Broadening the phenotypic spectrum of Pearson syndrome: Five new cases and a review of the literature

Am J Med Genet A. 2020 Feb;182(2):365-373. doi: 10.1002/ajmg.a.61433. Epub 2019 Dec 11.


Pearson syndrome (PS) is a multisystem mitochondrial respiratory chain disorder typically characterized by sideroblastic anemia and exocrine pancreatic insufficiency. PS is caused by a single large-scale mitochondrial DNA (mtDNA) deletion. PS classically presents in the first year of life and may be fatal in infancy. Children who survive PS may progress to develop Kearns-Sayre syndrome later in life. The full phenotypic spectrum and prognosis of the condition continue to evolve. Here we report five new patients with PS with unique clinical presentations, including four patients with onset later than previously reported in the literature, and one patient with prenatal onset of symptoms. The timing and unique features of these presentations support an expanded phenotypic spectrum of single large-scale mtDNA deletion syndromes (SLSMDS) and reinforce the importance of including SLSMDS in the differential for children with complex multisystem presentations.

Keywords: Kearns-Sayre syndrome; Pearson syndrome; mitochondrial; single large-scale mitochondrial DNA deletion syndromes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anemia, Sideroblastic / genetics
  • Anemia, Sideroblastic / physiopathology
  • Child
  • Child, Preschool
  • Congenital Bone Marrow Failure Syndromes / genetics*
  • Congenital Bone Marrow Failure Syndromes / physiopathology
  • DNA, Mitochondrial / genetics*
  • Exocrine Pancreatic Insufficiency / genetics
  • Exocrine Pancreatic Insufficiency / physiopathology
  • Female
  • Gene Deletion
  • Humans
  • Infant
  • Kearns-Sayre Syndrome / genetics*
  • Kearns-Sayre Syndrome / physiopathology
  • Lipid Metabolism, Inborn Errors / genetics*
  • Lipid Metabolism, Inborn Errors / physiopathology
  • Male
  • Mitochondria / genetics
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / pathology
  • Mitochondrial Diseases / physiopathology
  • Muscular Diseases / genetics*
  • Muscular Diseases / physiopathology
  • Phenotype
  • Sequence Deletion / genetics


  • DNA, Mitochondrial

Supplementary concepts

  • VLCAD deficiency