Journal of Pediatric Neurosciences
: 2016  |  Volume : 11  |  Issue : 3  |  Page : 288--289

Mitochondrial membrane protein-associated neurodegeneration in a Turkish patient

Faruk Incecik1, Ozlem M Hergüner1, Seyda Besen1, Serdar Ceylaner2,  
1 Department of Pediatric Neurology, Cukurova University Faculty of Medicine, Ankara, Turkey
2 Intergen Genetics Centre, Ankara, Turkey

Correspondence Address:
Faruk Incecik
Toros Mah., 78186 Sok., Yeşilpark Evleri, Kat: 7, No: 13, Adana

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;11:288-289

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 2021 May 15 ];11:288-289
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Full Text

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, 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}

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.

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2Hartig 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.
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