The two types of alpha thalassemia, hydrops fetalis and Hemoglobin H disease, are the ones that lead to observable symptomatology amongst the various types of alpha thalassemia; this is due to the extremely diminished concentration of functional hemoglobin [6].

Embryos with hydrops fetalis experience death in utero or shortly after birth, if their condition is not diagnosed in advance. Typical findings include hepatomegaly, splenomegaly, profound anemia, edema and an extremely decreased cardiac output. Expectant mothers also experience pregnancy complications, when carrying an embryo with hydrops fetalis. Preeclampsia, premature labor, oligo- or polyhydramnios are common issues accompanying such a pregnancy.   

With regard to Hemoglobin H disease, symptomatology is individualized. Patients may be diagnosed at any point between childhood and adulthood and some may even be asymptomatic at the time of diagnosis. Hemolytic anemia is the primary finding (hypochromic microcytic), accompanied by splenomegaly and occasional hepatomegaly, jaundice and some facial skeletal defects, such as hypertrophic maxilla. The administration of drugs that cause oxidative stress exacerbates the hemolytic phenomena in patients with HbH disease, who may also display hypersplenism as a reaction. 

• Splenomegaly

  They more frequently have splenomegaly and severe anemia with febrile illnesses and viral infections, often requiring transfusion. If anemia is chronically severe and the child has splenomegaly, a splenectomy may be performed. [thalassemia.com]

  Symptoms and signs result from anemia, hemolysis, splenomegaly, bone marrow hyperplasia, and, if there have been multiple transfusions, iron overload. Diagnosis is based on genetic tests and quantitative Hb analysis. [msdmanuals.com]

  Patients with Hb H disease often have symptomatic hemolytic anemia and splenomegaly. [merckmanuals.com]

  Three deletions: Hb H Disease Patients with three alpha-globin deletions display a symptomatic microcytic anemia with moderate extravascular hemolysis that may yield splenomegaly. [pathwaymedicine.org]

• Anemia

  Thalassemia Thalassemia includes a number of different forms of anemia (red blood cell deficiency). [meddean.luc.edu]

  During pregnancy, the microcytic anemia can be mistaken for anemia of pregnancy. The individual with α thalassemia trait will experience no significant health problems except a possible slight anemia which cannot be treated with iron. [thalassemia.com]

  Possible causes include alpha thalassemia, iron deficiency, sideroblastic anemia, anemia of chronic disease and lead poisoning. [symptoma.com]

  Additional signs and symptoms can include severe anemia, an enlarged liver and spleen (hepatosplenomegaly), heart defects, and abnormalities of the urinary system or genitalia. [rxlist.com]

• Fatigue

  In alpha-thalassemia major, people have moderate or severe symptoms of anemia, including fatigue, shortness of breath, paleness, and an enlarged spleen, which leads to a feeling of fullness and abdominal discomfort. [merckmanuals.com]

  Thalassemia can cause anemia, leaving you fatigued. If you have mild thalassemia, you might not need treatment. But more severe forms might require regular blood transfusions. [mayoclinic.org]

  With thalassemia, the red blood cells are destroyed at a faster rate, leading to anemia, a condition that can cause fatigue and other complications. [m.kidshealth.org]

  Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications. What are the types of alpha thalassemia? Two types of alpha thalassemia can cause health problems. [rxlist.com]

• Vascular Disease

  […] in Diagnosis and Treatment of Special Diseases (Tehran, November 2006), Cardio-vascular Diseases in Diabetes (Tehran, August 2008), and International Workshop on Advanced Diagnosis on Genetic Diseases (Tehran, March 2007). en The National Thalassaemia [ar.glosbe.com]

  This is one explanation for thrombotic and vascular complications in this population and they may be useful markers to follow in vascular disease. [clinicaladvisor.com]

  Coller, MD, David Rockefeller Professor of Medicine; Head, Allen and Frances Adler Laboratory of Blood and Vascular Diseases, The Rockefeller University, for assistance in the preparation of this report. [rarediseases.org]

• Heart Disease

  Furthermore, specialized imaging tests can now find iron in the heart and allow patients to be treated before they develop iron-related heart failure. [hematology.org]

