title: A novel mitochondrial DNA deletion in a patient with Kearns-Sayre syndrome: a late-onset of the fatal cardiac conduction deficit and cardiomyopathy accompanying long-term rGH treatment.
abstract: BACKGROUND
  Kearns-Sayre Syndrome (KSS) is a multisystem disorder caused by a dysfunction of the oxidative phosphorylation system within mitochondria. Mitochondrial DNA (mtDNA) rearrangements are a key molecular feature of this disease, which manifest a broad phenotypic spectrum.
  
  
  METHODS
  Here, we present a boy with KSS whose symptoms included cardiac conduction deficit, cardiomyopathy and growth hormone (GH) deficiency. The patient showed typical symptoms for KSS from early childhood (chronic progressive external ophthalmoplegia, retinopathy, short stature). Long-range PCR analysis disclosed a 7663-base pair heteroplasmic deletion in the mtDNA encompassing nucleotides 6340-14003. At 12 years of age, GH deficiency was recognized and recombinant growth hormone (rGH) therapy was started. At 15 years of age, a complete atrioventicular block was diagnosed and the patient received a pacemaker. During the following 6 months, progressive deterioration of the left ventricle was observed and an echocardiogram showed features of dilated cardiomyopathy. The rGH treatment was then discontinued at a final height of 163 cm. Unfortunately, due to multi-organ insufficiency and inflammation, the patient died at the age of 18 years.
  
  
  CONCLUSIONS
  The response to rGH therapy in the patient was very satisfactory. The large mtDNA deletion had no apparent impact on the response to rGH. Cardiac disturbances occurred as part of the syndrome and were not related to rGH therapy; however, the progression of the disease led to death.
authors: Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, 27/33 Szpitalna Street, 60-572, Poznan, Poland. m.moszynska@ump.edu.pl
authors: Monika
authors: M
authors: Obara-Moszynska
authors: Jaroslaw
authors: J
authors: Maceluch
authors: Waldemar
authors: W
authors: Bobkowski
authors: Artur
authors: A
authors: Baszko
authors: Oskar
authors: O
authors: Jaremba
authors: Maciej R
authors: MR
authors: Krawczynski
authors: Marek
authors: M
authors: Niedziela
mesh_terms: D000293:Adolescent; D054537:Atrioventricular Block / Q000175:diagnosis / Q000209:etiology; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000209:etiology; D004272:DNA, Mitochondrial; D017809:Fatal Outcome; D006130:Growth Disorders / Q000188:drug therapy / Q000209:etiology; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D011994:Recombinant Proteins; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial; D011994:Recombinant Proteins; D019382:Human Growth Hormone