Molecular Characterization and Hematological Aspects of Hb E-Myanmar [ß26(B8)Glu→Lys and ß65(E9)Lys→Asn, HBB: c.[79G>A;198G>C]): A Novel ß-Thalassemic Hemoglobin Variant.

Hb E [ß26(B8)Glu→Lys, GAG>AAG, HBB: c.79G>A] is an inherited thalassemic ß-globin variant that favors the Hb E-ß-thalassemia (ß-thal) syndrome when interacting with the ß-thal gene. However, hemoglobin (Hb) variants carrying Hb E in combination with another variant on the same ß gene are rare. We recently studied a 29-year-old pregnant woman, initially diagnosed as a ß-thal carrier. Hemoglobin and DNA analysis were performed by high performance liquid chromatography (HPLC) and DNA sequencing. Hematological data revealed no anemia or altered red blood cell (RBC) parameters. Hemoglobin HPLC showed Hb A and Hb A2 but no Hb E or abnormal Hb peaks, with a markedly elevated Hb A2 level (6.4%) reaching the accepted range (4.0-10.0%) for ß-thal trait. DNA analysis identified a GAG>AAG transition at codon 26 of the ß-globin gene that is responsible for Hb E, and an AAG>AAC mutation at codon 65 in cis on the ß-globin chain resulting in a lysine to asparagine substitution. These two mutations led to the formation of a novel variant, namely Hb E-Myanmar, ß26(B8)Glu→Lys and ß65(E9)Lys→Asn, HBB: c.[79G>A;198G>C]. Moreover, a heterozygous α-thalassemia-2 (α-thal-2) [-α3.7 (rightward)] deletion was also observed. Hb E-Myanmar is a doubly substituted ß-globin variant, which has not been previously described. This variant did not have any clinical or hematological abnormalities, and the genetic mechanism resulting in this variant is discussed. The new simultaneous allele-specific polymerase chain reaction (ASPCR) was developed for rapid detection of these two mutations within the same ß-globin chain.

PERSONAL AND ENVIRONMENTAL RISK FACTORS SIGNIFICANTLY ASSOCIATED WITH ELEVATED BLOOD LEAD LEVELS IN RURAL THAI CHILDREN.

A community-based study was conducted to determine personal risk factors and environmental sources of lead exposure for elevated blood lead levels (≥ 10 µg/dl, EBLLs) among rural children living at the Thailand-Myanmar border in Tak Province, northwestern Thailand. Six hundred ninety-five children aged 1-14 years old were screened for BLLs. Environmental specimens for lead measurements included samples of water from the streams, taps, and household containers, house floor dust, and foods. Possible lead release from the cooking ware was determined using the leaching method with acetic acid. The overall prevalence of EBLLs was 47.1% and the geometric mean level of blood lead was 9.16 µg/dl. Personal risk factors significantly associated with EBLLs included being male, younger age, anemia, and low weight-for-age. Significant environmental risk factors were exposure to a lead-acid battery of solar energy system and use of a non-certified metal cooking pot. Some families whose children had high BLLs reported production of lead bullets from the used batteries at home. About one-third of the house dust samples taken near batteries contained lead content above the recommended value, compared with none of those taken from other areas and from the houses with no batteries. The metal pots were safe for cooking rice but might be unsafe for acidic food preparation. Both nutritional intervention and lead exposure prevention programs are essential to reduce EBLLs in this population.