Is it ADEM, POLG, or both?

Arch Neurol. 2010 Apr;67(4):493-6. doi: 10.1001/archneurol.2010.36.


Objective: To describe a child with apparent brain biopsy-confirmed acute disseminated encephalomyelitis (ADEM) but genetic confirmation of compound heterozygosity for DNA mutations of the polymerase gamma (POLG) gene.

Design: Case report.

Setting: Tertiary referral center.

Patient: A 4-year-old boy presented with ataxia and encephalopathy.

Results: Magnetic resonance imaging demonstrated multiple focal areas of T2 prolongation. The patient's family refused steroid treatment. His symptoms improved then progressed. Magnetic resonance imaging findings also progressed. A cerebrospinal fluid specimen revealed myelin basic protein and oligoclonal bands. A brain biopsy specimen demonstrated demyelination, suggesting progression of ADEM. However, polymerase chain reaction amplification and sequencing revealed 2 heterozygous mutations of the POLG gene, suggesting mitochondrial disease. The patient died 9 months after his initial presentation.

Conclusions: This case raises interesting questions about whether ADEM triggered severe neurologic degeneration in a patient with mitochondrial disease, whether mitochondrial disease predisposed to a pathologic immune response, or whether mitochondrial disease can mimic an autoimmune disease. Mitochondrial disease-causing mutations may help explain the poor outcome in some cases of apparent autoimmune central nervous system disease.

Publication types

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

MeSH terms

  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Child, Preschool
  • DNA Mutational Analysis
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase / genetics*
  • Demyelinating Autoimmune Diseases, CNS / genetics
  • Demyelinating Autoimmune Diseases, CNS / immunology
  • Demyelinating Autoimmune Diseases, CNS / pathology
  • Diagnosis, Differential
  • Encephalomyelitis, Acute Disseminated / genetics*
  • Encephalomyelitis, Acute Disseminated / immunology
  • Encephalomyelitis, Acute Disseminated / pathology*
  • Fatal Outcome
  • Genetic Markers / genetics
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Methylprednisolone / therapeutic use
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / immunology
  • Mitochondrial Diseases / pathology*
  • Mutation / genetics*
  • Myelin Basic Protein / cerebrospinal fluid
  • Oligoclonal Bands / cerebrospinal fluid
  • Treatment Failure


  • Genetic Markers
  • Myelin Basic Protein
  • Oligoclonal Bands
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • POLG protein, human
  • Methylprednisolone