  If adequately transfused, children will develop normally, but will develop secondary hemochromatosis and die of heart disease in their 20s. [lecturio.com]

  Roberta Keller is a neonatologist, an expert in caring for critically ill newborns, particularly those with congenital lung or heart disease. [thalassemia.com]

  In one case, the final autopsy diagnosis was incorrectly ascribed to congenital heart disease. In another case, the woman later became pregnant again and was found to have an affected fetus again in the 24th week of the second pregnancy. [bloodjournal.org]

• Jaundice

  Some people have jaundice and abdominal fullness or discomfort. Diagnosis usually requires special hemoglobin tests. Mild thalassemia may not require treatment, but severe thalassemia may require bone marrow transplantation. [merckmanuals.com]

  Hemoglobin H (HbH) disease, resulting from three of four alpha globin genes being nonfunctional, is characterized by microcytic hypochromic hemolytic anemia, hepatosplenomegaly, mild jaundice, and sometimes thalassemia-like bone changes. [meddean.luc.edu]

  Symptoms In alpha thalassemia there can be no symptoms or in severe cases hemolytic anemia and an enlarged spleen, paleness, jaundice, and fatigue. [differencebetween.net]

  BACKGROUND: Hereditary spherocytosis (HS) is a common inherited hemolytic anemia characterized by heterogeneous clinical presentations with variable degrees of anemia, jaundice, splenomegaly and gallstones. [ncbi.nlm.nih.gov]

  This disease results in anemia, an enlarged spleen, and mild jaundice. Most individuals are mildly disabled by this condition. Some people with more severe disease require frequent blood transfusions. [sema4.com]

• Hepatomegaly

  Concurrent alpha thalassemia might be a protective trait against significant hepatomegaly in sickle cell anaemia patients more than 60 months of age at Mulago hospital. [ncbi.nlm.nih.gov]

  Placentomegaly and increased placental thickness, increased cardiothoracic ratio, ascites and hepatomegaly in the fetus aids in the diagnosis. [medicaljoyworks.com]

  Hemolytic anemia is the primary finding (hypochromic microcytic), accompanied by splenomegaly and occasional hepatomegaly, jaundice and some facial skeletal defects, such as hypertrophic maxilla. [symptoma.com]

  Hepatomegaly is not a common finding and there may be some association with mental retardation. Due to the hemolytic nature of this anemia, there may be an increase in respiratory infections, leg ulcers and gallstones. [labce.com]

• Fracture

  The long bones in the arms and legs may weaken and fracture easily. Children who have beta-thalassemia major may grow more slowly and reach puberty later than they normally would. [merckmanuals.com]

  […] of the spine (which may result in cord compression or other neurologic deficits) Osteopenia and fractures Splenectomy or transfusional support is often necessary in the second or third decade of life. [emedicine.medscape.com]

  This results in swelling of the spleen and eventually abdominal swelling (enlargement) Bone abnormalities, such as swelling and fractures, may occur due to the compensatory expansion of bone marrow Jaundice and dark urine results from the breakdown of [dovemed.com]

  Faisalabad histiocytosis mimics Rosai-Dorfman disease: brothers with lymphadenopathy, intrauterine fractures, short stature, and sensorineural deafness. Pediatr Blood Cancer 2006; 47(5): 629–632. Google Scholar 3. [journals.sagepub.com]

  Bone pain and fragility fractures Caused by two major mechanisms: Destruction of the cortex leading to weakening of the bone Secondary to Osteopenia/osteoporosis (mechanism above) Cardiac failure and arrhythmias Secondary to anemia and iron overload Splenomegaly [pathophys.org]

• Ulcer

  The average of severe vaso-occlusive crises, the rates of blood transfusions per year, the rate of osteonecrosis, cholelithiasis and leg ulcers were significantly lower in the group of patients with α 3.7 homozygous deletion and α 3.7 triplication. [ncbi.nlm.nih.gov]

  In beta-thalassemia major (sometimes called Cooley anemia), people have severe symptoms of anemia, such as fatigue, weakness, and shortness of breath, and they may also have jaundice, causing yellowing of the skin and whites of the eyes, skin ulcers, [merckmanuals.com]

