Molecular characterization of hemoglobin D Punjab traits and clinical-hematological profile of the patients

Abstract

CONTEXT AND OBJECTIVE: Hemoglobin (Hb) D hemoglobinopathies are widespread diseases in northwestern India and usually present with mild hemolytic anemia and mild to moderate splenomegaly. The heterozygous form of Hb D is clinically silent, but coinheritance of Hb D with Hb S or beta-thalassemia produces clinically significant conditions like thalassemia intermedia of moderate severity. Under heterozygous conditions with coinheritance of alpha and beta-thalassemia, patients show a degree of clinical variability. Thus, our aim was to molecularly characterize the Hb D trait among individuals who were clinically symptomatic because of co-inheritance of alpha deletions or any beta-globin gene mutations. DESIGN AND SETTING: This was a cross-sectional study conducted in an autonomous tertiary-care hospital. METHODS:Complete blood count and red cell indices were measured using an automated cell analyzer. Quantitative assessment of hemoglobin Hb F, Hb A, Hb A2 and Hb D was performed by means of high performance liquid chromatography (HPLC). DNA extraction was done using the phenol-chloroform method. Molecular analyses on common alpha deletions and common beta mutations were done using the Gap polymerase chain reaction and Amplification Refractory Mutation System, respectively. RESULTS: We evaluated 30 patients and found clinical variation in the behavior of Hb D traits. In six patients, the Hb D traits were clinically symptomatic and behaved like those of thalassemia intermedia. Molecular characterization showed that three out of these six were IVS-1-5 positive. CONCLUSIONS: HPLC may not be the gold standard for diagnosing symptomatic Hb D Punjab traits. Hence, standard confirmation should include molecular studies. RESUMO

Profile of Hemoglobin D Trait in West Bengal, India

“…In a small study, six out of the 30 patients of Hb D trait were clinically symptomatic and presented with anaemia, jaundice, pallor, weaknesses and the disease behaviour was like cases of thalassemia intermedia. 7 MCV >80 fl was seen in 81.36%, MCH >28 pg was in 5.60% and normal RDW-CV was seen in all cases of Hb D trait. However, in a study of 11 patients of Hb D trait showed normal clinical and blood count parameters.…”

Hemoglobinopathies and Thalassemias

“…Heterozygous Hb D disease is a benign condition with no apparent illness, but when Hb D is associated with Hb S or β-thalassemia, clinical conditions such as sickling disease and moderate hemolytic anemia may be observed. Heterozygous Hb D is rare and usually presents with mild hemolytic anemia and mild to moderate splenomegaly [9].…”

An Intriguing High Performance Liquid Chromatogram of a Double Heterozygosity for Hb Q-India/Hb D-Punjab

“…Hb D was first described by Itano in 1951 (9). It is the fourth most common Hb variant worldwide and is found mainly in northwest India, Pakistan and Iran (10). Hb D-Punjab is so named because of its higher prevalence in the Punjab region spanning India and Pakistan (2.0% in the Sikh community).…”

“…Hb D-Punjab in the heterozygous state is clinically silent, with variant levels of 540.0%. The blood film may be normal or may show target cells (10).…”