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Ann Clin Biochem. 2012 Sep;49(Pt 5):445-9. doi: 10.1258/acb.2012.011234. Epub 2012 Jul 24.

A spurious haemoglobin A(1c) result associated with double heterozygote for haemoglobin Raleigh (β1[NA1]Val → Ala) and α(+)-thalassaemia.

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The Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand.



Accurate measurement of haemoglobin A(1c) (HbA(1c)) is useful for long-term glycaemic control in patients with diabetes. Many Hb variants can interfere with HbA(1c) measurement and cause inaccurate results.


The subject was a 31-year-old Thai man who was discovered because of an unexpected HbA(1c) result; other diabetic parameters were within the normal range. Abnormal Hb was investigated using automated high-pressure liquid chromatography (HPLC) and a capillary electrophoresis system. Mutation analysis was done by cDNA sequencing, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex allele-specific PCR assays.


Evaluation of HbA(1c) by cation-exchange HPLC showed a value of 34.9% (reference interval, 4.0-6.0%), but a value of only 4.0% (reference value, 4.8-5.9%) was found with a turbidimetric immunoassay. Haematological analysis revealed a mild anaemia but other parameters were within the normal range. Hb-HPLC analysis demonstrated an unknown Hb variant (47.0%) separating from HbA (46.7%), but capillary electrophoresis identified no abnormal peaks. Mutation analysis identified the Hb Raleigh (β1[NA1]Val → Ala [GTG → GCG]) mutation in combination with an α(+)-thalassaemia, a hitherto undescribed association. The Hb Raleigh mutation could be detected by PCR-RFLP or a multiplex allele-specific PCR assay.


Hb Raleigh can cause falsely increased HbA(1c) values on cation-exchange HPLC. Definitive diagnosis of this variant using combined Hb and DNA analyses is therefore essential.

[Indexed for MEDLINE]

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