Hb G Waimanalo [α264(E13)Asp→Asnβ2] was first observed in members of a Filipino family (1). This variant has also been found in a compound heterozygote simultaneously presenting Hb D-Los Angeles (2) and in a child with concomitant homozygous s-thalassemia (s-that) (3).

Alpha 2-globin gene mutation Hb G-Waimanalo: occurrence in combination with alpha-thalassemia-1.

Haemoglobinopathies (thalassaemia and haemoglobin (Hb) variants) are the most common of all inherited monogenic disorders. More than 1800 mutations in alpha or beta globin genes are known to be responsible for haemoglobinopathies.1 The clinical spectrum of haemoglobinopathies is quite heterogeneous and depends on the underlying mutations. Here, we report, a de novo emergence of rare alpha chain variant Hb G-Waimanalo in a sickle cell disease patient.

An 8-year-old Gond tribal girl born from a non-consanguineous marriage was referred to Division of Genetic Disorders at Indian Council of Medical Research-National Institute of Research in Tribal Health (ICMR-NIRTH) for differential diagnosis for haemolytic anaemia. She had a history of severe anaemia (Hb 47 g/L) and frequent bone and joint pain. She also had a history of multiple blood transfusions since the age of 3 years. Her weight was below 3 SD (17 kg). She exhibited pallor, icterus and typical thalassemic facial features with hepatosplenomegaly (spleen 9 cm and liver 5 cm below respective costal margins). Serum bilirubin count was 87.72 µmol/L (direct bilirubin=6.6 µmol/L and indirect bilirubin=81.57 µmol/L). Serum aspartate aminotransferase was 47.3 mg/dL, alanine aminotransferase was 19.6 mg/dL. Serum lactate dehydrogenase levels were also elevated (540 IU/L) suggesting haemolytic anaemia. Direct Coombs test was negative and glucose six phosphate dehydrogenase levels were within normal limits. Cellulose acetate Hb electrophoresis at alkaline pH (8.4) showed the presence of three Hb variants (figure 1A). One faint band was seen just below the HbA band, and other two bands were seen at position corresponding …

https://jcp.bmj.com/content/jclinpath/early/2020/08/19/jclinpath-2020-206589.full.pdf

De novo heterozygous Hb G-Waimanalo (α64(E13)Asp>Asn, CTG>CCG; HBA1:c.193G>A) variant in a sickle cell disease patient of an Indian tribe.

Hemoglobins D-Los Angeles (β 121 Gin) and Aida (α64 Asn) were encountered in an Asian Indian, unassociated with any clinical manifestations. These hemoglobins had normal oxygen affinities and were stable to heat and isopropanol. The ratio of α chain synthesis to β chain synthesis was close to unity. The identical change in isoelectric points of the two variants produced an interesting electrophoretic pattern.The coexistance of more than one hemoglobin variant in an individual or family has provided valuable

G. J. Schmidt

Papers

Hemoglobins AIDA (α64 ASP → ASN) and D-Los Angeles (β121 Glu → Glu) in an Asian-Indian Family