Implications of Population Screening for Thalassemias and Hemoglobinopathies in Rural Areas of West Bengal, India: Report of a 10-Year Study of 287,258 Cases.

Thalassemia and hemoglobinopathies are the most common cause of high morbidity and mortality in India. Detection of carriers and premarital counseling play an important role in preventing the birth of a thalassemic child. The present study aimed to detect large numbers of asymptomatic carriers in rural areas of West Bengal, India. The present cross-sectional study was conducted over a period of 10 years. Thalassemia awareness programs and detection camps were organized at the community level. After signed written consent was obtained, the collected blood samples were subjected to a complete blood count (CBC) in an automated blood cell counter and then analyzed by high performance liquid chromatography (HPLC); in difficult cases, samples were sent to the reference laboratory for molecular characterization. Out of 287,258 samples collected, 32,921 (11.46%) cases revealed abnormal hemoglobins (Hbs); of these, 31,782 (11.06%) carried heterozygous states (carriers/traits), and the remainder were either homozygous or compound heterozygous for different hemoglobinopathies. Two common variants were revealed in the study, namely ß-thalassemia (ß-thal) (7.23%) and Hb E [ß26(B8)Glu→Lys, HBB: c.79G>A] (2.77%) traits. Among homozygous or compound heterozygous states, Hb E/ß-thal (0.14%) and ß-thal major (ß-TM) (0.12%) were predominant. In rural areas of West Bengal, the most common Hb variants detected were ß-thal and Hb E traits. In view of the high prevalence of hemoglobinopathies in this region, routine premarital screening and genetic counseling should be emphasized and encouraged to prevent the birth of a thalassemic child, and thus curtailing the burden on families and the health economy.

[The first case of acquired hemoglobinopathy H in Russia in a patient developing unclassified myelodysplastic syndrome/myeloproliferative disease].

A 55 year-old man with hemolytic anemia is described. Careful clinical and laboratory studies showed that this condition was a manifestation of non-hereditary hemoglobinopathy N. The clinical symptoms suggested acquired hemoglobinopathy N that devloped parallel to myelodysplastic syndrome/myeloproliferative disease.

Acquired haemoglobin H disease associated with myelodysplastic syndrome.

A 60-year-old male patient presented with jaundice. Initial investigations showed anemia, indirect hyperbilirubinemia, raised Lactic Dehydrogenase (LDH) and increased reticulocyte count suggestive of hemolysis. Considering hemolysis low MCV and basophilic stippling on peripheral film, hemoglobin electrophoresis was done that showed Haemoglobin H (15.5%) that in the absence of family history was thought to be acquired. After bone marrow examination, the final diagnosis was Myelodysplastic Syndrome (MDS), Refractory anemia with excess of blast (RAEB) associated with acquired Haemoglobin H (Hb H) disease.

Prevalence of erythrocyte haemoglobin H inclusions in unselected patients with clonal myeloid disorders.

Patients with clonal myeloid disorders, especially myelodysplastic syndromes (MDS), may acquire alpha-thalassaemia. To estimate the prevalence of this erythrocyte phenotype, we examined brilliant cresyl blue-stained blood smears from 201 patients with neoplastic myeloid disorders and 282 controls (195 non-clonal anaemia, 62 with medical illnesses without anaemia and 25 healthy persons). Haemoglobin H inclusions were detected in 8/100 patients with MDS (8%) and 2/81 (2.5%) patients with myeloproliferative disorders, but in none of the acute leukaemia patients or controls. We conclude that the emergence of thalassaemic clones may be relatively common in the disordered marrow milieu of MDS.

[Acquired alpha-thalassemia as early sign for myelodysplastic syndrome (refractory anaemia) with secondary haemochromatosis]. / Alpha-thalassémie acquise révélatrice d'un syndrome myélodysplasique de type anémie réfractaire avec hémochromatose secondaire.

We report the case of a 59 year old man presenting a regenerative microcytic hypochromic anaemia. The investigations revealed the presence of haemoglobin H, suggesting abnormalities in the alpha-globin chains synthesis. Alpha-thalassemia was thus suspected. The patient had no personal or familial history. The association with aniso-poïkilocytosis and a marked iron overload (ferritinemia > 1,500 microg/L) suggested a myelodysplastic syndrome, which was confirmed with a bone marrow aspiration. The pattern was consistent with the Acquired alpha-Thalassemia-Myelodysplastic Syndrome (ATMDS). About a hundred cases are listed worldwidely and collected in an international registry. The causes of ATMDS are ignored, but recent reports indicate that the ATRX gene may be implicated in the pathogenesis. ATRX is a chromatin-associated protein, involved in the transcription of several genes. The alpha globin genes could be one of the targets of the ATRX protein.

[Acquired hemoglobin H disease associated with a myelodysplastic syndrome]. / Enfermedad de la hemoglobina H adquirida asociada a síndrome mielodisplásico.

Some patients found to have clonal panmyelopathies develop an acquired defect of haemoglobin synthesis clinically similar to haemoglobin H disease. A 58 year-old male diagnosed of simple refractory anaemia developed microcytosis and hypochromia. At the same time, his myelodysplastic syndrome became a refractory anaemia with excess of blasts. 33% of the red blood cells had "golf ball" inclusions after incubation with brilliant cresyl blue. Cellulose acetate electrophoresis revealed an haemoglobin H band. The globin chain synthesis alpha/beta ratio was 0.69. The molecular analysis demonstrated the integrity of both alpha genes in each chromosome. There were no familiar antecedent of haemoglobinopathy.