  Due to the hemolytic nature of this anemia, there may be an increase in respiratory infections, leg ulcers and gallstones. Skeletal changes are not commonly seen in hemoglobin H disease. [labce.com]

  There should be ongoing monitoring of growth, bone health, spleen size, inflammation of the gallbladder, leg ulcers and fatigue. Blood transfusions, or removal of the spleen or gallbladder may be indicated. [thinkgenetic.com]

  Uncommon occurrences in a child with Hgb H would be severe anemia, skin ulceration, and splenomegaly requiring splenectomy. Unlike individuals who have beta thalassemia, hemosiderosis is rare in Hgb H disease. [thalassemia.com]

• Skin Ulcer

  In beta-thalassemia major (sometimes called Cooley anemia), people have severe symptoms of anemia, such as fatigue, weakness, and shortness of breath, and they may also have jaundice, causing yellowing of the skin and whites of the eyes, skin ulcers, [merckmanuals.com]

  Uncommon occurrences in a child with Hgb H would be severe anemia, skin ulceration, and splenomegaly requiring splenectomy. Unlike individuals who have beta thalassemia, hemosiderosis is rare in Hgb H disease. [thalassemia.com]

  Detailed Description: Many of the complications of sickle cell disease, such as stroke, kidney damage, skin ulceration,pulmonary hypertension, and cardiac hypertrophy are prevented, delayed or reduced by inheritance of one of more deletions of the alpha [clinicaltrials.gov]

• Hydrops Fetalis

  Hydrops fetalis is a condition that results from a four-gene deletion. [stjude.org]

  Individuals with HbH disease or hydrops fetalis, both alpha-thalassemia subcategories, experience severe medical problems. [symptoma.com]

  The more severe type is known as hemoglobin Bart hydrops fetalis (or Hb Bart) syndrome; the milder form is called HbH disease. No treatment is effective for Hb Bart hydrops fetalis. [genomicseducation.hee.nhs.uk]

  HEMOGLOBIN (Hb) BART’S HYDROPS FETALIS Hb Bart’s hydrops fetalis, also known as alpha thalassemia major, is the most severe form of alpha thalassemia. [rarediseases.org]

  Hb Bart syndrome is characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. [rxlist.com]

• Frontal Bossing

  bossing (due to bone marrow expansion) Delayed pneumatization of sinuses Marked overgrowth of the maxillae Ribs and long bones becoming boxlike and convex Premature closure of epiphyses resulting in shortened limbs Compression fracture of the spine [emedicine.medscape.com]

  Bony deformities (frontal bossing, prominent facial bones, and dental malocclusion). Marked pallor and slight to moderate jaundice. Exercise intolerance, cardiac flow murmur or heart failure secondary to severe anaemia. [patient.info]

• Stroke

  Stroke was reported in eight cases (7.4%). Benin haplotype was the most prevalent (66.3%; n = 208 chromosomes). [journals.plos.org]

  Detailed Description: Many of the complications of sickle cell disease, such as stroke, kidney damage, skin ulceration,pulmonary hypertension, and cardiac hypertrophy are prevented, delayed or reduced by inheritance of one of more deletions of the alpha [clinicaltrials.gov]

  More distinctive symptoms of this form include thrombosis of the deep veins, presenting as: leg thrombosis portal vein thrombosis stroke or embolism. These are more common in the intermediate form as compared to the major form. [news-medical.net]

  The report involved three groups of children with sickle cell anemia, including one group with cerebral vasculopathy (ie, stroke, silent infarct, or abnormal transcranial Doppler ultrasonography results), a second group without cerebral vasculopathy, [emedicine.medscape.com]

Thalassemia is diagnosed via laboratory tests and specifically a complete blood count, serum ferritin, hemoglobin electrophoresis and a peripheral smear. Hypochromic microcytic anemia is the primary finding in tests of individuals with thalassemia; the severity depends on the type of thalassemia. 

