Increasing recognition of haemoglobin Le Lamentin

• haemoglobin variant
• Le Lamentin

The haemoglobin variant Le Lamentin (α20 His → Gln) was first described in 1982 in a negro family in the French West Indies.¹ Subsequently, it has been reported in a Japanese family² and in a Spanish family,³ and recently it was found in a British white man whose haemoglobin displayed an unusual peak when his blood was being assayed for glycated haemoglobin (haemoglobin A_1c) by high performance liquid chromatography (HPLC).⁴

Using a similar technique for HbA_1c, we have also found a case in the UK. The patient is a 46 year old diabetic woman with a plasma glucose of 11.2mmol/litre and HbA_1c of 5.5% (reference range, 3.8–5.5%), with a haemoglobin trace on a Menarini HA-8121 analyser that exhibited an unusual early eluting fraction. This, together with our feeling that the HbA_1c was rather low for the plasma glucose, raised our suspicions that a haemoglobin variant might be present. Therefore, we subjected the blood sample to electrospray ionisation tandem mass spectrometry, as described previously.⁴ This revealed that the patient was heterozygous for the Le Lamentin mutation involving substitution of histidine by glutamine at position 20 on one of the α-chains of haemoglobin. Although the patient's family is based in the north west of England, she says there is a link with Romany gypsies several generations ago, but we did not feel there was sufficient clinical justification for a detailed family study.

Since this finding, we have become aware of three other cases in the UK, making five in all, suggesting that this variant might not be as rare as had hitherto been presumed. Because it seems to have no clinical or haematological consequences in the heterozygous state, becoming apparent only when haemoglobin is subjected to certain ion exchange or isoelectric focusing procedures, its existence may have gone unrecognised. However, it does have implications for the monitoring of glycaemic control by HbA_1c because the HbA_1c result is likely to be affected to an indeterminate degree, making comparison with normal reference ranges erroneous. As long as this is appreciated and taken into account, it should still be possible to use HbA_1c to follow changes in an individual's glycaemic control, so that improvement or worsening can be detected.