Compensatory amplification of mtDNA in a patient with a novel deletion/duplication and high mutant load

Abstract

A 41 year old female was diagnosed with chronic PEO (CPEO), ptosis, and pigmentary retinopathy at the age of 30 years. The patient was born to a 21 year old, G2P1 healthy mother after an uneventful pregnancy. She had a blood transfusion during the neonatal period for hyperbilirubinaemia, and had an otherwise unremarkable childhood. She also had transient, mild iron deficiency anaemia at approximately 9 years of age. She progressed through a normal puberty and had two normal pregnancies at 29 and 30 years of age. Following her first pregnancy, an ophthalmological examination revealed CPEO and retinopathy. No other diagnostic evaluation was suggested at that time. Eye muscle surgery was performed at 31 years of age, and the eyelids were surgically elevated bilaterally at 34 years. At 40 years of age, she developed left pelvic pain radiating to the lumbosacral spine region. Computed tomography scan of the pelvis and abdomen, magnetic resonance imaging of the lumbosacral spine, and colonoscopy were normal. She was treated with carbamazepine for neuralgia. The patient also began to experience palpitations and chest pain. An electrocardiogram showed very frequent premature ventricular contractions and occasional premature atrial contractions. An echocardiogram was normal except for mild mitral valve prolapse. A treadmill test showed comparatively limited exercise tolerance. She had mildly elevated serum lactate and lactate/pyruvate ratio, but plasma carnitine and urine organic acids were normal.