Late-onset X-linked sideroblastic anemia following hemodialysis.
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 years 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 fifth exon of this patient's ALAS2 gene, which resulted in an amino acid change at residue 159 from aspartic acid to asparagine (Asp159Asn). In vitro analyses of recombinant Asp159Asn ALAS2 revealed that this mutation accounted for the pyridoxine-responsiveness of this 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.
Furuyama
Kazumichi
K
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Japan. k-furuya@mail.cc.tohoku.ac.jp
Harigae
Hideo
H
Kinoshita
Chiharu
C
Shimada
Toshihiko
T
Miyaoka
Kazuko
K
Kanda
Chiaki
C
Maruyama
Yoshifumi
Y
Shibahara
Shigeki
S
Sassa
Shigeru
S
D000624:5-Aminolevulinate Synthetase / Q000235:genetics; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000756:Anemia, Sideroblastic / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D004252:DNA Mutational Analysis; D005091:Exons; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D008297:Male; D009752:Nutritional Status; D017354:Point Mutation; D011736:Pyridoxine / Q000627:therapeutic use; D006435:Renal Dialysis / Q000009:adverse effects*
D000624:5-Aminolevulinate Synthetase; D011736:Pyridoxine