Characterization of hemoglobin bassett (α94Asp→Ala), a variant with very low oxygen affinity

Abdulmalik, Osheiza; Lerner, Norma B.; Ochotorena, Josiree; Daikhin, Evgueni; Lakka, Vinaysagar; Santacroce, Rosa; Abraham, Donald J.; Asakura, Toshio

doi:10.1002/ajh.20184

Cited by 28 publications

(19 citation statements)

References 30 publications

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“…In this instance, the P 50 of the whole blood was normal (28 mm Hg), likely due to the fact that only a small proportion of the total hemoglobin was Hb Bassett. In another report, Hb Bassett accounted for 30% of the total hemoglobin [15], suggesting that the mutation resided on an α2‐globin gene [18]. In this study, P 50 measurement on isolated Hb Bassett was high (22 mm Hg; normal p50 for Hb A 10.5 mm Hg), consistent with the variant hemoglobin having low oxygen affinity.…”

Section: Resultssupporting

confidence: 77%

“…There were five publications of patients who were carriers of either Hb Bassett [10,15], Hb Rothschild [2,5], or Hb Canebiere [17] (Supporting Information—Table I). These are low oxygen affinity variant hemoglobins [15–17]. There was one report on each of these three variant hemoglobins showing low SpO 2 and similarly low SaO 2 .…”

Section: Resultsmentioning

confidence: 99%

“…There was one report on each of these three variant hemoglobins showing low SpO 2 and similarly low SaO 2 . In three of these cases [5, 15, 17], the PaO 2 was normal, indicating that there was no apparent tissue hypoxemia.…”

Section: Resultsmentioning

confidence: 99%

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Unexpectedly low pulse oximetry measurements associated with variant hemoglobins: A systematic review

et al. 2010

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Pulse oximetry estimates arterial blood oxygen saturation based on light absorbance of oxy‐ and deoxy‐hemoglobin at 660 and 940 nm wavelengths. Patients with unexpectedly low SpO2 often undergo cardio‐pulmonary testing to ascertain the cause of their hypoxemia. However, in a subset of patients, a variant hemoglobin is responsible for low SpO2 measurements. The extent of this problem is unclear. We performed a systematic literature review for reports of low SpO2 associated with variant hemoglobins. We also reviewed unpublished cases from an academic hemoglobin diagnostic reference laboratory. Twenty‐five publications and four unpublished cases were identified, representing 45 patients with low SpO2 and confirmed variant hemoglobin. Fifty‐seven family members of patients had confirmed or suspected variant hemoglobin. Three low oxygen affinity variant hemoglobins had concordantly low SpO2 and SaO2. Eleven variant hemoglobins were associated with unexpectedly low SpO2 measurements but normal SaO2. Hemoglobin light absorbance testing was reported in three cases, all of which showed abnormal absorption spectra between 600 and 900 nm. Seven other variant hemoglobins had decreased SpO2, with unreported or uncertain SaO2. Twenty‐one variant hemoglobins were found to be associated with low SpO2. Most variant hemoglobins were associated with spuriously low SpO2. Abnormal absorption spectra explain the discrepancy between SpO2 and SaO2 for some variants. The differential diagnosis of possible variant hemoglobin ought to be considered in asymptomatic patients found to have unexpectedly low SpO2. The correct diagnosis will help to spare patients from unnecessary investigations and anxiety. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.

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Section: Resultssupporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

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Unexpectedly low pulse oximetry measurements associated with variant hemoglobins: A systematic review

et al. 2010

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“…For example, removal of the exocyclic amine in the minor groove of P1 (U12-A127) and the major groove of P3a stem (G67-U77) in aptamer 1 caused decreased affinity and cooperativity. The hemoglobin mutant Bassett (aAsp94 / Ala) showed similar results with reduced binding affinity and cooperativity (Abdulmalik et al 2004). Crystallographic structures of hemoglobin Bassett revealed that disruption of a hydrogen bond in the a1/b2 interface of the R state is responsible for this effect (Safo et al 2005).…”

Section: Comparison With Cooperativity In Hemoglobinmentioning

confidence: 64%

Chemical basis of glycine riboswitch cooperativity

Kwon¹,

Strobel²

2007

RNA

118

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The glycine binding riboswitch forms a unique tandem aptamer structure that binds glycine cooperatively. We employed nucleotide analog interference mapping (NAIM) and mutagenesis to explore the chemical basis of glycine riboswitch cooperativity. Based on the interference pattern, at least two sites appear to facilitate cooperative tertiary interactions, namely, the minor groove of the P1 helix from aptamer 1 and the major groove of the P3a helix from both aptamers. Mutation of these residues altered both the cooperativity and binding affinity of the riboswitch. The data support a model in which the P1 helix of the first aptamer participates in a tertiary interaction important for cooperativity, while nucleotides in the P1 helix of the second aptamer interface with the expression platform. These data have direct analogy to well-characterized mutations in hemoglobin, which provides a framework for considering cooperativity in this RNA-based system.

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“…Low oxygen affinity Hb variants will typically have low SpO 2 readings accompanied by low SaO 2 , with no evidence of cardiac or respiratory disease . Examples of such Hbs include Hb Bassett, Hb Rothschild and Hb Canebiere . There are also a subset of low affinity variants with low SpO 2 and normal SaO 2 (eg, Hb Titusville and Hb Bonn) .…”

Section: Diagnostic Testsmentioning

confidence: 99%

How we diagnose and manage altered oxygen affinity hemoglobin variants

Yudin

Verhovsek

2019

American J Hematol

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Altered oxygen affinity variant hemoglobins (Hbs) are caused by mutations of the globin genes.Changes in Hb oxygen affinity shift the oxygen dissociation curve, and can be identified by abnormal p50 measurements of patient red blood cells. Variants are categorized as either low oxygen affinity (high p50) or high oxygen affinity (low p50). Accurate diagnosis requires recognition of typical clinical and laboratory findings. In this case-based review, we present two patients with altered oxygen affinity variants, illustrating barriers to prompt and accurate diagnosis, and issues in management. We then review pathophysiology, diagnostic tests, clinical features, and management strategies.

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Characterization of hemoglobin bassett (α94Asp→Ala), a variant with very low oxygen affinity

Cited by 28 publications

References 30 publications

Unexpectedly low pulse oximetry measurements associated with variant hemoglobins: A systematic review

Unexpectedly low pulse oximetry measurements associated with variant hemoglobins: A systematic review

Chemical basis of glycine riboswitch cooperativity

How we diagnose and manage altered oxygen affinity hemoglobin variants

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