mtDNA Deletion in a Patient with Symptoms of Mitochondrial Cytopathy but without Ragged Red Fibers

We describe a heteroplasmic 4237-bp mitochondrial DNA (mtDNA) deletion in an 11-year-old girl who has suffered from progressive illness since birth. Her clinical features include global developmental delay with regression, brainstem dysfunction, lactic acidosis, and a history of pancytopenia and failure to thrive. The deletion spanned nt 9498 to nt 13734 and was flanked by a 12-bp direct repeat. Southern blot analysis also revealed an altered ApaI restriction site caused by a G → A nucleotide substitution at nt 1462 in the 12S rRNA gene. This homoplasmic nucleotide change was presumed to be a mtDNA nucleotide variant. No abnormalities of mitochondrial ultrastructure or distribution were observed, although mild deficiencies were noted for complexes IV, II + III, and I of the mitochondrial respiratory chain. The absence of ragged red fibers and COX-negative fibers in this patient shows that mtDNA deletions do not always result in these classical hallmarks of mitochondrial cytopathies.