Severe hereditary haemolytic anaemia in a Caucasian newborn: a new fetal haemoglobin variant Hb F-Bonheiden (Gγ 38(C4) Thr→Pro)

Abstract

We report on the identification of a new c chain variant, HbF-Bonheiden (c38(C4) Thr fi Pro), found in a male Caucasian newborn, exhibiting a severe nonspherocytic haemolytic anaemia. The baby was born after a full-term pregnancy from apparently healthy parents. Two weeks after birth, he presented with acute pallor and a very low haemoglobin level of 4.3 g/dl. Red blood cell indices were normal. Reticulocytosis was increased with a negative direct antiglobulin test. The peak level of bilirubin was 9.4 mg/ dl. The activity of red cell enzymes was reported as normal. Heinz bodies were absent. Haemoglobin electrophoresis showed no abnormal fractions, but exhibited a markedly decreased HbF level (±20%) [1]. After transfusion, the haemoglobin level decreased again progressively until the 50th day and the anaemia resolved spontaneously thereafter. The family history revealed that the father also needed postnatal transfusion. Moreover, the brother of the father died 6 days after birth. Sequencing of the c-globin genes disclosed an A fi C mutation in a heterozygote state at the codon 38 level which implies a Thr fi Pro substitution. The sister, the father and the paternal grandmother (Fig. 1) carried the same point mutation. This genetic abnormality has never been described in the c-globin gene. However, in the b-globin gene, a similar mutation is known as an unstable haemoglobin variant, named Hb Hazebrouck (b38(C4) Thr fi Pro), also associated with haemolytic anaemia [2]. At the level of the c-gene, a four base pair deletion in the promoter region (-222 tot 225) was found, which was only detected in the mother’s DNA (Fig. 1) [3]. In contrast to a and b chain abnormalities, c chain variants have seldom been reported and only a few have clinical implications http://globin.cse.psu.edu. HbFPoole was the first observation of an unstable HbF variant associated with haemolytic anaemia in the newborn period [5]. Methaemoglobin formation is found in HbF-M-Osaka and in HbF-M-Fort Ripley http://globin.cse.psu.edu. HbF-Cincinnati causes cyanosis because of low oxygen affinity [4]. This case illustrates that fetal haemoglobin variants should be included in the differential diagnosis of unexplained anaemia in the newborn. M. Van den Driessche (&) Æ J. Moerman Æ M. Moens Laboratory of Clinical Biology, Imelda Hospital, Imeldalaan 9, 2820 Bonheiden, Belgium E-mail: marleen.vd.driessche@imelda.be Tel.: +32-15-505469 Fax: +32-15-505479

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