A Case of a Successful Gestation in a Patient with an Unclassified Transfusion Dependent Congenital Dyserythropoietic Anemia and Hemoglobinopathy

doi:10.13188/2380-6842.1000021

Abstract

Highlights

Congenital Dyserythropoietic Anemias (CDAs) are rare congenital disorders, characterized by mild to severe ineffective erythropoiesis [1,2]
Given the atypical features of this case, such as the severity of anemia and autosomal dominant inheritance pattern, additional genomic analysis was performed on both the patient and her offspring (Figure 2). Exome sequencing for both individuals was negative for any known mutation for CDA, including SEC23B, but evaluation for hemoglobinopathy was significant for a novel heterozygous mutation of the HBB gene, an insertion at position 409 to 417 leading to an additional glycine-alanine-alanine chain in both individuals
In pregnant patients with severe anemia, hemoglobin of less than 6 g/dL has been linked to intrauterine growth restriction, low fetal birth weight, prematurity, and neonatal death [7,8,9,10]

Summary

Introduction

Congenital Dyserythropoietic Anemias (CDAs) are rare congenital disorders, characterized by mild to severe ineffective erythropoiesis [1,2]. Fetal ultrasounds demonstrated normal fetal anatomy; by the 3rd trimester the fetus had developed Intrauterine Growth Restriction (IUGR) She required approximately 2 units PRBC transfusions every 2 weeks to maintain her hemoglobin above 6 g/dL. Given the atypical features of this case, such as the severity of anemia and autosomal dominant inheritance pattern, additional genomic analysis was performed on both the patient and her offspring (Figure 2) Exome sequencing for both individuals was negative for any known mutation for CDA, including SEC23B, but evaluation for hemoglobinopathy was significant for a novel heterozygous mutation of the HBB gene, an insertion at position 409 to 417 leading to an additional glycine-alanine-alanine chain in both individuals. This particular hemoglobinopathy has not been described previously to be expressed in combination with any of the known types of CDA but may contribute to this severe phenotype [1]

Discussion

Conclusion