Abnormal
globin chain biosynthesis may result in deficient quantity (
thalassemia) or structural variation (
abnormal hemoglobins) and traditionally, they represent two phenotypically distinct groups of disorders. However, the phenotypic expression of unstable
hemoglobin variants often combine features of
thalassemia together with variable peripheral
hemolysis. To achieve definitive diagnosis in a child presenting with
hemolytic anemia along with features associated with
thalassemia intermedia, we evaluated clinical, hematological, biochemical,
globin biosynthetic and molecular data. Definitive diagnosis was achieved by
DNA analysis which characterized the proband to be a compound heterozygote for a common alpha-thalassemia-2 deletion (3.7 kb) and
Hb Questembert (alpha131[H14]
Ser>Pro) caused by a C>T mutation in
codon 131 of the alpha1
globin gene in trans. The phenotype of
thalassemia intermedia with marked dyserythropoiesis, found in patients inheriting
alpha-thalassemia mutations along with unstable
alpha-globin variants (i.e., alpha-thalassemic
hemoglobinopathies), represents a distinct type of thalassemic syndrome. The proband in this study additionally had variable peripheral
hemolysis, presumably related to characteristics of the unstable
Hb Questembert. There is minimal experience for the management of such atypical cases and this case illustrates that it is probably insufficient to monitor clinical status in patients with such
hemoglobinopathies based only on the levels of
hemoglobin.