The Clinical and Laboratory Spectrum of Hb C [β6(A3)Glu→Lys, GAG>AAG] Disease

Abstract

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/β⁰-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 ^Gγ 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.

• Hb C disease
• Hb CC
• Hb C/β-thalassemia (β-thal)
• Hemoglobinopathies

ACKNOWLEDGMENTS

The authors thank David H.K. Chui, Ph.D. (Director, Hemoglobin Diagnostic Reference Laboratory, Boston University, Boston, MA, USA) for performing Hb DNA analysis and Terri Davis (St. Jude Children’s Research Hospital, Memphis, TN, USA) for assistance with text formatting.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.