A novel C19ORF12 mutation in two MPAN sisters treated with deferiprone

Abstract

Abstract Background Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare and devastating disease caused by pathogenic mutations in C19orf12 gene. MPAN is characterized by pathological iron accumulation in the brain and fewer than 100 cases of MPAN have been described. Although the diagnosis of MPAN has achieved a great breakthrough with the application of the whole exome gene sequencing technology, the therapeutic effect of iron chelation therapy in MPAN remains controversial. Case presentation We reported that two sisters from the same family diagnosed with MPAN had dramatically different responses to deferiprone (DFP) treatment. The diagnosis of MPAN were established based on typical clinical manifestations, physical examination, brain magnetic resonance imaging (MRI), cerebrospinal fluid analysis (CSF) and gene sequencing results. The clinical presentations of the two sisters with MPAN due to novel gene locus mutations were similar to those previously reported. There is no other difference in basic information except that the proband had a later onset age and fertility history. Both the proband and his second sister were treated with deferiprone (DFP), but they had dramatically different responses to the treatment. The proband’s condition deteriorated sharply after treatment with DFP including psychiatric symptoms and movement disorders. However, the second sister of the proband became relatively stable after receiving the DFP treatment. After four years of follow-up, the patient still denies any new symptoms of neurological deficits. Conclusion The findings of this study enriched the MPAN gene database and indicated that DFP might ameliorate symptom progression in patients without severe autonomic neuropsychiatric impairment at the early stage of the disease.

Keywords

• C19orf12
• Mitochondrial membrane protein-associated neurodegeneration
• MPAN
• NBIA
• Deferiprone
• DFP