AIFM1 mutation presenting with fatal encephalomyopathy and mitochondrial disease in an infant

Cold Spring Harb Mol Case Stud. 2017 Mar;3(2):a001560. doi: 10.1101/mcs.a001560.


Apoptosis-inducing factor mitochondrion-associated 1 (AIFM1), encoded by the gene AIFM1, has roles in electron transport, apoptosis, ferredoxin metabolism, reactive oxygen species generation, and immune system regulation. Here we describe a patient with a novel AIFM1 variant presenting unusually early in life with mitochondrial disease, rapid deterioration, and death. Autopsy, at the age of 4 mo, revealed features of mitochondrial encephalopathy, myopathy, and involvement of peripheral nerves with axonal degeneration. In addition, there was microvesicular steatosis in the liver, thymic noninvolution, follicular bronchiolitis, and pulmonary arterial medial hypertrophy. This report adds to the clinical and pathological spectrum of disease related to AIFM1 mutations and provides insights into the role of AIFM1 in cellular function.

Keywords: brain atrophy; congenital lactic acidosis; elevated brain lactate level by MRS; infantile encephalopathy; lethal infantile mitochondrial myopathy; mitochondrial encephalopathy.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Inducing Factor / genetics*
  • Apoptosis Inducing Factor / metabolism
  • DNA, Mitochondrial / genetics
  • Electron Transport
  • Humans
  • Infant
  • Mitochondria / genetics
  • Mitochondrial Diseases / genetics
  • Mitochondrial Encephalomyopathies / genetics*
  • Muscle, Skeletal / metabolism
  • Muscular Diseases / metabolism
  • Mutation


  • AIFM1 protein, human
  • Apoptosis Inducing Factor
  • DNA, Mitochondrial