Pediatric Thalassemia Clinical Presentation

Updated: Aug 23, 2017
  • Author: Hassan M Yaish, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
  • Print


The history in patients with thalassemia widely varies, depending on the severity of the condition and the age at the time of diagnosis.

  • In most patients with thalassemia traits, no unusual signs or symptoms are encountered.

  • Some patients, especially those with somewhat more severe forms of the disease, manifest some pallor and slight icteric discoloration of the sclerae with splenomegaly, leading to slight enlargement of the abdomen. An affected child's parents or caregivers may report these symptoms. However, some rare types of β thalassemia trait are caused by a unique mutation, resulting in truncated or elongated β chains, which combine abnormally with α chains, producing insoluble dimers or tetramers. The outcome of such insoluble products is a severe hemolytic process that needs to be managed like thalassemia intermedia or, in some cases, thalassemia major.

  • The diagnosis is usually suspected in children with an unexplained hypochromic and microcytic picture, especially those who belong to one of the ethnic groups at risk. For this reason, physicians should always inquire about the patient's ethnic background, family history of hematologic disorders, and dietary history.

  • Thalassemia should be considered in any child with hypochromic microcytic anemia that does not respond to iron supplementation.

  • In more severe forms, such as β thalassemia major, the symptoms vary from extremely debilitating in patients who are not receiving transfusions to mild and almost asymptomatic in those receiving regular transfusion regimens and closely monitored chelation therapy.

  • Children with β thalassemia major usually demonstrate none of the initial symptoms until the later part of the first year of life (when β chains are needed to pair with α chains to form hemoglobin (Hb) A, after γ chains production is turned off). However, in occasional children younger than 3-5 years, the condition may not be recognized because of the delay in cessation of Hb F production.

  • Patients with Hb E/β thalassemia may present with severe symptoms and a clinical course identical to that of patients with β thalassemia major. Alternatively, patients with Hb E/β thalassemia may run a mild course similar to that of patients with thalassemia intermedia or minor. This difference in severity has been described among siblings from the same parents. Some of the variation in severity can be explained based on the different genotypes, such as the type of β thalassemia gene present (ie, β+ or β-0), the co-inheritance of an α thalassemia gene, the high level of Hb F, or the presence of a modifying gene These changes are caused by massive expansion of the bone due to the ineffective erythroid production.

  • The ineffective erythropoiesis also creates a state of hypermetabolism associated with fever and failure to thrive.

  • Occasionally, gout due to hyperuricemia, as well as kidney stones, are seen more frequently as patients with thalassemia major are living longer. Chronic anemia and exposure to chelating agents were thought to be blamed for this complication. [12]

  • Iron overload is one of the major causes of morbidity in all patients with severe forms of thalassemia, regardless of whether they are regularly transfused.

    • In transfused patients, heavy iron turnover from transfused blood is usually the cause; in nontransfused patients, this complication is usually deferred until puberty (if the patient survives to that age).

    • Increased iron absorption is the cause in nontransfused patients, but the reason behind this phenomenon is not clear. Many believe that, despite the iron overload state in these patients and the increased iron deposits in the bone marrow, the requirement for iron to supply the overwhelming production of ineffective erythrocytes is tremendous, causing significant increases in GI absorption of iron.

    • Bleeding tendency, increased susceptibility to infection, and organ dysfunction are all associated with iron overload.

  • Poor growth in patients with thalassemia is due to multiple factors and affects patients with well-controlled disease as well as those with uncontrolled disease.

  • Patients may develop symptoms that suggest diabetes, thyroid disorder, or other endocrinopathy; these are rarely the presenting reports.



Patients with thalassemia minor rarely demonstrate any physical abnormalities. Because the anemia is never severe and, in most instances, the Hb level is not less than 9-10 g/dL, pallor and splenomegaly are rarely observed.

In patients with severe forms of thalassemia, the findings upon physical examination widely vary, depending on how well the disease is controlled. Findings include the following:

  • Children who are not receiving transfusions have a physical appearance so characteristic that an expert examiner can often make a spot diagnosis.

  • In Cooley's original 4 patients, the stigmata of severe untreated β thalassemia major included the following:

    • Severe anemia, with an Hb level of 3-7g/dL

    • Massive hepatosplenomegaly

    • Severe growth retardation

    • Bony deformities

  • These stigmata are typically not observed; instead, patients look healthy. Any complication they develop is usually due to adverse effects of the treatment (transfusion or chelation).

  • Bony abnormalities, such as frontal bossing, prominent facial bones, and dental malocclusion, are usually striking.

  • Severe pallor, slight to moderately severe jaundice, and marked hepatosplenomegaly are almost always present.

Complications of severe anemia are manifested as intolerance to exercise, heart murmur, or even signs of heart failure. Growth retardation is a common finding, even in patients whose disease is well controlled by chelation therapy. Patients with signs of iron overload may also demonstrate signs of endocrinopathy caused by iron deposits. Diabetes and thyroid or adrenal disorders have been described in these patients. In patients with severe anemia who are not receiving transfusion therapy, neuropathy or paralysis may result from compression of the spine or peripheral nerves by large extramedullary hematopoietic masses.



Thalassemias are inherited disorders caused by various gene mutations. The clinical expression and severity are subject to numerous factors that may either mask the condition or exaggerate the symptoms, leading to a more severe disease.