Clinical and imaging characteristics of late onset mitochondrial membrane protein-associated neurodegeneration (MPAN)

Ethan Gore; Brian S Appleby; Mark L Cohen; Suzanne D DeBrosse; James B Leverenz; Bruce L Miller; Sandra L Siedlak; Xiongwei Zhu; Alan J Lerner

doi:10.1080/13554794.2016.1247458

Clinical and imaging characteristics of late onset mitochondrial membrane protein-associated neurodegeneration (MPAN)

Neurocase. 2016 Oct;22(5):476-483. doi: 10.1080/13554794.2016.1247458. Epub 2016 Nov 1.

Authors

Ethan Gore¹, Brian S Appleby², Mark L Cohen³, Suzanne D DeBrosse⁴, James B Leverenz⁵, Bruce L Miller⁶, Sandra L Siedlak⁷, Xiongwei Zhu⁷, Alan J Lerner¹

Affiliations

¹ a Department of Neurology , University Hospitals Case Medical Center , Beachwood , OH , USA.
² b Departments of Neurology and Psychiatry , University Hospitals Case Medical Center , 3619 Park East Drive, Beachwood , OH , USA.
³ c Department of Pathology , University Hospitals Case Medical Center , Cleveland , OH , USA.
⁴ d Departments of Genetics and Genome Sciences, Pediatrics, and Neurology , University Hospitals Case Medical Center , Cleveland , OH , USA.
⁵ e Cleveland Clinic Lou Ruvo Center for Brain Health , Cleveland , OH , USA.
⁶ f Department of Neurology , University of California, San Francisco , San Francisco , CA , USA.
⁷ g Department of Pathology , Case Western Reserve University , Cleveland , OH , USA.

Abstract

Young onset dementias present significant diagnostic challenges. We present the case of a 35-year-old Kuwaiti man with social withdrawal, drowsiness, irritability, anxiety, aphasia, memory loss, hypereflexia, and Parkinsonism. Brain MRI showed bilateral symmetric gradient echo hypointensities in the globi pallidi and substantiae nigrae. Left cortical hypometabolism was seen on brain fluorodeoxyglucose positron emission tomography. A cortical brain biopsy revealed a high Lewy body burden. Genetic testing revealed a homozygous p.T11M mutation in the C19orf12 gene consistent with mitochondrial membrane protein-associated neurodegeneration. This is the oldest onset age of MPAN reported.

Keywords: Lewy body; Mitochondrial membrane protein-associatedneurodegeneration (MPAN); Parkinsonism; neurodegeneration with brain iron accumulation (NBIA); whole exome sequencing.

Publication types

Case Reports

MeSH terms

Adult
Family Health
Genetic Testing
Humans
Imaging, Three-Dimensional
Magnetic Resonance Imaging
Male
Mitochondrial Proteins / genetics*
Mutation / genetics*
Neurodegenerative Diseases / diagnostic imaging*
Neurodegenerative Diseases / genetics*
Positron-Emission Tomography

Substances

C19orf12 protein, human
Mitochondrial Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding