Afagh Alavi - Genetics research center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
Reza Hajati-Kenarsari - Genetics research center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
Atefeh Davarzani - Genetics research center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
Mohammad Rohani - Department of Neurology, Iran University of Medical Sciences, Hazrat Rasool Hospital, Tehran, Iran

Background and Objective: Mitochondrial Membrane Protein Associated Neurodegeneration (MPAN) is an ultra-rare disease and a subtype of Neurodegeneration with Brain Iron Accumulation (NBIA) disorders caused by mutations in C19orf12 and characterized by abnormal iron deposition in the substantial nigra (SN) of the brain. Here, we present clinical findings and results of genetic analysis of an Iranian MPAN case with atypical pattern of brain iron deposition.Patient Report: Our case was a 38-year-old female with neuropsychiatric symptoms, dysarthria, imbalance and gait disturbance, tremor and spasticity of limbs and urinary and bowel incontinency. There was neither optic atrophy nor retinopathy. Brain MRI showed low signal intensity in the caudate, putamen, and substantial nigra bilaterally. Because of extensive and atypical pattern of brain iron accumulation in this case, we performed whole exome sequencing which revealed a homozygous mutation; c.C32T;p.Thr11Met in C19orf12 suggesting the diagnosis of MPAN.Conclusion: The second most common mutation in C19orf12 is p.Thr11Met and the mean age at onset of MPAN cases carried this mutation is 24.9 years. The mutation is associated with later disease onset compared to the other mutations. In all of these cases, brain MRI imaging was compatible with childhood onset cases of MPAN. Interestingly, our case presented rapid course and adult onset of the disease but the MRI was different and extensive iron deposition detected in SN, globus pallidus, caudate, putamen and periventricular area. It is suggested other genetic or environment factors may affect pattern of iron accumulation in the brain.

Mitochondrial Membrane Protein Associated Neurodegeneration, MPAN, Brain iron accumulation, Caudate, Globus pallidus, Optic atrophy, Putamen, Substantia nigra