Pearson syndrome: a multisystem mitochondrial disease with bone marrow failure

Abstract

Pearson syndrome (PS) is a rare fatal mitochondrial disorder caused by single large-scale mitochondrial DNA deletions (SLSMDs). Most patients present with anemia in infancy. Bone marrow cytology with vacuolization in erythroid and myeloid precursors and ring-sideroblasts guides to the correct diagnosis, which is established by detection of SLSMDs. Non hematological symptoms suggesting a mitochondrial disease are often lacking at initial presentation, thus PS is an important differential diagnosis in isolated hypogenerative anemia in infancy. Spontaneous resolution of anemia occurs in two-third of patients at the age of 1–3 years, while multisystem non-hematological complications such as failure to thrive, muscle hypotonia, exocrine pancreas insufficiency, renal tubulopathy and cardiac dysfunction develop during the clinical course. Some patients with PS experience a phenotypical change to Kearns-Sayre syndrome. In the absence of curative therapy, the prognosis of patients with PS is dismal. Most patients die of acute lactic acidosis and multi-organ failure in early childhood. There is a great need for the development of novel therapies to alter the natural history of patients with PS.

The metabolic basis of inherited neutropenias

“…When observed under the microscope, bone marrow shows vacuolization of haematopoietic precursors. 78,79 This syndrome is caused by single large-scale mitochondrial DNA (mtDNA) deletions. 79 Mitochondrial genome is essential to the biogenesis of the respiratory chain apparatus.…”

“…78,79 This syndrome is caused by single large-scale mitochondrial DNA (mtDNA) deletions. 79 Mitochondrial genome is essential to the biogenesis of the respiratory chain apparatus. mtDNA contains 37 genes that encode for 13 proteins, 22 tRNA and 2 rRNA.…”

Understanding the impact of pediatric single large‐scale mtDNA deletion syndromes on caregivers: Burdens and challenges

“…The prevalence of SLSMDS is estimated to be 1:1 000 000 and presents as a progressive multi‐system disease with a broad array of neural, hematologic, and gastrointestinal symptoms 1,2 . Advances in the hematologic management of Pearson syndrome have been successfully improving prognosis and longevity, 3 however the lifetime outlook remains bleak, with most patients requiring intensive symptom management and transfusions 1 . KSS is characterized by external ophthalmoplegia and pigmentary retinopathy and high cerebrospinal fluid (CSF) protein content, cardiac conduction block, and/or ataxia 1,2 .…”

“…Children can initially present with Pearson syndrome and then transition to KSS. Both phenotypes are associated with high morbidity, and neither has effective treatments or cures 2,3 …”

“…Both phenotypes are associated with high morbidity, and neither has effective treatments or cures. 2,3 Having a child with a complex, fatal illness is devastating for all members of the family and drastically impacts daily functioning. 4 Mothers, fathers, or other guardians (herein called "caregivers" for clarity) often experience great logistical and financial burden as they reduce their time at work to coordinate office visits, hospital stays, and travel accommodations.…”