Differential diagnosis is extensive when hypochromic microcytic anemia is discovered. Possible causes include alpha thalassemia, iron deficiency, sideroblastic anemia, anemia of chronic disease and lead poisoning. The following observations are useful tools in order to distinguish thalassemia from the other possible causes:

•  Mean corpuscular volume (MCV): Patients with thalassemia usually exhibit an MCV< 75 fl. Anemia that is a result of iron deficiency usually leads to an MCV> 80 fl.
• Red cell distribution width (RDW): Over 90% of the cases of iron deficiency anemia exhibit an increased RDW. Contrary to that, only half of the patients with thalassemia have an augmented RDW.
• Mentzer index: The Mentzer index is the ratio of MCV/red blood cell count. It is >13 in patients affected by iron deficiency anemia and <13 in patients that have inherited thalassemia [4] [5].

• Enlargement of the Liver

  The fetus can also have other problems including severe anemia, enlargement of the liver and spleen (hepatosplenomegaly), and defects in the heart, urinary system, or genitals. [stanfordchildrens.org]

  However, there is severe anemia with complications including progressive enlargement of the liver, spleen and heart and malformation of bones. [medicinenet.com]

  Other symptoms include: poor growth pallor jaundice enlargement of the liver and spleen due to the breakdown of red cells containing the abnormal hemoglobin leg ulcers bone changes secondary to marrow expansion the appearance of other masses due to the [news-medical.net]

  […] with Alpha Thalassemia are also at an increased risk for breaking (fracturing) bones due to a weakened skeletal system They are also at an increased risk of developing an enlarged spleen and liver. [dovemed.com]

• Microcytic Anemia

  The aim of this study was to determine alpha thalassemia mutations in patients with unsolved hypochromic microcytic anemia and to evaluate types of mutations. [ncbi.nlm.nih.gov]

  During pregnancy, the microcytic anemia can be mistaken for anemia of pregnancy. The individual with α thalassemia trait will experience no significant health problems except a possible slight anemia which cannot be treated with iron. [thalassemia.com]

  Two deletions: Alpha-thalasemia Minor Patients with two alpha-globin deletions are still asymptomatic but typically display a microcytic anemia on laboratory examination. [pathwaymedicine.org]

  Full blood count Hb H disease will show microcytic anemia with MCV less than 75 fl. Thalassemia trait may have mild microcytic anemia. Full blood count Hb H disease will show microcytic anemia with MCV less than 75 fl. [medicaljoyworks.com]

• Anisopoikilocytosis

  Histologic Findings Peripheral blood smear may reveal target cells, microcytosis, hypochromia, and anisopoikilocytosis. [emedicine.medscape.com]

  […] utero or shortly after birth) References:[11][1][2][12] Diagnostics Laboratory tests Blood sample Microcytic hypochromic anemia Signs of hemolysis (↓ haptoglobin, ↑ LDH, ↑ indirect bilirubin, ↑ reticulocytes) Blood smear: target cells;, teardrop cells;, anisopoikilocytosis [amboss.com]

  Most individuals with HbH disease, thalassemia trait and carriers are clinically well and survive without any treatment (GeneReviews 2005: NBK1435) Peripheral smear description Hb Bart's hydrops fetalis syndrome: Large, hypochromic red cells and severe anisopoikilocytosis [pathologyoutlines.com]

  Peripheral smear shows target cells, teardrop RBCs, polychromasia, moderate anisopoikilocytosis, and basophilic stippling. Hemoglobin electrophoresis is normal in alpha thalassemia minima and minor. [clinicaladvisor.com]

• Thrombocytosis

  […] expected with primary thrombocytosis. [academic.oup.com]

  If splenectomy is anticipated, the complication of severe post-splenectomy thrombocytosis with hypercoagulability can occur, leading to thrombosis of the splenic vein or hepatic veins. [thalassemia.com]

  Post-splenectomy patients with marked thrombocytosis should also be started on low-dose aspirin. [clinicaladvisor.com]

• Erythrocytosis

  The molecular defect for erythrocytosis was detected together with the rare Hb Olympia (HBB:c.61G>A) variant. [ncbi.nlm.nih.gov]

  Individuals who have alpha thalassemia trait are identified by microcytosis, erythrocytosis, hypochromia, and mild anemia. [thalassemia.com]

  This test can also identify alpha globin variants that can result in variable phenotypes, such as erythrocytosis, chronic hemolytic anemia, and many that are clinically benign. [mayocliniclabs.com]

