Identification of a Hemizygous R170H Mutation in the ALAS2 Gene in a Young Male Patient with X-linked Sideroblastic Anemia

Hee-Suk Choung; Hee-Jin Kim; Chul Won Jung; Sun-Hee Kim

doi:10.5045/kjh.2008.43.2.118

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Choung, Kim, Jung, and Kim: Identification of a Hemizygous R170H Mutation in the ALAS2 Gene in a Young Male Patient with X-linked Sideroblastic Anemia

Case Report

Korean J Hematol 2008;43(2):118-121.

Published online: 19 June 2008

DOI: https://doi.org/10.5045/kjh.2008.43.2.118

Identification of a Hemizygous R170H Mutation in the ALAS2 Gene in a Young Male Patient with X-linked Sideroblastic Anemia

Hee-Suk Choung¹, Hee-Jin Kim¹, Chul Won Jung², Sun-Hee Kim^1,

¹Department of Laboratory Medicine and Genetics, Seoul, Korea

²Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Correspondence to：Sun-Hee Kim, M.D. Departments of Laboratory Medicine, Samsung Medical Center 50, Ilwon-dong, Gangnam-gu, Seoul 135-710, Korea Tel: ＋82-2-3410-2704, Fax: ＋82-2-3410-2719 E-mail: sunnyhk@skku.edu

Received 21 April 2008 Revised 27 May 2008 Accepted 30 May 2008

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

X-linked sideroblastic anemia (XLSA) is a rare hereditary disease characterized by microcytic hypochromic anemia, ineffective erythropoiesis and the presence of numerous ringed sideroblasts in the bone marrow. The causative gene is the erythroid δ-aminolaevulinate synthase 2 gene (ALAS2) on Xp11.21. We report here a case of XLSA. The patient was a 20-year-old Korean man referred to our hospital under the impression of sideroblastic anemia (SA). Laboratory findings, including a peripheral blood smearand bone marrow study, were compatible with SA. The family history was not remarkable. Based on the early age of onset, we suspected a hereditary form of SA, particularly XLSA. Direct DNA sequencing of ALAS2 detected a hemizygous c.509G＞A (R170H) mutation in exon 5 of the gene. The patient showed minimal response to pyridoxine treatment. To the best of our knowledge, this is the first case of genetically confirmed XLSA from a mutation in ALAS2 in Korea.

Keywords: X-linked sideroblastic anemia, ALAS2, Mutation, R170H, Korea

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Fig. 1

(A) Peripheral blood smear of the patient showed microcytic hypochromic anemia with dimorphism and anisopoikilocytosis (Wright-Giemsa stain, ×400). (B) The bone marrow aspirate smear showed mild erythroid dysplasia such as internuclear bridging (Wright-Giemsa stain, ×1,000). (C) Ringed sideroblasts were frequently observed (arrow) and were counted up to 30∼40% of normoblasts on bone marrow aspirate smear (Prussian blue stain, ×1,000).

Fig. 2

Direct sequencing of the ALAS2 gene detected a hemizygous c.509G＞A mutation (red box) in exon 5, which was predicted to substitute the highly conserved arginine residue at codon 170 with histidine (p.R170H).

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