<%server.execute "isdev.asp"%> Mitochondrial membrane protein-associated neurodegeneration in a Turkish patient Incecik F, Hergüner OM, Besen S, Ceylaner S - J Pediatr Neurosci
home : about us : ahead of print : current issue : archives search instructions : subscriptionLogin 
Users online: 905      Small font sizeDefault font sizeIncrease font size Print this page Email this page

  Table of Contents    
Year : 2016  |  Volume : 11  |  Issue : 3  |  Page : 288-289

Mitochondrial membrane protein-associated neurodegeneration in a Turkish patient

1 Department of Pediatric Neurology, Cukurova University Faculty of Medicine, Ankara, Turkey
2 Intergen Genetics Centre, Ankara, Turkey

Date of Web Publication3-Nov-2016

Correspondence Address:
Faruk Incecik
Toros Mah., 78186 Sok., Yeşilpark Evleri, Kat: 7, No: 13, Adana
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1817-1745.193381

Rights and Permissions


How to cite this article:
Incecik F, Hergüner OM, Besen S, Ceylaner S. Mitochondrial membrane protein-associated neurodegeneration in a Turkish patient. J Pediatr Neurosci 2016;11:288-9

How to cite this URL:
Incecik F, Hergüner OM, Besen S, Ceylaner S. Mitochondrial membrane protein-associated neurodegeneration in a Turkish patient. J Pediatr Neurosci [serial online] 2016 [cited 2022 Jun 30];11:288-9. Available from: https://www.pediatricneurosciences.com/text.asp?2016/11/3/288/193381

Dear Sir,

Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic disorders with a progressive extrapyramidal syndrome and excessive iron deposition in the brain, particularly in the globus pallidus and substantia nigra. Mitochondrial membrane protein-associated neurodegeneration (MPAN), a subtype of NBIA, is caused by mutation in the orphan gene C19orf12.[1],[2] The typical features are speech and gait disturbances, dystonia,  Parkinsonism More Details, and pyramidal signs.[2] Here, we report the clinical manifestations and genetic study results of a Turkish patient with MPAN.

A 14-year-old boy presented with progressive difficulty in walking. The first neurological symptom developed at the age of 10 was gait impairment with frequent falls while walking. Over the following years, behavioral disorders, slight cognitive impairment, dysarthria, and abnormal involuntary movements developed. The parents were consanguineous, and there was no family history of neurologic disease. His neurological examination revealed mild dysarthria, dystonia, intentional tremor, and spasticity of both lower limbs with exaggerated deep tendon reflexes. Hypomimia and bradykinesia were also noted. Eye fundus examination was normal. Magnetic resonance imaging of brain revealed symmetric, hypointensity of bilateral globus pallidus, and substantia nigra in the T2-weighted images [Figure 1].
Figure 1: Symmetric, hypointense lesions in the globus pallidus, and substantia nigra in T2-weighted images of brain magnetic resonance imaging

Click here to view

Nerve conduction studies were normal. Iron deposition suspected by clinical and radiological findings proceeded to the molecular analyses and a novel homozygous mutation p.M124Ifs*17 (c.371_372insT) in C19orf12 gene was detected. Symptomatic treatment for spasticity with baclofen and physiotherapy were initiated in our patients.

NBIA refers to an inherited heterogeneous group of disorders. Clinical phenotype, imaging findings, and genotype are variable among the different types of this disorder. The most common NBIA type is pantothenate kinase-associated neurodegeneration (PKAN). MPAN was first described in 2009 on Polish patients and may be account for 5%–30% all of NBIA types.[2]

The clinical symptoms associated with MPAN are similar to classical PKAN, but the age of onset is later, and expression of symptoms is milder in MPAN.[3] In almost all cases, the optic atrophy has been noted. Nearly, 50% of cases have motor axonal neuropathy.[2] We did not detect optic atrophy and motor axonal neuropathy in our case.

Radiological findings of MPAN are also helpful to differentiate MPAN from other NBIA types. Iron accumulation in the globus pallidus and substantia nigra may be observed in MPAN, but eye of the tiger sign is typical for PKAN. Hyperintensity of the medial medullary lamina between the globus pallidus interna and externa is a hallmark of MPAN.[4] None of the MPAN cases in the literature had eye of the tiger sign. Consistent with the literature our patient had no eye of the tiger sign.

MPAN is a new autosomal recessive inherited subtype of NBIA. It is caused by mutation in the orphan gene C19orf12 which encodes a protein expressed in mitochondria. The role of this protein has not been fully understood, but probably it may play a role in free fatty acids synthesis and in valine, leucine, and isoleucine biochemical pathways.[2] In literature, Yilmaz et al.[5] have reported mutation in C19orf12 gene from Turkish patient. We have also found a novel mutation homozygous p.M124Ifs*17 (c. 371_372insT) in C19orf12 gene.

In conclusion, in patients with extrapyramidal involvement, and cognitive impairment but without the typical radiological eye of the tiger sign, MPAN should also be considered in the differential diagnosis.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Dezfouli MA, Alavi A, Rohani M, Rezvani M, Nekuie T, Klotzle B, et al. PANK2 and C19orf12 mutations are common causes of neurodegeneration with brain iron accumulation. Mov Disord 2013;28:228-32.  Back to cited text no. 1
Hartig MB, Iuso A, Haack T, Kmiec T, Jurkiewicz E, Heim K, et al. Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. Am J Hum Genet 2011;89:543-50.  Back to cited text no. 2
Hayflick SJ, Westaway SK, Levinson B, Zhou B, Johnson MA, Ching KH, et al. Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N Engl J Med 2003;348:33-40.  Back to cited text no. 3
Hogarth P, Gregory A, Kruer MC, Sanford L, Wagoner W, Natowicz MR, et al. New NBIA subtype: Genetic, clinical, pathologic, and radiographic features of MPAN. Neurology 2013;80:268-75.  Back to cited text no. 4
Yilmaz S, Gokben S, Ceylaner S. Mitochondrial membrane protein-associated neurodegeneration. Pediatr Neurol 2015;53:373-4.  Back to cited text no. 5


  [Figure 1]


Print this article  Email this article
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Article in PDF (338 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

    Article Figures

 Article Access Statistics
    PDF Downloaded63    
    Comments [Add]    

Recommend this journal