  Individuals who have alpha thalassaemia trait are identified by microcytosis, erythrocytosis, hypochromia and mild anaemia. [nhsggc.org.uk]

• Hemoglobin Decreased

  Definition / general Alpha thalassemia is a group of inherited blood disorders characterized by reduced or absent production of α-globin subunits, resulting in low levels of hemoglobin, decreased mean corpuscular volume (MCV) and decreased mean corpuscular [pathologyoutlines.com]

  Introduction Thalassemia is a general term for a group of congenital, genetic disorders characterized by low levels of hemoglobin, decreased red blood cell production, and anemia. [rarediseases.org]

• Hepatocellular Carcinoma

  Hepatocellular carcinoma in thalassaemia: an update of the Italian Registry. Br J Haematol. 2014;167:121–6. [ncbi.nlm.nih.gov]

  With increasing length of survival, hepatocellular carcinoma is becoming an increasing problem. [ 15 ] Desferrioxamine can cause toxicity: Local reaction at the site of injection can be severe. [patient.info]

  Concomitant viral hepatitis poses further increased risk of hepatocellular carcinoma and cirrhosis. Most thalassemia patients older than 25 years are infected with hepatitis C (HCV). [clinicaladvisor.com]

  Hepatocellular carcinoma in the thalassaemia syndromes. Br J Haematol. Jan 2004;124(1):114-7. [Medline]. Cao A, Rosatelli C, Galanello R, et al. The prevention of thalassemia in Sardinia. Clin Genet. Nov 1989;36(5):277-85. [Medline]. [wikirefua.org.il]

Treatment of alpha thalassemia is individualized and depends on the type of the condition an individual suffers from. Mild cases of thalassemia that cause no clinical disturbance or profound laboratory findings may be simply monitored, without any treatment. On the other hand, markedly low levels of hemoglobin may be an indicator of treatment initiation: extremely low hemoglobin levels usually require transfusions for the whole of the patient's life, whereas surgical intervention is reserved for some patients [7] [8] [9]. Individuals with low levels of iron and/or folic acid may also require the administration of supplements.

General supportive care

Hemoglobin abnormalities usually need supportive care in patients with HbB disease. Blood transfusions are not conducted in fixed intervals, but rather when the patient displays markedly low levels of hemoglobin caused by acute HbH episodes, infections, etc [10] [11]. Transfusions can be initiated as soon as the first days of a neonate's life.

Patients generally need a few transfusion sessions throughout their lives, as hemoglobin levels fluctuate between the values of 7 to 10 g/dL. However, severer cases with hemoglobin levels constantly below 7 g/dL may need lifelong transfusions, which renders the patient susceptible to the complication of iron overload. To prevent this, chelation therapy is implemented. Iron chelation therapy may be necessary even for patients who do not receive a great number of transfusions. In patients affected by HbH, hemolysis is caused by various infections or the use of drugs.

Iron and folic acid

Patients with alpha thalassemia must be closely monitored to detect a possible iron deficiency, for which they may be treated with iron supplements if necessary, although this treatment does not lead to improved blood test results. Special attention should also be drawn to the fact that, many individuals who display low levels of iron, actually suffer from hemochromatosis, which implies that excessive amounts of iron have accumulated within organs and tissue. If a patient is found to have raised levels of ferritin, its consumption should be restricted in the diet. Lastly, a patient may also receive folic acid supplements, particularly if they display increased levels of reticulocytes.

Surgical intervention

Splenectomy may be a measure taken to address cases of patients with HbH, complicated with hypersplenism. Erythroid hyperplasia, when present, can also induce skeletal irregularities, which can be corrected with surgery, dental or orthopedic. 

Additional treatment options

After a splenectomy has been performed, patients are susceptible to various infections and should therefore be cautious and vaccinate themselves against pathogens , such as pneumococcus. As a last resort, allogeneic hematopoietic stem cell transplantation can be an option, but is reserved for extremely severe cases with no response to other treatment plans, due to the increased mortality and morbidity accompanying the procedure.

