A case report of congenital sideroblastic anemia caused by a novel ALAS2 mutation in conjunction with thalassemia.

backgroundCongenital sideroblastic anemia (CSA) and thalassemia are both hereditary disorders of erythropoiesis, primarily affecting erythroid cells. Their typical manifestations include anemia and iron overload. In this study, we conducted clinical and molecular analyses on a male patient who was concurrently diagnosed with thalassemia and CSA.

methodsThe patient underwent a series of tests including complete blood count, bone marrow smear, and serum ferritin levels. Whole exome sequencing technology was employed for genetic mutation analysis, and bioinformatics methods were utilized to assess the functional impact of the predicted variants.

resultsThe patient was previously diagnosed with alpha thalassemia (with genotype of --SEA/-α4.2), and has been receiving frequent blood transfusions over the past two years, presenting with severe anemia (Hb level of 44 g/L), iron overload, and 52% ring sideroblasts in the bone marrow. Whole exome sequencing revealed a hemizygous nonsense mutation (c.224 C > A) in the 5-aminolevulinate synthase (ALAS2) gene, which introduces a premature stop codon at the 75th amino acid position in the N-terminal region (P.S75X). Family analysis showed that the patient, her mother, and her sister all carry this variant, suggesting it is a de novo mutation. Computational analysis using various online software tools predicted the variant to be deleterious. The patient was treated with a combination of vitamin B₆, folic acid, and deferasirox. After six months, the Hb level increased to 104 g/L, while the serum ferritin level initially rose and subsequently decreased.

conclusionThis study identified and reported a novel variant, ALAS2 c.224 C > A (P.S75X), which led to the co-occurrence of sideroblastic anemia in a male patient with thalassemia. The anemia symptoms induced by this variant were responsive to pyridoxine (vitamin B₆) supplementation therapy.