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

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

Ethan Gore  1 , Brian S Appleby  2 , Mark L Cohen  3 , Suzanne D DeBrosse  4 , James B Leverenz  5 , Bruce L Miller  6 , Sandra L Siedlak  7 , Xiongwei Zhu  7 , Alan J Lerner  1
Affiliations
Case Reports

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

Ethan Gore et al. Neurocase. 2016 Oct.

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.

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Conflict of interest statement

Disclosure statement

The authors have no financial or nonfinancial relationships to disclose.

Figures

Figure 1
Figure 1
Pedigree provided by the patient’s uncle demonstrating the consanguinity of the patient’s (proband’s) parents. The proband, a homozygote for the C19orf12 mutation, is depicted by a black square at the bottom. Heterozygotes are half shaded.
Figure 2
Figure 2
Top left: 3T MRI T1 coronal image with contrast showing bifrontal parenchymal volume loss, asymmetric parenchymal volume loss of the temporal lobes, and hypointensity of the globi pallidi. Top right: 3T MRI FLAIR axial image showing hypointensity of the globi pallidi and putamina, mild periventricular white matter hyperintensities, and left greater than right temporoparietal parenchymal volume loss. Bottom left: 3T MRI susceptibility weighted image (SWI) showing hypointensity of the globi pallidi, caudate heads, and putamina and relatively hyperintense streaking of the medullary laminae. Bottom right: 3T MRI SWI showing hypointensity of the substantiae nigrae as well as the globi pallidi, caudate heads, and putamina.
Figure 3
Figure 3
Top: FDG-PET axial image showing relative hypoperfusion of the left temporal, parietal, occipital, and insular frontal cortices. Bottom: FDG-PET coronal image showing relative hypoperfusion of the left frontal and temporal cortices.
Figure 4
Figure 4
Top left: Hematoxylin and eosin stain of cortex showing spherical neuronal intracytoplasmic inclusions resembling Lewy bodies in the top circle and similar extra-neuronal inclusions in the bottom circle. Top right: Hematoxylin and eosin stain of cortex with a higher magnification view of the extra-neuronal inclusions that resemble extra-neuronal Lewy bodies. Bottom left: Alpha synuclein immunohistochemistry staining of the intracytoplasmic inclusions. Bottom right: Ubiquitin-binding protein p62 immunohistochemistry staining of the intracytoplasmic inclusions.
Figure 5
Figure 5
CT axial image showing bilateral hyperdensities in the globi pallidi and pneumocephaly from a left frontal brain biopsy.
See this image and copyright information in PMC

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References

    1. Al-Semari A, Bohlega S. Autosomal-recessive syndrome with alopecia, hypogonadism, progressive extra-pyramidal disorder, white matter disease, sensory neural deafness, diabetes mellitus, and low IGF1. American Journal of Medical Genetics Part A. 2007;143a:149–160. doi: 10.1002/ajmg.a.31497. - DOI - PubMed
    1. Amaral LLF, Gaddikeri S, Chapman PR, Roy R, Gaddikeri RS, Marussi VH, Bag AK. Neurodegeneration with brain iron accumulation: Clinicoradiological approach to diagnosis. Journal of Neuroimaging. 2015;25:539–551. doi: 10.1111/jon.12195. - DOI - PubMed
    1. Aoki S, Okada Y, Nishimura K, Barkovich AJ, Kjos BO, Brasch RC, Norman D. Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T. Radiology. 1989;172:381–385. doi: 10.1148/radiology.172.2.2748819. - DOI - PubMed
    1. Aoun M, Tiranti V. Mitochondria: A crossroads for lipid metabolism defect in neurodegeneration with brain iron accumulation diseases. The International Journal of Biochemistry & Cell Biology. 2015;63:25–31. doi: 10.1016/j.biocel.2015.01.018. - DOI - PubMed
    1. Colombelli C, Aoun M, Tiranti V. Defective lipid metabolism in neurodegeneration with brain iron accumulation (NBIA) syndromes: Not only a matter of iron. Journal of Inherited Metabolic Disease. 2015;38:123–136. doi: 10.1007/s10545-014-9770-z. - DOI - PubMed

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