Submitted September 13, 2002
Accepted January 13, 2003
Late-onset X-linked sideroblastic anemia following hemodialysis
Kazumichi Furuyama*, Hideo Harigae, Chiharu Kinoshita, Toshihiko Shimada, Kazuko Miyaoka, Chiaki Kanda, Yoshifumi Maruyama, Shigeki Shibahara, and Shigeru Sassa
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Japan
Department of Molecular Diagnostics, Tohoku University School of Medicine, Sendai, Japan
Kyoto Min-I-Ren Central Hospital, Kyoto, Japan
Maruyama Clinic, Kyoto, Japan
Department of Biochemical Hematology, The Rockefeller University, New York, NY, USA
* Corresponding author; email: k-furuya{at}mail.cc.tohoku.ac.jp.
X-linked sideroblastic anemia (XLSA) is due to deficient activity of erythroid-specific 5-aminolevulinate synthase (ALAS2). We report here a patient who developed sideroblastic anemia at the age of 81 while undergoing hemodialysis. The diagnosis of sideroblastic anemia was established by the presence of ringed sideroblasts in the bone marrow, and treatment with oral pyridoxine completely eliminated the ringed sideroblasts. We identified a novel point mutation in the 5th exon of this patient's ALAS2 gene, which resulted in an amino acid change at residue 159 from aspartic acid to asparagine (D159N). In vitro analyses of recombinant D159N ALAS2 revealed that this mutation accounted for the pyridoxine-responsiveness of his disease. The very late onset in this case of XLSA emphasizes that nutritional deficiencies caused either by dietary irregularities in the elderly or, as in this case, by maintenance hemodialysis therapy, may uncover occult inherited enzymatic deficiencies in the heme biosynthetic pathway.
