Journal
ACTA HAEMATOLOGICA
Volume 125, Issue 4, Pages 193-197Publisher
KARGER
DOI: 10.1159/000322870
Keywords
ALAS2; Pyridoxine responsiveness; X-linked sideroblastic anemia
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Funding
- Ministry of Health, Czech Republic [NS10281-3/2009]
- Ministry of Education, Youth and Sport, Czech Republic [MSM 6198959205]
- Palacky University Olomouc [LF_2010_013]
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Background/Aims: Congenital sideroblastic anemias (SA) are characterized by the presence of ringed sideroblasts in the bone marrow. The most common form is X-linked SA, which results from mutations in erythroid-specific delta-aminolevulinate synthase (ALAS2), the first enzyme in heme biosynthesis. In addition, autosomal recessive mutations in the erythroid-specific mitochondrial transporter SLC25A38 and glutaredoxin 5 (GLRX5) have recently been identified in SA patients with isolated erythroid phenotype. Materials and Methods: We studied 5 young males with congenital SA from the Czech Republic. Mutation analysis was performed on the complete coding regions of 3 candidate genes (ALAS2, SLC25A38 and GLRX5), and the enzyme activity of ALAS2 was measured by a continuous spectrophotometric assay. Results: We found the previously published R452H and R452C ALAS2 mutations in 3 patients. A novel K156E substitution in ALAS2 was discovered in 1 pyridoxine-responsive patient. The functional study showed that this substitution severely decreases ALAS2 enzyme activity. In 1 pyridoxine-refractory patient, no mutations were detected in ALAS2, SLC25A38 or GLRX5. Conclusion: Our report extends the list of known ALAS2 mutations, with the addition of a novel K156E substitution that is responsive to pyridoxine treatment and contributes to the general knowledge of congenital SA cases characterized worldwide. Copyright (C) 2011 S. Karger AG, Basel
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