Diagnostic Conundrum: Anemic New born and Identification of Novel Red Cell Gene Mutation Supporting Sideroblastic Anemia

Rapid Communication

Ann Hematol Oncol. 2020; 7(5): 1299.

Diagnostic Conundrum: Anemic New born and Identification of Novel Red Cell Gene Mutation Supporting Sideroblastic Anemia

Islam MS¹* and Hutchens D²

¹Consultant Hematologist, Department of Hematology, Queen Elizabeth and Guy’s Hospital, UK

²Senior Hematology Biomedical Scientist, Special Hematology section, Queen Elizabeth Hospital, UK

*Corresponding author: Serajul Islam, Consultant Hematologist, Department of Hematology, Queen Elizabeth Hospital and Guy’s Hospital, Stadium Road, London, SE18 4QH, UK

Received: April 26, 2020; Accepted: June 08, 2020; Published: June 15, 2020

Abstract

Term newborn usually have a higher Hemoglobin (Hb) compared to older children and adults and majority of their Hb consists of HbF. However, babies born with congenital sideroblastic anemias can be anemic at birth in absence of hemolysis or bleeding complications. Diagnosis can be challenging and Red Cell Gene Panel (RCGP) can be helpful in such circumstances. We report such a newborn here who had low HbF% at birth and he was diagnosed with Autosomal Recessive pyridoxine refractory congenital Sideroblastic Anemia (ARSA) and we identify a novel red cell gene mutation (the SLC25A38 c. 706c>T).

Keywords: Hemoglobin F; Anemia; Red cell gene mutation; Sideroblastic anemia

Introduction

Term newborn usually have a higher Hemoglobin (Hb) compared to older children and adults. This increased Hb is a normal compensatory mechanism in these infants for the relative tissuelevel hypoxia that is prevalent in the intrauterine environment, and it is exacerbated by the high affinity of fetal hemoglobin for oxygen [1,2]. In utero, the oxygen saturation in arterial blood is low and erythropoietin levels are high, hence there is a rapid red blood cell production in fetuses. Soon after birth, the oxygen saturation goes as high as up to 95%, which intern down regulates the erythropoietin mediated red cell production and haemoglobin levels fall [3]. At birth the Hb levels are 149 g/L-237 g/L in term and 191 g/L-221 g/L in preterm babies [4].

Congenital Sideroblastic Anemias are rare disorder caused by mutations in genes that are involved in heme synthesis, iron-sulfur cluster biogenesis, or mitochondrial metabolism [5]. For heme synthesis, the gene defect is on the x-chromosome, forming mutations in the Aminolevulinate Synthase (ALAS2), Adenosine Triphosphate- Binding Cassette B7 (ABCB7) or Glutaredoxin 5(GRLX5) enzymes. Other causes include mutations in the mitochondrial transporter (SLC25A38), thiamine transporter SLC19A2, RNA modifying enzyme Pseudouridine Synthase (PUS1), mitochondrial Tyrosyl- Trna Synthase (YARS2) and mitochondrial DNA deletions [6].

A male baby born at term underwent blood tests as he was clinically listless. His blood test showed he was anemic but his White Blood Count (WBC) and Platelet counts was normal. His MCV as well as MCH were also exceptionally low. Hemoglobin Electrophoresis (HbE) using high performance liquid chromatography did not show any abnormal Haemoglobin (Hb) but Hishaemoglobin F (HbF) level was much lower than expected at 22.5% for a new born infant (Table 1 & Figure 1). There was no history of intra-uterine bleeding complications or any intra-uterine transfusion which could have explained his low HbF%. His vital parameters remain stable. Neonatologist started him on antibiotic suspecting infection. However, he remained clinically stable but listless and his blood parameters did not improve. Both his parents were physically well, and they had normal blood parameters (Table 2).