Three siblings with variable degrees of neuromuscular involvement and congenital sideroblastic anemia: A peculiar phenotype and a surprise genotypic explanation

Abstract

Introduction: Congenital sideroblastic anemias (CSAs) are a group of inherited bone‐marrow disorders manifesting with erythroid hyperplasia and ineffective erythropoiesis. Methods: We describe a detailed clinical and genetic characterization of three siblings with CSA. Results: Two of them had limb‐girdle myopathy and global developmental delay. The two elder siblings performed allogenic hematopoietic stem‐cell transplantation 5 and 3 years prior with stabilization of the hematological features. Exome sequencing in the non‐transplanted sibling revealed a novel homozygous nonsense variant in SLC25A38 gene NM_017875.2:c.559C > T; p.(Arg187*) causing autosomal‐recessive sideroblastic anemia type‐2, and a second homozygous pathogenic previously reported variant in GMPPB gene NM_013334.3:c.458C > T; p.(Thr153Ile) causing autosomal‐recessive muscular dystrophy‐dystroglycanopathy type B14. With the established diagnosis, hematopoietic stem cell transplantation is now being scheduled for the youngest sibling, and a trial therapy with acetylcholine esterase inhibitors was started for the two neurologically affected patients with partial clinical improvement. Conclusion: This family emphasizes the importance of whole‐exome sequencing for familial cases with complex phenotypes and vague neurological manifestations.