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The proband was a male in his seventies who came to our facility because of shortness of breath. He was not anemic but presented dissociation between oxygen saturation (SpO 2 ) and partial pressure of oxygen (PaO 2 ) by blood gas analysis, and also demonstrated hemoglobinopathy after measurement of Hb A 1c using high performance liquid chromatography (HPLC). Twenty-three percent of unknown hemoglobin (Hb) bands were detected. After sequencing the β-globin gene, we noted a missense mutation at codon 74 ( G GC> C GC) (Gly→Arg) of the β-globin chain and he was diagnosed with Hb Aalborg ( HBB : c.223G>C). One of the proband's siblings was diagnosed to have a low SpO 2 level and also diagnosed to carry Hb Aalborg; she was also mildly anemic. This is the first known familial case of Hb Aalborg in Japan. In addition to Hb Aalborg, our case had underlying chronic obstructive pulmonary disease (COPD). Herein we present this case as a rare addition to the hematological literature.

Patients with unstable hemoglobin (Hb), caused by a qualitative abnormality in α- and β-globin genes, are often asymptomatic or mildly symptomatic. It is often difficult to diagnose unstable Hb patients with only mild hemolysis or low oxygen saturation. We herein report a case of a family with an unstable Hb, specifically, Hb Sydney ( HBB : c.203T>C), an abnormal β-globin chain. A 5-year-old boy was referred to our hospital for low percutaneous oxygen saturation (SpO 2 ) in the setting of bronchitis. During hospitalization, low SpO 2 persisted despite the improvement in respiratory distress symptoms. As he had mild hemolysis and splenomegaly, his disease was diagnosed to carry Hb Sydney based on gene analysis. His mother and brother also carried Hb Sydney. In this case, bronchial asthma had been treated, but unstable Hb was not assessed. Low SpO 2 may be tolerated and overlooked in cases of asthma and it took time to diagnose this patient. The present case suggests that unstable Hb should be considered in patients with bronchial asthma and prolonged low SpO 2 .

A 65-year-old Japanese man presented with acute myocardial infarction (AMI) and polycythemia. Biochemical studies of the patient's hemoglobin (Hb) and the sequencing of his globin genes revealed that the polycythemia was secondary to a high oxygen affinity Hb variant, Hb Fuchu-II. Hb variants with high oxygen affinity can be an additional thrombotic risk factor in older patients and/or those with other risk factors. The patient was diagnosed with hemoglobinopathy after the development of AMI and exemplifies the importance of recognizing such conditions and of taking appropriate prophylactic interventions.

We undertook a 25-year observation of a female patient with an unstable variant, Hb Nottingham or β98(FG5)Val→Gly, GTG>GGG. The proband was diagnosed with Hb Nottingham at the age of 9 years. Splenectomy was performed in order to successfully aid her height growth due to chronic anemia at the age of 11, although anemia improvement was transient. She experienced pregnancy/delivery twice, at age 23 and 26, respectively. During both pregnancies, a large number of nucleated red blood cells (NRBCs) appeared in her peripheral blood. No developmental delay of the fetus was noted in either pregnancy, and she gave birth without any maternal complications or perinatal problems. Both babies were diagnosed with Hb Nottingham. To the best of our knowledge, this is the first report of a long-term observation of a proband with Hb Nottingham, including her pregnancy/delivery and the neonatal course of her children with the same disorder.

Hemoglobin Hammersmith, a rare, unstable hemoglobin variant, was diagnosed in a 9-year-old Japanese girl. She presented with the typical manifestations of this disorder, including neonatal hyperbilirubinemia, followed by progressive hepatosplenomegaly, jaundice, and bilirubinuria. Because of severe hemolytic anemia, she received transfusions of red blood cells every 3 to 4 weeks. However, she underwent splenectomy at the age of 4 years and has continued to be in partial remission without requiring further transfusions. DNA sequence analysis of the polymerase chain reaction-amplified beta-globin gene revealed a point mutation (T --> C) in the second nucleotide of the 42nd codon of the beta-globin chain (beta 42(CD1) Phe --> Ser)., ((c) 2005 Wiley-Liss, Inc.)

We encountered two patients with abnormally low glycohemoglobin levels in spite of normal plasma glucose levels. Since the presence of an abnormal hemoglobin was suggested by high-performance liquid chromatography (HPLC), gene analysis of these two patients was conducted by single-strand conformation polymorphism (SSCP) analysis followed by direct sequencing, and Hb Kamakura with one base substitution (beta3 Leu --> Val) in the beta globin gene was detected in both patients. There was been only one report of Hb Kamakura in Kanagawa Prefecture, and our patients represent the second and third cases, respectively.

An abnormal hemoglobin (Hb) found in a 63-year-old Japanese woman presenting with asymptomatic chronic microcytic anemia was extensively characterized by the conventional protein chemistry, restriction mapping of the genomic DNA with Bgl II digestion, and direct sequencing of a relevant segment of the mutant non-alpha-globin gene. The results identified a hybrid globin with delta- and beta-like sequences, from position 1 to 87 and from 105 to 146 (C-terminal), respectively. The delta beta fusion gene was produced by deletion of 7.4 kb involving parts of the two closely linked genes. The break point was somewhere within the homologous 58 bps, from codon 88 to IVS-II-7. The same deletion had repeatedly been reported in Hb Lepore Washington-Boston. The expression of a mild (delta beta)(+)-thalassemia trait in the present case completely agreed with previous reports on representative Hb Lepore heterozygotes. The basis for the activity of Hb Lepore gene which is several times higher than the delta-globin gene was discussed.

Hereditary HbH disease was found in a Japanese family. The propositus showed hypochromic microcytic anemia and chronic hemolysis. HbH inclusion bodies were detected in red cells, and an abnormal band corresponding HbH was found in an isoelectric focusing of the hemolysate. Gene analysis of the propositus revealed double heterozygosity for alpha + and alpha zero thalassemias. Four of six his siblings shared the alpha zero thalassemia and one the alpha + thalassemia. Another one was normal. The alpha + thalassemia was of 3.7 kb-deletion type and alpha zero was close to Southeast Asian type. This is the fourth Japanese family with hereditary HbH disease.