Hemoglobin (Hb) Stanleyville II Causes Gross Overestimation of the Hb A1c Proportion in Routine HPLC

Homozygous Hb Stanleyville-II [alpha2 78(EF7) Asn>Lys; HBA2:c.237C>A, not C>G] associated with genotype −α3.7/−α3.7 in two Brazilian families

“…, 2000), the AAC>AAA mutation was said to be associated with the −α 3.7 deletion. In all three types of −α 3.7 deletion, the second exon of the α1 gene is located in the fragment that is lost during the crossing‐over that generates the hybrid gene, and so the mutation was indeed in the α2 rather than in α1 gene, as recognized by the same authors in a subsequent report; (ii) The second report that the mutation would be located in the α1 gene (Ostendorf et al. , 2005) is doubtful because the reverse primer used in that study for genomic amplification and subsequent sequencing is α2‐gene specific, as can be checked in the NCBI sequence; (iii) In the third study (Moradkhani et al.…”

“…, 2007; Burchall & Maxwell, 2010), Europe (Gonzalez et al. , 2008; Ostendorf et al. , 2005), and Brazil (Costa et al.…”

Hb Stanleyville-II [α78(EF7)Asn→Lys (α2); HbA2: c.237C>A]: Incidence of 1:11,500 in a Newborn Screening Program in Brazil

“…This Hb was first described in the Democratic Republic of Congo (1). There are also cases reported in other African countries (8,13,14), Europe (7,15), China (12), and Brazil (3)(4)(5)9,11,16,17).…”

“…All mutations were found on the α2 or hybrid Àα 3.7 gene, never on the α1 gene. The mutation that encodes Hb Stanleyville-II has been described on the α1 gene in some studies (11,12,15,23), but the results may have been misinterpreted by some authors (5). It is possible that the mutation has arisen on different genes depending on ethnicity (12).…”

QA aspects for HbA1c measurements

“…HPLC methods show interference from coelution of the hemoglobin variant with either HbA 1c or HbA or inadequate resolution of the variant from HbA [13,14]. The presence of HbF can interfere with HbA 1c measurements by boronate affinity and immunoassay methods producing falsely low results [15].…”