New mutation in erythroid-specific delta-aminolevulinate synthase as the cause of X-linked sideroblastic anemia responsive to pyridoxine

Acta Haematol. 2011;125(4):193-7. doi: 10.1159/000322870. Epub 2011 Jan 20.


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 δ-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Aminolevulinate Synthetase / genetics*
  • 5-Aminolevulinate Synthetase / metabolism
  • Adult
  • Anemia, Sideroblastic / drug therapy
  • Anemia, Sideroblastic / enzymology
  • Anemia, Sideroblastic / genetics
  • Base Sequence
  • Genetic Diseases, X-Linked
  • Humans
  • Male
  • Mutation
  • Pyridoxine / therapeutic use
  • Sequence Alignment


  • 5-Aminolevulinate Synthetase
  • ALAS2 protein, human
  • Pyridoxine

Supplementary concepts

  • X-linked sideroblastic anemia