Macrocytosis in Mitochondrial DNA Deletion Syndromes

Acta Haematol. 2023 Feb 10. doi: 10.1159/000529311. Online ahead of print.ABSTRACTLarge single mtDNA (mitochondrial DNA) deletion syndrome is a rare inborn error of metabolism with variable heteroplasmy levels and clinical phenotype among affected individuals. Chronic progressive external ophthalmoplegia (CPEO) is the most common phenotype in adults with this form of mitochondrial disease [1-2]. The common CPEO clinical manifestations are ptosis and ophthalmoplegia. More variable phenotypic manifestations of CPEO (CPEO plus) include involvement of the peripheral nervous system and myopathy. Here, we describe a 62-year-old female with CPEO and the major mitochondrial DNA deletion present at 40% heteroplasmy, who had a coexistent previously undescribed CPEO phenotypic feature of persistent unexplained macrocytosis without anemia. Building on this case, we reviewed other major mtDNA deletion cases seen in our Adult Metabolic Diseases Clinic (AMDC) at the University of British Columbia, Vancouver, Canada from 2016 to 2022. The major mtDNA deletion cases (n=26) were compared with mtDNA missense variants identified in the clinic over the same period who acted as the comparison group (n=16). Of these, the most frequent diagnosis was maternally inherited diabetes and deafness (MIDD) and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Ten out of 26 (38%) of mtDNA deletion patients had macrocytosis with elevated MCV (mean corpuscular volume), medi...
Source: Acta Haematologica - Category: Hematology Authors: Source Type: research