long. It is the most common nondeletional alpha-thalassemia mutation associated with hemoglobin H disease. The quantity of hemoglobin in the cells is low because the messenger RNA is unstable and some is degraded prior to protein synthesis. Another reason is that the Constant Spring alpha chain protein is itself unstable. The result is a thalassemic phenotype.

Hemoglobin Constant Spring is renamed after Constant Spring district in Jamaica.

A diagnosis is made by measuring the enzymatic activity of alpha--mannosidase in white blood cells. If there is a decreased level of the enzyme in comparison to standard levels, a diagnosis can be made. It is thought that this disorder might be under-diagnosed for a few different reasons—the diagnosis is often made late in the disease's progression, symptoms are often mild, or the biochemical diagnosis does not yield conclusive results.

The life expectancy in alpha-mannosidosis is highly variable. Individuals with early onset severe disease often do not survive beyond childhood, whereas those with milder disorders may survive well into adult life.

Amniocentesis or chorionic villus sampling can be used to screen for the disease before birth. After birth, urine tests, along with blood tests and skin biopsies can be used to diagnose Schindler disease. Genetic testing is also always an option, since different forms of Schindler disease have been mapped to the same gene on chromosome 22; though different changes (mutations) of this gene are responsible for the infantile- and adult-onset forms of the disease.

A1AT deficiency remains undiagnosed in many patients. Patients are usually labeled as having COPD without an underlying cause. It is estimated that about 1% of all COPD patients actually have an A1AT deficiency. Thus, testing should be performed for all patients with COPD, asthma with irreversible airflow obstruction, unexplained liver disease, or necrotizing panniculitis. The initial test performed is serum A1AT level. A low level of A1AT confirms the diagnosis and further assessment with A1AT protein phenotyping and A1AT genotyping should be carried out subsequently. The Alpha-1 Foundation offers free, confidential testing.

As protein electrophoresis does not completely distinguish between A1AT and other minor proteins at the alpha-1 position (agarose gel), antitrypsin can be more directly and specifically measured using a nephelometric or immunoturbidimetric method. Thus, protein electrophoresis is useful for screening and identifying individuals likely to have a deficiency. A1AT is further analyzed by isoelectric focusing (IEF) in the pH range 4.5-5.5, where the protein migrates in a gel according to its isoelectric point or charge in a pH gradient.

Normal A1AT is termed M, as it migrates toward the center of such an IEF gel. Other variants are less functional and are termed A-L and N-Z, dependent on whether they run proximal or distal to the M band. The presence of deviant bands on IEF can signify the presence of alpha-1 antitrypsin deficiency. Since the number of identified mutations has exceeded the number of letters in the alphabet, subscripts have been added to most recent discoveries in this area, as in the Pittsburgh mutation described above. As every person has two copies of the A1AT gene, a heterozygote with two different copies of the gene may have two different bands showing on electrofocusing, although a heterozygote with one null mutant that abolishes expression of the gene will only show one band. In blood test results, the IEF results are notated as, e.g., PiMM, where Pi stands for protease inhibitor and "MM" is the banding pattern of that person.

Other detection methods include use of enzyme-linked-immuno-sorbent-assays in vitro and radial immunodiffusion.

Alpha 1-antitrypsin levels in the blood depend on the genotype. Some mutant forms fail to fold properly and are, thus, targeted for destruction in the proteasome, whereas others have a tendency to polymerize, thereafter being retained in the endoplasmic reticulum. The serum levels of some of the common genotypes are:

- PiMM: 100% (normal)

- PiMS: 80% of normal serum level of A1AT

- PiSS: 60% of normal serum level of A1AT

- PiMZ: 60% of normal serum level of A1AT

- PiSZ: 40% of normal serum level of A1AT

- PiZZ: 10-15% (severe alpha-1 antitrypsin deficiency)

The majority of patients is initially screened by enzyme assay, which is the most efficient method to arrive at a definitive diagnosis. In some families where the disease-causing mutations are known and in certain genetic isolates, mutation analysis may be performed. In addition, after a diagnosis is made by biochemical means, mutation analysis may be performed for certain disorders.

Infants with Schindler disease tend to die within 4 years of birth, therefore, treatment for this form of the disease is mostly palliative. However, Type II Schindler disease, with its late onset of symptoms, is not characterized by neurological degeneration. There is no known cure for Schindler disease, but bone marrow transplants have been trialed, as they have been successful in curing other glycoprotein disorders.

Hemoglobin J is an abnormal hemoglobin, an alpha globin gene variant and present in various geographic locations. It was first reported in a black American family in 1956. Later on reported from Indonsia, India, and other parts of the world. Hemoglobin J reported from Meerut India shows the mutation of 120th Alanine to Glutamic acid on alpha chain. Hemoglobin J was also reported from Chhattisgarh, Central India as revealed by Lingojwar and coworkers in 2016.

In addition to genetic tests involving "PEX" genes, biochemical tests have proven highly effective for the diagnosis of infantile Refsum disease and other peroxisomal disorders. Typically, IRD patients show elevated very long chain fatty acids in their blood plasma. Cultured primarily skin fibroblasts obtained from patients show elevated very long chain fatty acids, impaired very long chain fatty acid beta-oxidation, phytanic acid alpha-oxidation, pristanic acid alpha-oxidation, and plasmalogen biosynthesis.