Severe Microcytic Anemia Caused by Complex Hereditary Spherocytosis and X-Linked Sideroblastic Anemia with Mutations in SPTB and ALAS2 Genes

We report a case of severe anemia caused by complex hereditary spherocytosis (HS) and X-linked sideroblastic anemia (XLSA) with two mutations in the spectrin beta (SPTB) and 5-aminolevulinic acid synthase (ALAS2) genes. The proband was a 16-year-old male with severe jaundice and microcytic hypochromic anemia since his childhood. He had more severe anemia requiring erythrocyte transfusion, and had no response to vitamin B-6 treatment. Next-generation sequencing (NGS) revealed double heterozygous mutations, one in exon 19 (c.3936G > A:p.W1312X) of the SPTB gene and another in exon 2 (c.37A > G:p.K13E) of the ALAS2 gene, and confirmed again by Sanger sequencing. The mutation of ALAS2 (c.37A > G) is inherited from his asymptomatic heterozygous mother, causing amino acid p.K13E, and the mutation has not yet been reported. The mutation of SPTB (c.3936G > A) is a nonsense mutation, leading to a premature termination codon in exon 19, and the mutation in the SPTB gene is not found in any of his relatives, which indicates a de novo monoallelic mutation. Conclusions: The double heterozygous mutations in the SPTB and ALAS2 genes lead to the joint occurrence of HS and XLSA in this patient, and are implicated in the more severe clinical phenotypes.

Automated summary

We present a case of severe anemia in a 16-year-old male with complex hereditary spherocytosis (HS) and X-linked sideroblastic anemia (XLSA) caused by mutations in the spectrin beta (SPTB) and 5-aminolevulinic acid synthase (ALAS2) genes. Next-generation sequencing revealed double heterozygous mutations in exon 19 of the SPTB gene (c.3936G > A:p.W1312X) and exon 2 of the ALAS2 gene (c.37A > G:p.K13E). The mutations were confirmed by Sanger sequencing. The mutations in the SPTB and ALAS2 genes contribute to the more severe clinical phenotypes observed in this patient.