Is it ADEM, POLG, or both?
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.


METHODS
Case report.


METHODS
Tertiary referral center.


METHODS
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.
Harris
Mandy O
MO
Department of Neurology, Division of Pediatric Neurology, Indiana University School of Medicine, 575 West Dr, Indianapolis, IN 46202, USA.
Walsh
Laurence E
LE
Hattab
Eyas M
EM
Golomb
Meredith R
MR
D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D020278:Demyelinating Autoimmune Diseases, CNS / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003937:Diagnosis, Differential; D004673:Encephalomyelitis, Acute Disseminated / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D017809:Fatal Outcome; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D009154:Mutation / Q000235:genetics*; D004676:Myelin Basic Protein / Q000134:cerebrospinal fluid; D043025:Oligoclonal Bands / Q000134:cerebrospinal fluid; D017211:Treatment Failure
D005819:Genetic Markers; D004676:Myelin Basic Protein; D043025:Oligoclonal Bands; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; D008775:Methylprednisolone