A single large-scale deletion of mtDNA in a child with recurrent encephalopathy and tubulopathy

Abstract 

A 26-month-old child presented with an unusual combination of growth retardation, renal proximal tubulopathy, hypoparathyroidism, and episodic encephalopathy with fever and lethargy. Muscle biopsy revealed defects of mitochondrial respiratory chain enzyme complexes I, III, and IV, but no ragged-red fibers or cytochrome c oxidase deficient fibers. Analysis of muscle mitochondrial DNA (mtDNA) showed a heteroplasmic 7663base pair (bp) single deletion with a perfect 10bp direct sequence repeat at the boundaries. At age 3years and 9months, the child developed sepsis and acute deterioration of her encephalopathy leading to death. This case expands the phenotypic diversity of mitochondrial disorders in pediatric patients and reinforces the importance of biochemical analyses of muscle biopsies in patients suspected of having a mitochondrial disorder.

Keywords: Mitochondrial DNA deletion, Tubulopathy, Hypoparathyroidism, Encephalopathy, Leigh syndrome