863 was mildly icteric with frontal bossing, and had an enlarged spleen palpable 11 cm below the costal margin. The hemo- globin level was 4.7 gm/dl, and a hemo- globin electrophoresis revealed HbE 52% and HbF 48%, consistent with HbE/β 0 -thalassemia. The hypersplenism was accompanied by moderate thrombo- cytopenia and leukocytosis. The patient’s father and mother had no symptoms and were normal on physical examination. However, three siblings of the father had died with anemia and splenomegaly. Hematologic parameters and molecular analyses of the α- and β- globin gene loci were obtained on the proband and his family (Table). For mol- ecular analyses of the α- and β-globin gene loci, DNA was extracted from pe- ripheral blood leukocytes and the β-glo- bin gene region was amplified by poly- merase chain reaction. The β E mutation (codon 26 GAG→AAG) was identified by dot blotting with allele-specific nonra- dioactive oligonucleotide probes and by direct nucleotide sequencing. The β 0 -thalassemia nonsense mutation (codon 17 AAG→TAG) was detected by direct nucleotide sequencing of the PCR prod- uct. The ζ- and α-globin genotypes were determined by Southern blotting with α- and ζ-globin gene-specific radioactive probes. 5 The patient’s father was found to have HbE/β 0 -thalassemia. In addition, unlike The thalassemia syndromes are the most common single-gene disorders in the world 1 and are highly prevalent in Thai- land, Laos, Cambodia, the Indian sub- continent, southern China, southern Europe, and Africa. The interaction of hemoglobin E, α-thalassemia, and β 0 -thalassemia can result in clinical man- ifestations ranging from severe anemia to asymptomatic phenotypes. 2,3 More than 1 million persons of Southeast Asian ori- gin have resettled in the United States 4 and now account for a majority of indi- viduals with thalassemic mutations in this country. We describe a new kindred in which the proband is a child with HbE/β 0 -tha- lassemia and severe anemia, whereas his C Coinheritance of α-thalassemia-1 and hemoglobin E/β 0 -thalassemia: Practical implications for neonatal screening and genetic counseling Lakshmanan Krishnamurti, MD, David H. K. Chui, MD, Michele Dallaire, MS, Bonnie LeRoy, MS, John S. Waye, PhD, and John P. Perentesis, MD father, who carries an α-thalassemia-1 mutation in addition to HbE/β 0 -tha- lassemia, has only a mild anemia. This re- port highlights the complex interactions of HbE, α-thalassemia, and β 0 -tha- lassemia in Southeast Asian populations, pitfalls in neonatal screening, and the im- portant role of molecular testing in se- lected kindreds. CASE REPORT The proband, a 31-month-old child of Laotian descent, was identified on neonatal screening as having HbE and hemoglobin F (FE); it was assumed that he had homozygous HbE. At the age of 9 months, he had failure to thrive and a he- moglobin level of 7.4 gm/dl. He remained anemic despite a 5-month trial of an oral iron supplement. On subsequent referral to the Univer- sity of Minnesota Hospital at 14 months of age, the patient was found to be se- verely growth retarded, with height 77 cm and weight 8.14 kg, both far below the 5th percentile (Figure). He was pale, From the Department of Pediatrics and the Institute of Human Genetics, University of Minnesota Medical School, Minneapolis, and the Provincial Hemoglobinopathy DNA Diagnostic Laboratory and Department of Pathology, McMaster University, Hamilton, Ontario, Canada Submitted for publication Dec. 29, 1996; revision received Sept. 24, 1997; accepted Oct. 15, 1997. Reprint requests: John P. Perentesis, MD, Pedi- atric High-Risk Hematology/Oncology Program, University of Minnesota Cancer Center, Room 554, 425 East River Rd., Minneapolis, MN 55455. Copyright © 1998 by Mosby, Inc. 0022-3476/98/$5.00 + 0 9/22/87192 HbE Hemoglobin E HbF Hemoglobin F PCR Polymerase chain reaction Hemoglobin E (HbE), α-thalassemia, and β-thalassemia are common among Southeast Asians and often occur in compound heterozygous states that compli- cate neonatal screening. We describe a kindred with α-thalassemia-1, HbE, and β 0 -thalassemia. The proband had HbE/β 0 -thalassemia, with severe anemia and failure to thrive. His father also had HbE/β 0 -thalassemia but had coinherited α- thalassemia-1 and was free of symptoms. (J Pediatr 1998;132:863-5) See editorial, p. 765.