Sideroblastic anemia associated with multisystem mitochondrial disorders
- PMID: 30588737
- DOI: 10.1002/pbc.27591
Sideroblastic anemia associated with multisystem mitochondrial disorders
Abstract
Background: Sideroblastic anemia represents a heterogeneous group of inherited or acquired diseases with disrupted erythroblast iron utilization, ineffective erythropoiesis, and variable systemic iron overload. In a cohort of 421 patients with multisystem mitochondrial diseases, refractory anemia was found in 8 children.
Results: Five children had sideroblastic anemia with increased numbers of ring sideroblasts >15%. Two of the children had a fatal course of MLASA1 syndrome (mitochondrial myopathy, lactic acidosis, and sideroblastic anemia [SA]) due to a homozygous, 6-kb deletion in the PUS1 gene, part of the six-member family of pseudouridine synthases (pseudouridylases). Large homozygous deletions represent a novel cause of presumed PUS1-loss-of-function phenotype. The other three children with SA had Pearson syndrome (PS) due to mtDNA deletions of 4 to 8 kb; two of these children showed early onset of PS and died due to repeated sepsis; the other child had later onset of PS and survived as the hematological parameters normalized and the disease transitioned to Kearns-Sayre syndrome. In addition, anemia without ring sideroblasts was found in three other patients with mitochondrial disorders, including two children with later onset of PS and one child with failure to thrive, microcephaly, developmental delay, hypertrophic cardiomyopathy, and renal tubular acidosis due to the heterozygous mutations c.610A>G (p.Asn204Asp) and c.674C>T (p.Pro225Leu) in the COX10 gene encoding the cytochrome c oxidase assembly factor.
Conclusions: Sideroblastic anemia was found in fewer than 1.2% of patients with multisystem mitochondrial disease, and it was usually associated with an unfavorable prognosis.
Keywords: MLASA; Pearson syndrome; mitochondrial disorders; mtDNA; ring sideroblasts; sideroblastic anemia.
© 2018 Wiley Periodicals, Inc.
Comment in
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Comment on: Sideroblastic anemia associated with multisystem mitochondrial disorders: The phenotypic spectrum of PUS1 and COX10 variants and mtDNA deletions needs to be prospectively assessed.Pediatr Blood Cancer. 2019 Nov;66(11):e27945. doi: 10.1002/pbc.27945. Epub 2019 Aug 8. Pediatr Blood Cancer. 2019. PMID: 31393068 No abstract available.
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Reply to Comment on: Sideroblastic anemia associated with multisystem mitochondrial disorders.Pediatr Blood Cancer. 2019 Dec;66(12):e28007. doi: 10.1002/pbc.28007. Epub 2019 Sep 18. Pediatr Blood Cancer. 2019. PMID: 31535449 No abstract available.
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