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Hemoglobin (Hb) H/Constant Spring disease is a common nondeletional Hb H disease, typically causing a more severe phenotype than the deletional Hb H disease counterpart. Hb Tak, resulting from a dinucleotide insertion (+AC) at codon 146 of beta-globin gene, has an increased oxygen affinity and usually presents with polycythemia. We studied a case of a 4-year-old Thai boy with a severe, early-onset anemia. To our knowledge, he is the first reported patient with Hb H/Constant Spring disease and heterozygous Hb Tak. Trio-whole-exome sequencing does not identify other genetic variants that may contribute to the severity of anemia. The observation suggests that coinherited Hb H/Constant Spring and heterozygous Hb Tak lead to severe hemolytic anemia., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Screening for iron deficiency anemia (IDA) in infants is usually carried out by hemoglobin (Hb) level and mean corpuscular volume (MCV). A coinherited thalassemia carrier may confound the diagnosis of IDA. This study aimed to characterize the hematologic parameters in infants with IDA and in thalassemia carriers, and to study the use of red cell parameters in IDA screening in a thalassemia-endemic area. Healthy infants, 6 to 12 months of age were enrolled. Blood samples were taken for complete blood count, ferritin level, Hb analysis, and polymerase chain reaction for alpha-thalassemia. IDA was defined as Hb <11.0 g/dL and ferritin <12 μg/L. Formulae calculated from red cell parameters to distinguish thalassemia carriers were analyzed. Eighty-five infants, 8.3±2.4 months of age, including 48 (56.5%) male infants were enrolled. Sixteen infants (18.8%) had IDA. There were 25 thalassemia carriers (29.4%), 1 Hb H disease, and 1 homozygous Hb E. Hb levels and MCV in the IDA and thalassemia carrier groups were significantly lower than those in the normal group. Area under the curve of Mentzer index (MCV/red blood cell count <13) to suggest thalassemia carriers was 0.867 (95% confidence interval: 0.784-0.951), and the sensitivity and specificity were 92.6% and 72.4%, respectively. In conclusion, both Hb level and Mentzer index are recommended for screening of IDA and thalassemia carriers in the population.

Among 990 young male adolescents studied, only 7 were anemic. Three of the anemics had beta-thalassemia trait and 4 had probable alpha-thalassemia trait. Forty-six individuals with hemoglobinopathies were detected: 29 with probable alpha-thalassemia trait, 10 with beta-thalassemia trait and 7 with heterozygous HbE. Heterozygous alpha and beta-thalassemia occurred predominantly in Chinese while heterozygous HbE was found entirely in Malays. There were no cases of established iron deficiency anemia and only 1 had iron deficient erythropoiesis. Folate deficiency occurred only in 8 subjects with thalassemia traits, and no vitamin B12 deficiency was detected.

The clinical spectrum of HbH disease varies from a benign disorder to a severe anemia which is blood-transfusion dependent. Heterogeneity at the clinical level is now being understood in terms of the underlying molecular defects. In this study a mild phenotype found in a group of patients with HbH disease is associated with two types of alpha-thalassemia. These are: alpha+-thalassemia (-alpha 3.7/) and alpha 0-thalassemia (--SEA/). In contrast, a second group with more severe HbH disease has a non-deletional alpha-thalassemia defect instead of alpha+-thalassemia (genotype alpha alpha T/--SEA). In the majority of cases, the basis for non-deletional alpha-thalassemia is Hb Constant Spring.