The prognosis depends on the type of thalassemia a patient suffers from. Individuals with the alpha thalassemia trait and silent carriers are clinically unaffected by the condition and require no treatment. Patients with HbH disease face a comprehensively good prognosis too, although each case is individualized, with complications varying. 

Embryos that are diagnosed with hydrops fetalis, which implies the complete absence of functional alpha genes, are in need of transfusions in utero, so that they can survive past birth. Blood transfusions have to be continued for the whole of the individual's life, as they are unable to produce functional hemoglobin of any type. This type of treatment renders it possible for patients with hydrops fetalis to live longer than before, but complications pose a significant danger: frequent transfusions lead to the accumulation of excessive iron in the organs of the body and heart dysfunction. Diabetes mellitus and various abnormalities of the endocrine glands are also observed in patients with alpha thalassemia major [4] [5].

Alpha thalassemia is a group of genetic conditions. The primary abnormality that leads to the particular genotype includes deletions of the alpha globin genes, or deletions of the non-coding DNA that regulates their transcription (regulatory elements) and may be found either on the same chromosome or on a different one. Deletion, however, is not the only type of mutation that can lead to alpha thalassemic syndromes: nonsensical mutations, frame shifts, point mutations and chain termination mutations have been detected, which can also be located in the regions adjacent to the alpha globin gene. The editing of the nascent pre-messenger RNA transcript (splicing) may be subsequently impaired, the initiation of mRNA translation may be prevented and various other disruptions can result in alpha thalassemic anemia [1].

Countries located in the tropical zones and adjacent regions display a high prevalence of alpha thalassemia, with the population carrying the gene at a rate of nearly 90% in some occasions. Specifically, the subcategory of HbH disease is most commonly observed in Southeast Asia, the Mediterranean and the Middle East, whereas hydrops fetalis is most prevalent in Southeast Asia. It is believed that the simultaneous high frequency of alpha thalassemia in tropical regions is a result of the natural selection process: the mutation offers some protection against malaria, also prevalent in those locations, and it has been selected during the evolution process, because it enhances the individuals' prospects of survival. Migration and the subsequent redistribution of the world's population have led to the presence of alpha thalassemia in regions of America or North Europe [5].

Alpha thalassemia is a direct result of diminished alpha-chain production. The excessive amounts of beta chains lead to a lack of molecular stability and to an insoluble hemoglobin compound that forms Heinz bodies within the cell (insoluble inclusions). Heinz bodies exert further pressure and damage the membrane of the red blood cells. Due to the red blood cells' inability to produce adequate amounts of fully functional hemoglobin, the cells are hypochromic and relatively smaller in size, when compared with healthy red cells [5]. Depending on the result of the genetic mutation, the following alpha thalassemic syndromes have been described:

• Alpha (0) thalassemia
• Alpha (+) thalassemia
• Silent carrier
• Trait of alpha thalassemia
• Hemoglobin H disease (HbH)

Alpha(0) thalassemia

Alpha (0) thalassemia is a subcategory of alpha thalassemia, involving the complete dysfunction of both genes encoding for the alpha globin (--/--). A patient with this genetic abnormality does not have the ability to synthesize any of the hemoglobin types and usually dies before birth or shortly after. It is the most severe type of alpha thalassemia and is otherwise referred to as hydrops fetalis or hemoglobin Bart's. Currently, over twenty different mutations have been discovered, that account for alpha (0) thalassemia. 

Alpha(+) thalassemia

Alpha (+) thalassemia is a wider category of disease type and encompasses the silent carrier, alpha thalassemia trait and hemoglobin H types. Patients display diminished production of alpha globin, but possess at least one functional alpha gene.

The silent carrier type is the mildest form of alpha (+) thalassemia. The patients possess three functional alpha genes (-α/αα) and in the majority of the cases exhibit no abnormal findings in a standard blood test. The mean corpuscular volume (MVC) and mean corpuscular hemoglobin (MCH) might be slightly affected sometimes.

On the other hand, patients with the trait of alpha thalassemia possess two functional alpha genes, either in the pattern of (-α/-α) or (--/αα). Patients suffer from mild anemia, with a red blood count greater than 5.5 x 1012/L. Their MCH and MCV are also affected.

