PP12.8 – 2541: A case of mitochondrial membrane protein associated neurodegeneration due to a novel mutation

Abstract

Objective Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a new described subgroup of neurodegeneration with brain iron accumulation caused by mutations in c19orf12 gene. The later age of onset, the presence of milder symptoms with slow progression, optic atrophy, motor axonal neuropathy, psychiatric disturbances, cognitive decline helps to distinguish MPAN from other types of NBIA. Methods A fourteen-year-old girl was referred for progressive vision loss, stepping on toes and frequent falls. Loss of vision was noticed at the age of seven and progressed rapidly in the last two years. The neurological examination of the case revealed bilateral optic atrophy, mild dysarthria, dystonia, intentional tremor and spastic gait. Brisk deep tendon reflexes in the lower extremities were noticed. The total IQ of the case, whose parents described mild cognitive decline was found as 50 at WISC-R test. Emotional lability was detected at psychiatric assesment. The cranial MRI of the case demonstrated T2-weighted hypointensity of bilateral globus pallidus and substantia nigra with bilateral central hyperintensity in the globus pallidus which were radiologically diagnostic for neurodegeneration with brain iron accumulation. The slow progression, presence of optic athropy, cognitive decline, emotional lability and absence of typical “eye of the tiger” sign were unlikely for the classical form of pantothenate kinase-associated neurodegeneration. The re-evaluation of the cranial MRI revealed hyperintense streaking of the medial medullary lamina between the globus pallidus externa and raised the suspicion of MPAN. Results c19orf12 gene sequencing analysis revealed a novel homozygote mutation, p.L121Q (c. 362T>A), was detected. Conclusion The clinical and radiological phenotype of the MPAN subtype is distinctive in some aspects. Considering the small size of the gene with only three exons, c19orf12 gene should be analysed in the patients who do not show the “eye of the tiger” sign and/or with optic atrophy, motor axonal neuropathy, psychiatric findings and cognitive decline.