Severe Microcytic Anemia Caused by Complex Hereditary Spherocytosis and X-Linked Sideroblastic Anemia with Mutations in and 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 ( and 5-aminolevulinic acid synthase () 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 treatment. Next-generation sequencing (NGS) revealed double heterozygous mutations, one in exon 19 (c.3936G > A:p.W1312X) of the gene and another in exon 2 (c.37A > G:p.K13E) of the gene, and confirmed again by Sanger sequencing. The mutation of (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 (c.3936G > A) is a nonsense mutation, leading to a premature termination codon in exon 19, and the mutation in the gene is not found in any of his relatives, which indicates a de novo monoallelic mutation. Conclusions: The double heterozygous mutations in the and genes lead to the joint occurrence of HS and XLSA in this patient, and are implicated in the more severe clinical phenotypes.