Pearson syndrome in the neonatal period: two case reports and review of the literature.
ABSTRACT Pearson syndrome is a multiorgan mitochondrial cytopathy that results from defective oxidative phosphorylation owing to mitochondrial DNA deletions. Prognosis is severe and death occurs in infancy or early childhood. This article describes 2 cases with a severe neonatal onset of the disease. A review of the literature reveals the atypical presentation of the disease in the neonatal period, which is often overlooked and underdiagnosed.
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ABSTRACT: Beyond the disorders recognized as mitochondrial diseases, abnormalities in function and/or ultrastructure of mitochondria have been reported in several unrelated pathologies. These encompass ageing, malformations, and a number of genetic or acquired diseases, as diabetes and cardiologic, haematologic, organ-specific (e.g., eye or liver), neurologic and psychiatric, autoimmune, and dermatologic disorders. The mechanistic grounds for mitochondrial dysfunction (MDF) along with the occurrence of oxidative stress (OS) have been investigated within the pathogenesis of individual disorders or in groups of interrelated disorders. We attempt to review broad-ranging pathologies that involve mitochondrial-specific deficiencies or rely on cytosol-derived prooxidant states or on autoimmune-induced mitochondrial damage. The established knowledge in these subjects warrants studies aimed at elucidating several open questions that are highlighted in the present review. The relevance of OS and MDF in different pathologies may establish the grounds for chemoprevention trials aimed at compensating OS/MDF by means of antioxidants and mitochondrial nutrients.Oxidative Medicine and Cellular Longevity 05/2014; 2014:541230. DOI:10.1155/2014/541230 · 3.36 Impact Factor
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ABSTRACT: Pearson marrow pancreas syndrome (PS) is a multisystem disorder caused by mitochondrial DNA (mtDNA) deletions. Diamond Blackfan anemia (DBA) is a congenital hypoproliferative anemia in which mutations in ribosomal protein genes and GATA1 have been implicated. Both syndromes share several features including early-onset of severe anemia, variable non-hematologic manifestations, sporadic genetic occurrence, and occasional spontaneous hematologic improvement. Because of the overlapping features and relative rarity of PS, we hypothesized that some patients in whom the leading clinical diagnosis is DBA actually have PS. Here, we evaluated patient DNA samples submitted for DBA genetic studies, and found that eight (4.6%) of 173 genetically uncharacterized patients contained large mtDNA deletions. Only two (25%) of the patients had been diagnosed with PS on clinical grounds subsequent to sample submission. We conclude that PS can be overlooked, and that mtDNA deletion testing should be performed in the diagnostic evaluation of patients with congenital anemia.Blood 04/2014; 124(3). DOI:10.1182/blood-2014-01-545830 · 9.78 Impact Factor
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ABSTRACT: Mitochondria are the oxygen-consuming power plants of cells. They provide a critical milieu for the synthesis of many essential molecules and allow for highly efficient energy production through oxidative phosphorylation. The use of oxygen is, however, a double-edged sword that on the one hand supplies ATP for cellular survival, and on the other leads to the formation of damaging reactive oxygen species (ROS). Different quality control pathways maintain mitochondria function including mitochondrial DNA (mtDNA) replication and repair, fusion-fission dynamics, free radical scavenging, and mitophagy. Further, failure of these pathways may lead to human disease. We review these pathways and propose a strategy towards a treatment for these often untreatable disorders. Copyright © 2014. Published by Elsevier Ltd.Trends in Cell Biology 12/2014; DOI:10.1016/j.tcb.2014.11.002 · 12.31 Impact Factor