A Boy With Muscle Weakness, Hypercarbia, and the Mitochondrial DNA A3243G Mutation

Russell P. Saneto, DO, PhD; Anthony Bouldin, MD


J Child Neurol. 2006;21(1):77-79. 

In This Article

Abstract and Introduction

The point mutation in the mitochondrial genome tRNALeu (A3243G) is associated with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS). We report a boy presenting with respiratory compromise and hypercarbia owing to severe muscle weakness. Historically, he demonstrated idiopathic growth hormone deficiency, retarded bone age, and exercise avoidance. Owing to severe respiratory compromise out of proportion to expected recovery, a metabolic work-up was performed. Muscle biopsy demonstrated abnormal mitochondria structure and heteroplasmic A3243G mutation. Idiopathic growth hormone deficiency and retarded bone age have not been previously reported in MELAS, and these findings delayed testing for mitochondrial disease. This case demonstrates that isolated muscle weakness in the context of other organ system abnormalities should make the investigator consider MELAS.

The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) is a well-defined mitochondrial encephalomyopathic syndrome.[1] This syndrome is genetically heterogeneous, with various point mutations in mitochondrial transfer ribonucleic acid and electron transport chain complexes.[2,3,4,5] The A3243G mutation accounts for 80% of the mutations identified in MELAS, with other abnormalities accounting for the remainder. Owing to threshold and heteroplasmy, the A3243G tRNALeu for leucine mutation can present with distinctive features not usually associated with classic MELAS.[1,6] We report the unique presentation of a child presenting with severe muscle weakness-induced hypercarbia, without the other cardinal features of MELAS, with the A3243G mutation. Retrospectively, this case suggests that retarded bone maturation and idiopathic growth hormone deficiency might be associated with the A3243G mutation.