Finally, the most severe type of alpha (+) thalassemia is the HbH disease (Hemoglobin H disease. Patients have one functional alpha gene (-α/--); as a result, the beta globin chains greatly predominate is the structure of the red blood cells and these beta chains are conjoined in masses. This type of abnormal hemoglobin constitutes up to 1/3 of the total hemoglobin of the patient. Hemolytic phenomena are common when oxidative agents (e.g sulfonamide) are administered to these patients, due to the erythrocytes' increased sensitivity. Furthermore, the conjunction of HbH increases as the erythrocytes age: this results in their early destruction, as they are recognized as dysfunctional, and the subsequent hemolysis is the predominant finding.

Alpha thalassemia can be diagnosed prenatally. The test is carried out if the pregnancy occurs in a family with a prior history of alpha thalassemia or if the parents belong to an ethnic group with a high disease prevalence. The diagnosis of HbH disease cannot be accurately made before birth; however, neonatal screening allows for the detection of elevated levels of hemoglobin Bart's after birth [12] [13]. 

In the human organism, blood is responsible for carrying oxygenized molecules to the tissues so that they can remain functional and viable. Oxygen is transported to every region of the body via the red blood cells, which contain hemoglobin, a metalloprotein capable of binding with oxygen molecules.

Hemoglobin consists of a heme molecule and four globin chains. There are four types of globin chains, the alpha (α), beta (β), gamma (γ) and delta (δ) chains. Depending on the type of chains a particular hemoglobin is made of, the molecule presents with 3 forms:

• Hemoglobin A. It is the primary counterpart in adult individuals and consists of two alpha and two beta chains.
• Hemoglobin F. It is primarily found in fetal blood and consists of two alpha and two gamma chains. Its concentration is extremely reduced in the adult population.
• Hemoglobin A2, containing two alpha and two delta chains.

Patients affected by alpha thalassemia display a distorted production of alpha chains, which are contained in all three types of hemoglobin molecules. Alpha chains are reduced and beta chains dominate, leading to decreased molecular stability and anemic symptoms.

Alpha thalassemia syndromes exhibit a higher prevalence in individuals born in the Mediterranean region, Asia and the Middle East. A single gene accounts for the disruption of the production of the alpha chains; various mutations or deletions are responsible for the condition. An interesting fact is that the thalassemic, impaired structure of the red blood cells offers some protection against malaria; as a result, populations with a high prevalence of malaria appear to exhibit higher rates of alpha thalassemia. This is viewed as a result of the natural selection process [1] [2] [3] [4]. 

Alpha thalassemia is a disease that affects a compound found in the red blood cells, called haemoglobin. Haemoglobin is the element responsible for carrying oxygen to the organs and tissue in order to keep them functional and living. Patients with alpha thalassemia inherit the disease from their parents and exhibit an abnormal haemoglobin structure, that is unable to carry enough oxygen with the blood. Not every patient with alpha thalassemia is equally affected by the disease, however. The degree of haemoglobin abnormality dictates the severity of the symptoms caused: if a patient has only a small amount of abnormal haemoglobin, they may exhibit no symptoms whatsoever; embryos with no normal haemoglobin, on the other hand, may be stillborn or not even survive until birth. 

Alpha thalassemia is a disease that specifically causes the diminished production of the alpha globin chains, which are a part of the total of the haemoglobin chains. Beta thalassemia is another similar condition, that affects the other chain types, the beta chains. The disease is mostly found in the Mediterranean region, Asia and Africa.   

There are various types of alpha thalassemia, depending on the percentage of the missing alpha chains. Silent carriers only carry a thalassemia gene, but compose adequate functional haemoglobin and, as a result, have no anemic symptoms. Individuals with HbH disease or hydrops fetalis, both alpha-thalassemia subcategories, experience severe medical problems. Fetuses with hydrops fetalis produce no normal haemoglobin and may not survive to birth and patients with HbH require transfusions in order to survive.

Thalassemia can be diagnosed with blood laboratory testing. Prenatal tests are available for parents with a family history of thalassemia or inhabitants of regions where the disease is frequently diagnosed. Neonates may also be screened for alpha thalassemia shortly after birth.

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