title: 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/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.
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-3678, USA.
authors.forename: Cathleen M
authors.initials: CM
authors.lastname: Cook
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Smeltzer
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Mortier
authors.forename: Susan E
authors.initials: SE
authors.lastname: Kirk
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Despotovic
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
authors.forename: Jane S
authors.initials: JS
authors.lastname: Hankins
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D006444:Hemoglobin C / Q000235:genetics*; D006453:Hemoglobinopathies / Q000235:genetics* / Q000473:pathology*; D006455:Hemoglobins, Abnormal / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D017354:Point Mutation; D055815:Young Adult; D017086:beta-Thalassemia / Q000235:genetics / Q000473:pathology
chemical_list: D006455:Hemoglobins, Abnormal; C119901:hemoglobin Osu-Christiansborg; D006444:Hemoglobin C; C038623:hemoglobin Hope; C037659:hemoglobin Lepore