Optic Atrophy in an Iron Storage Disorder Reducing Tissue Iron Load in a Child with MPAN Disease

Abstract

Case Study: We studied a case of a 13-year-old girl because of a progressive loss of vision due to an atrophy of her optic nerves. She had recently experienced increased difficulties at school, and minor gait abnormalities had been noted. On examination, her restricted cognitive abilities were not easily remarkable. Her gait was slightly abnormal and dystonic. Routine MRI studies of her brain showed areas of abnormally low T2 signal bilaterally in the substantia nigra and the globi pallidi, compatible with increased content of tissue iron. Molecular genetic investigations for causes of neurodegeneration with brain iron accumulation (NBIA) revealed two heterozygous mutations in the C19orf12 gene, known to cause mitochondrial membrane protein-associated neurodegeneration (MPAN), the phenotype spectrum of which includes optic atrophy. Although the pathomechanism of the disease is unknown, we speculated that an excess of iron in brain tissue is toxic and that reducing the excessive iron might be beneficial. Following schemes used for treatment of other NBIA, such as, phosphokinase-associated neurodegeneration, we started treatment with deferiprone, a chelating agent with the potential to remove tissue iron. The drug was tolerated well, but the dosage had sometimes to be reduced because of low-neutrophil counts. An improved MRI-based method of iron quantification in brain was used to sequentially follow the brain iron content under this therapy. Over a period of 2 years, the increased brain iron content slowly decreased in the substantia nigra, but it remained stable in the globi pallidi. Clinical findings remained stable with respect to cognition and vision, but running seemed to have become more difficult.