Pediatric Thalassemia Clinical Presentation

Updated: Dec 16, 2019
  • Author: Hassan M Yaish, MD; Chief Editor: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP  more...
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Presentation

History

Patient history in thalassemia varies widely, depending on the type of thalassemia and the severity of the underlying defect.

In most patients with thalassemia trait, no unusual signs or symptoms are encountered. The diagnosis is usually suspected in children or adults with an unexplained mild microcytic hypochromic anemia, especially those who belong to one of the ethnic groups at risk or are being treated for possible iron deficiency anemia with no response. [2]

Patients with beta-thalassemia major remain asymptomatic until 3-6 months of age or more, when HbF production falls and adequate HbA cannot be produced. (In some patients with persistent HbF production or a β+ mutation, the diagnosis may be delayed until after the first year of life, and patients may not need regular transfusions [thalassemia intermedia].) The symptoms are a progressive, severe microcytic hypochromic anemia (see image below), with abdominal enlargement due to hepatosplenomegaly and occasionally slight icterus. If left untreated, bony and facial changes may manifest, as well as stunted growth. Patients with HbE/β-thalassemia behave similarly to severe beta thalassemia. [11]

Patients with severe alpha thalassemia (HbH disease) may be diagnosed only when they develop aplastic crisis with severe pallor, or hyperhemolysis with jaundice, due to intercurrent infection. Patients with coinheritance of a nondeletional mutation such as Hb Constant Spring (- -/ αCSα) or Hb Quong Sze (- -/ αQZα) have more severe hemolysis and are usually diagnosed in the first year of life, whereas those with 3-gene deletions (- -/- α) have milder disease and may be diagnosed later. The most severe form alpha thalassemia, with 4-gene deletion (- -/- -), presents as stillbirth with hydrops fetalis (Hb Bart hydrops fetalis). [6]  

Peripheral blood film in Cooley anemia. Peripheral blood film in Cooley anemia.
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Physical examination

Physical findings in thalassemia vary widely, depending on the type of thalassemia and the severity of the underlying genetic abnormality. Patients with thalassemia trait will have no abnormal physical findings.

In severe forms of beta thalassemia, since the excess α-globin chains are insoluble, they precipitate in red blood cell (RBC) precursors, destroying them and causing ineffective erythropoiesis. This leads to the following physical findings, usually if the patient is inadequately transfused:

  • Severe pallor, scleral icterus
  • Enlarged abdomen due to hepatosplenomegaly
  • Severe bony changes due to ineffective erythroid production (eg, frontal bossing, prominent facial bones, dental malocclusion)
  • Neuropathy/paralysis due to extramedullary hematopiesis
  • Growth retardation and short stature

In alpha thalassemia, the excess globin chains are γ-globin chains and, later, β-globin chains, which form soluble molecules such as Hb Bart (γ4) and HbH (β4); thus, red cell production is not as badly affected. The anemia seen is often less severe and not associated with ineffective erythropoiesis. Even patients with severe alpha thalassemia (having lost 3 out of 4 genes), with HbH disease, will have findings of mild to moderate hemolytic anemia, as follows:  

  • Pallor, scleral icterus
  • Splenomegaly (hepatomegaly is less common)
  • Absence of bony deformities

Loss of all four α-globin genes leads to hydrops fetalis and is incompatible with life, with the affected fetus being stillborn (Hb Bart hydrops fetalis).

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