The clinical and laboratory spectrum of Hb C [β6(A3)Glu→Lys, GAG>AAG] disease

Hemoglobin. 2013;37(1):16-25. doi: 10.3109/03630269.2012.753547.


Newborn screening (NBS) provides early diagnosis of sickle hemoglobinopathies. After Hb S [β6(A3)Glu→Val, GAG>GTG], Hb C [β6(A3)Glu→Lys, GAG>AAG] is the most common hemoglobin (Hb) abnormality identified in the United States (1,2). Published data regarding children with Hb C disease are limited. This study was conducted to summarize a single institution's clinical and laboratory data for patients with Hb C disease, specifically homozygous Hb CC and its variants over a 10-year period. Forty-seven patients, whose mean age at diagnosis was 2.9 years (range 0.04 to 23 years), were identified. Twenty-nine had Hb CC and the remainder had compound heterozygous variants [10 Hb C/β(+)-thalassemia (β(+)-thal), four Hb C/β(0)-thal, and one each with Hb C/Hb Hope or β136(H14)Gly→Asp (GGT>GAT), Hb C/Hb Lepore (a hybrid δβ-globin gene), Hb C/HPFH (hereditary persistence of fetal Hb) [probably a (G)γ HPFH-2 (the Ghanaian type)], and Hb C/Osu-Christiansborg or β52(D3)Asp→Asn (GAT>AAT)]. All patients had mild microcytic anemia with reticulocytosis and frequent target cells on peripheral smear. Splenomegaly or cholelithiasis occurred in 2.6% of patients <8 years of age, however, these symptoms were more common (71.0%) in patients >8 years of age. No patient had serious infections or painful events resembling vasoocclusion. Accurate diagnosis and understanding of Hb C-related disorders helped to avoid confusion with sickle hemoglobinopathies and aided in proper clinical management.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Erythrocyte Indices
  • Erythrocytes / metabolism
  • Erythrocytes / pathology
  • Female
  • Hemoglobin C / genetics*
  • Hemoglobinopathies / genetics*
  • Hemoglobinopathies / pathology*
  • Hemoglobins, Abnormal / genetics
  • Heterozygote
  • Homozygote
  • Humans
  • Infant
  • Male
  • Point Mutation
  • Young Adult
  • beta-Thalassemia / genetics
  • beta-Thalassemia / pathology


  • Hemoglobins, Abnormal
  • hemoglobin Osu-Christiansborg
  • Hemoglobin C
  • hemoglobin Hope
  • hemoglobin Lepore