Hemoglobin Variants: Biochemical Properties and Clinical Correlates

Abstract

Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples.

Unusually Low Oxyhemoglobin Saturation on Polysomnography

“…Although there are more than 1,000 known hemoglobin variants, low-oxygen affinity variants that are associated with low SpO 2 are infrequent. 6,7 Patients with low-oxygen affinity variant hemoglobin may be completely asymptomatic or present with cyanosis but may otherwise be clinically well. 6,8 Our patient's mother carried a diagnosis of hemoglobin Denver.…”

Classification of the Disorders of Hemoglobin

“…Most patients with b-thalassemia intermedia carry two mutant b-globin genes: they have a genotype typical of b-thalasemia major, but the phenotype is modified by one of the factors listed above. However, rare cases of b-thalassemia intermedia are caused by heterozygosity for a single mutant b-globin gene associated with the production of a highly unstable b-globin subunit that causes RBC damage in a fashion similar to excess free a-subunits; this is the so-called "dominant b-thalassemia" (Thom et al 2013).…”

“…As discussed briefly here, and in much more detail in Thein (2013), Higgs (2013), Nienhuis and Nathan (2012), and Musallam et al (2012), mutations of globin genes that impair synthesis give rise to thalassemia and anemia of varying degree. In addition, well-defined clinical and hematologic phenotypes are associated with mutations that alter the structure of globin subunits, discussed in more detail in Thom et al (2013). Impairment of hemoglobin solubility can be caused either by the formation of intracellular polymers (sickle cell disease) or by the development of amorphous precipitates (congenital Heinz body hemolytic anemia).…”

"Analysis of Haemoglobin Variants and Oxygen Affinity in Indian and Kyrgyz Population Groups"

“…It's a good indicator of long-term glycemic control. Hemoglobinopathies like thalassemia and sickle cell anaemia can be tested using High Performance Liquid Chromatography (HPLC), isoelectric focusing and spectroscopy and are the Original Article most commonly used routine tests to identify structurally abnormal haemoglobin variants (1,3). HbA 2 is increased in people with thalassemia.…”