Mitochondrial DNA deletion in a child with megaloblastic anemia and recurrent encephalopathy.
A 3 1/2-year-old boy presented with megaloblastic anemia and recurrent episodes of severe lactic acidosis and coma. At age 4 years, he developed sepsis and died; postmortem examination failed to show any gross abnormality in any tissue. Biochemical analysis of muscle showed decreased activities for all respiratory chain enzymes except complex II. Muscle histochemistry revealed diffuse cytochrome c oxidase deficiency. Southern blot analysis of mitochondrial DNA from muscle, liver, and blood showed a heteroplasmic single mitochindrial DNA deletion of 2.4 kb, which removed the genes for cytochrome c oxidase I and II and the transfer ribonucleic acid genes for serine and aspartic acid. Single large-scale deletions in mitochondrial DNA have been associated with Pearson's syndrome, Kearns-Sayre syndrome, and progressive external ophthalmoplegia. This patient's presentation is unusual and suggests an overlap between Pearson's syndrome and Kearns-Sayre syndrome.
Akman
Cigdem Inan
CI
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Sue
Carolyn M
CM
Shanske
Sara
S
Tanji
Kurenai
K
Bonilla
Eduardo
E
Ojaimi
Joceline
J
Krishna
Sindu
S
Schubert
Romaine
R
DiMauro
Salvatore
S
D000140:Acidosis, Lactic / Q000235:genetics / Q000378:metabolism; D000749:Anemia, Megaloblastic / Q000150:complications / Q000235:genetics*; D015139:Blotting, Southern; D001928:Brain Diseases, Metabolic / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D002675:Child, Preschool; D003128:Coma / Q000235:genetics / Q000378:metabolism; D030401:Cytochrome-c Oxidase Deficiency / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D012008:Recurrence; D018805:Sepsis; D017384:Sequence Deletion
D004272:DNA, Mitochondrial