NIV Congres

Introduction: Anaemic patients with a decreased mean corpuscular volume (MCV) suggestive for thalassemia can be screened for variants of haemoglobine and most common α-thalassemia deletions. Here we present an unusual 970 bp deletion in the promoter of the α1-globulin gene which would be missed in standard thalassemia screening.

Case: A 68-year old Dutch male was evaluated for microcytic anaemia, detected in regular blood donation screening. Medical history included hypertension, hypothyroidism, duodenal ulcer and stomach perforation without further specific complaints. Laboratory analysis showed a microcytic anaemia (Hb 7.8 mmol/l, MCV 65 fl), a decreased mean corpuscular haemoglobin (MCH 13.3 fmol) and low ferritin (9 ug/l). Iron deficiency was suspected. After iron suppletion, haemoglobin was normalized, but microcytosis continued. Endoscopy of the stomach and CT-colonography showed no abnormalities. Concluding: The patient had a temporary iron deficiency of unknown origin with persisting microcytosis. Standard screening for thalassemias showed no abnormalities. Since the peripheral blood smear showed an abnormal red cell morphology, extended laboratory analysis was performed. DNA sequencing showed an unusual 970 bp deletion in the promoter of the α1-globulin gene.

A literature search resulted in only one case report which described the same 970 bp deletion in another Dutch family. However, in this case all 4 patients had a slightly lower MCV, only the proband had anaemia.

We screened the relatives of our index-patient to investigate whether the deletion was germline or somatically. Two brothers and a sister of the proband carried the same deletion. One had a low MCV, the other two had a normal MCV. All had a decreased MCH. The siblings of the deletion carriers were tested as well. Two of them carried the deletion as well. Probably this deletion may change the phenotype of the red blood cell. Since it does not cause anaemia in our affected family, we consider the deletion of no clinical significance.

Conclusion: A deletion of 970 bp in the promoter of the α1-globuline gene causes an abnormal morphologic blood smear. This deletion is missed using standard methods for thalassemia screening. In contrast to the known case report, we did not see MCV changes suggesting variable phenotypes. Therefore screening for the 970 bp deletion does not seem to have any clinical implications.