Haemoglobinopathy as a cause of nucleated red cells in the fetus and neonate

Editor—We are interested in the article by Hermansen1 on the causes of peripheral nucleated red blood cells in newborn children and would add another differential diagnosis to this finding.

In the last decade, we have discovered two families affected by haemoglobin disorders where the diagnosis was suspected by the presence of high numbers of nucleated red cells in neonatal blood tests. In neither family was the potential for significant haemoglobin disorders suspected. The families concerned were Indian Asian in origin and the marriages were consanguineous. The children now present with thalassaemia intermedia, but because of the difficulty in predicting the clinical course of these disorders, it is not yet clear whether they will become transfusion dependant, although this is highly likely for two individuals, one in each family.

The first recognised child in Family 1 was born in 1991. A blood test performed because of jaundice on the third day of life showed 160NRBC/100WBC. Other causes of erythroblastosis were excluded. Haemoglobin analyses on the parents showed that the mother was heterozygous for Indian inversion/deletion db-thalassaemia, while the father was a compound heterozygote for db-thalassaemia and Haemoglobin Headington.2 This child and two other children are homozygous for db-thalassaemia. The eldest child seems more severely affected and has been transfused twice, following infections.

The second family presented in 1996 when their first son was found at birth to have 2000NRBC/100 WBC. Other causes having been excluded, haemoglobin studies revealed only the existence of b-thalassaemia trait (codon 16bO) in the father. The boy is now anaemic, has thalassaemic bossing of the skull and splenomegaly, and looks as if he will need a transfusion programme. A brother, born in 1999, had 983NRBC/100WBC in his initial blood test, and has also inherited his father's haemoglobin pattern. It is likely that this family is showing dominant b-thalassaemia,3 although recent studies suggest there may be a coinherited aldolase deficiency, akin to aldolase, from the mother. (J Porter, personal communication).

We hope this report may help in the investigation of other families.