X-linked pyridoxine-responsive sideroblastic anemia due to a Thr388-to-Ser substitution in erythroid 5-aminolevulinate synthase

Background X-linked sideroblastic anemia is usually associated with reduced 5-aminolevulinate synthase activity in erythroid cells, and some cases are responsive to treatment with pyridoxine, the precursor to the cofactor of the enzyme. The recently identified gene for an erythroid-specific 5-aminolevulinate synthase isoenzyme and its localization to the X chromosome make it likely that one or more defects in this gene underlie the anemia. Methods Using a polymorphic dinucleotide-repeat sequence in the erythroid 5-aminolevulinate synthase gene, we confirmed the linkage of this gene to the disorder in a family with X-linked pyridoxine-responsive sideroblastic anemia. We therefore sought evidence of a nucleotide-sequence abnormality in the erythroid 5-aminolevulinate synthase gene by analyzing enzymatically amplified DNA. Results DNA-sequencing studies in two affected males and one carrier female in the kindred demonstrated a cytosine-to-guanine change at nucleotide 1215 (in exon 8). This change results in ...