Pediatric Thalassemia Differential Diagnoses

Updated: Aug 19, 2022
  • Author: Hassan M Yaish, MD; Chief Editor: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK)  more...
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Diagnostic Considerations

The differential diagnoses will depend on the presentation, and patients fall into three clinical categories.

Asymptomatic patients in childhood or later, with mild microcytic hypochromic anemia

Alpha- and beta-thalassemia trait need to be differentiated from iron-deficiency anemia, which is the most common cause of microcytic hypochromic anemia in children. Assessment of the patient's nutritional and family history must be included in this differentiation. A review of the complete blood count (CBC) can be diagnostic, owing to the fact that in thalassemia trait the anemia is mild (usually Hb >9-10 g/dL), with the RBC count elevated and the mean corpuscular volume (MCV) significantly decreased. This discordance is reflected in the Mentzer index, where MCV/RBC is less than 13 in patients with thalassemia trait.

In iron-deficiency anemia, Hb electrophoresis results can be misleading, since the production of HbA2 is suppressed; if there is a strong clinical suspicion, the test should be repeated after the iron-deficiency anemia has been treated. Confirmation of alpha-thalassemia trait can be hard, since Hb electrophoresis is normal, but commercially available polymerase chain reaction (PCR) screening for α-globin 3.7 kb and 4.2 kb deletions has made it easier to screen for patients who are α+ thalassemia carriers, with these individuals commonly being of African or Middle Eastern origin. [2]

Patients with severe hemolytic anemia presenting a few months after birth, or in early childhood.

The concern in this category would be severe beta thalassemia (major or intermedia) or alpha thalassemia (HbH disease). For patients who are transfusion dependent, congenital dyserythropoietic anemia and Diamond-Blackfan anemia should be in the differential. For patients who are not transfusion dependent, Gaucher disease and other storage disorders, as well as malignant osteopetrosis, should be considered. In almost all cases, review of the red cell indices, peripheral blood smear, and Hb electrophoresis, of the child and parents, is usually adequate to reveal the diagnosis. Rarely does any other testing need to be done.

HbH disease can be diagnosed based on inclusions in the RBCs (Heinz bodies), provided a supravital stain is performed, but on Hb electrophoresis, the HbH band tends to be unstable and can be missed. Patients with HbH disease have more than 20% Hb Bart at birth, which allows diagnosis in a newborn screening program. [20]

Patients stillborn with hydrops fetalis

Homozygous α0 thalassemia is not compatible with life (unless intrauterine blood transfusion is administered, which is a rare situation), and a stillbirth with Hb Bart hydrops fetalis usually occurs. Other causes of immune and nonimmune hydrops fetalis should be differentiated from alpha-thalassemia major, a condition that is commonly encountered in Southeast Asia and southern China but is rarely seen outside those regions. [15]

Differential Diagnoses