[Testicular Tumor in a Patient with Delta Thalassemia Complicated with Hereditary Persistence of Fetal Hemoglobin].

A 30s male was diagnosed as having the left testicular tumor in 2010. He received the anti-neoplastic chemotherapy, and could achieve the complete remission. But, he relapsed with solitary retroperitoneal lymph node swelling in 2012, and he was referred to our hospital. Laboratory examination on his admission showed the significant increase of fetal hemoglobin (HbF) up to 16.4%. But, neither anemia nor hemolysis was found at that time. Coexistence of therapy-related myeloid neoplasm or HbF production by metastatic lesion was not definite. Isoelectrofocusing of his hemolysate showed the faint HbA2 in addition to dense HbF band. Molecular analysis of his Hb gene revealed the homozygous (G)gamma-158 (C-T) together with homozygous delta-77(T-C). From these findings, he was diagnosed as having hereditary persistence of HbF (HPFH) and homozygous delta thalassemia. The precise incidence of such combined genetic variation has been unknown because the majority of such cases seem to show no significant clinical symptoms as our case. Whereas, it seems necessary to remind the possibility of such genetic variation when adult patients with various acquired diseases such as testicular tumor or hematologic malignancies show the elevated HbF level.

εGγAγδß0-thalassemia: a rare but clinically significant cause of hemolytic anemia in infants.

Normal hemoglobin is made of a tetramer of 2 α-globin and 2 ß-globin polypeptide chains. Deletions in the ß-globin gene cluster can range from a few hundred base pairs to loss of the entire cluster resulting in rare, but clinically significant, thalassemias. One such entity is εGγAγδß0-thalassemia, a condition that presents within the first few weeks of life as a Coombs-negative hemolytic anemia and is not identified on routine newborn screening or hemoglobin electrophoresis.

Erythrocytosis in a child due to Hb Andrew-Minneapolis [ß144(HC1)Lys→Asn (AAG>AAT or AAC)] associated with a Spanish (δß)(0)-thalassemia.

We report a rare association of δß-thalassemia (δß-thal) and a hemoglobin (Hb) variant with high oxygen affinity in a Spanish newborn. The proband had no Hb A and showed microcytosis and hypochromia; the peripheral blood smear was compatible with a thalassemia trait. Molecular studies revealed that the proband had a Spanish (δß)(0)-thal (inherited from his father) and also carried a de novo variant (Hb Andrew-Minneapolis) because from the point of hematology, his mother was quite normal. The hemoglobinopathies with high affinity for oxygen constitute an infrequent cause of secondary congenital erythrocytosis. The degree of erythrocytosis and the resulting clinical manifestations are highly variable, depending on the degree of altered oxygen affinity and the presence of thalassemic genes. Thus, when these variants are associated with ß(0)- or δß-thal, as in our case, the proportion of abnormal Hb is ∼100.0%, which may cause polycythemia, hyperviscosity, and iron deficiency. This type of association is very rare and few have been described, especially in children, as they would normally be detected in adults as the increased packed cell volume (PCV) also increases blood viscosity and causes the typical symptoms (cephalalgia, drowsiness, dizziness). The association of a high oxygen affinity Hb and a δß-thal presents a greater degree of erythrocytosis than when this same variant is associated with a ß(0)-thal, mainly because the Hb F percentage is usually greater in the δß-thal, and Hb F normally shows a greater affinity for oxygen and a reduced P(50), although one must always take into account the degree of oxygen affinity of the Hb variant. Familial erythrocytosis and an abnormal electrophoresis finding are indicative of a high affinity Hb. However, the absence of these findings does not reject the possibility of hemoglobinopathies, and in these cases, functional and molecular studies would be justified and should be mandatory for the differential diagnosis of erythrocytosis.

Thalassemia-like phenotype in a novel complex hemoglobinopathy with α, ß, δ globin chain abnormalities.

The occurrence of multiple abnormalities of α, ß, δ, and γ globin genes may lead to unusual and complex phenotypes when they arise simultaneously in the same individual. Here, we report the findings of an African American boy who coinherited 3 heterozygous globin gene abnormalities: the unstable ß-globin chain variant; hemoglobin (Hb) Showa-Yakushiji [ß110(G12) Leu→Pro], the δ-globin chain variant; HbB2 [δ16(A13) Gly→Arg] and α-thalassemia (α-thal); (α-/αα). Hb Showa-Yakushiji had been previously described in Japanese, Indian, and European populations. We report its first occurrence in a child of African ancestry who presented with anemia not responsive to iron and an incomplete ß-thalassemia minor phenotype. Although the clinical and laboratory features of Hb Showa-Yakushiji mimic those of a ß-thalassemia, the coinheritance of the δ-globin chain variant Hb B2 suppressed the relative increase in Hb A2 usually observed in heterozygotes for the Hb Showa-Yakushiji mutation. Protein-based methods detected only a trace amount of HbB2 and failed to reveal presence of Hb Showa-Yakushiji and α-thal. The latter were only identified through DNA analyses. The diagnostic difficulties, molecular characteristics, and genotype/phenotype correlations of this novel complex hemoglobinopathy syndrome are reviewed.

Co-inheritance of ß- and δ-thalassemia compromising prenatal screening in a Chinese couple seeking prevention.

Although δ-globin gene mutations have no clinical implications, association of ß- and δ-thalassemia may lead to misdiagnosis. We describe the case of a Chinese woman who was assumed to have an α-thalassemia heterozygote, but was later shown to have ß-thalassemia with a normal amount of HbA(2) caused by the -77 mutation of the δ-globin gene. This study highlights the importance of considering δ-thalassemia during ß-thalassemia screening to avoid false-negative results in the detection of at-risk couples.

Oral phosphodiesterase type 5 inhibitors alleviate recurrent priapism complicating thalassemia intermedia: a case report.

INTRODUCTION: Recurrent ischemic priapism still remains a serious and difficult to treat complication of certain hematological disorders. Elucidation of the underlying pathophysiologic mechanisms and application of new effective prophylactic treatments are needed. AIM: To present the efficacy of phosphodiesterase type 5 inhibitors (PDE5is) as a preventive measure against ischemic priapism recurrences complicating thalassemia intermedia. METHODS: We report on the case of a 19-year-old Caucasian man with thalassemia intermedia complicated by recurrent episodes of priapism following therapeutic splenectomy. After failure of conventional measures to control recurrences, a trial of long-term PDE5is use was initiated. MAIN OUTCOME MEASURES: PDE5is efficacy based on clinical patient history. RESULTS: Within 2 months of PDE5i preventive strategy, priapism recurrences nearly resolved. At 6 months, prophylaxis was discontinued. At 12 months, the patient reported clear improvement and satisfaction, experiencing rare episodes of priapism and a physiologic erectile function. CONCLUSIONS: PDE5 dysregulation seems to be an underline pathogenetic mechanism of thalassemia intermedia-associated priapism. It appears that PDE5is might have a role in the clinical management of such patients and their preventive efficacy warrants further testing in clinical trials.