NBIA

Neurodegeneration with Brain Iron Accumulation (NBIA) is a collective term for a group of disorders marked by extrapyramidal symptoms and abnormal iron deposition in the deep basal ganglia. More than 10 genes are associated with NBIA, among which Mitochondrial Protein-Associated Neurodegeneration (MPAN) accounts for 10% of NBIA cases.

MPAN is fundamentally caused by pathogenic mutations in the C19orf12 gene, which encodes a mitochondrial membrane protein of largely unknown function. The C19orf12 protein is localized to the membrane of mitochondria, the cellular energy-producing centers, and researchers suggest it plays a role in lipid homeostasis, though its precise molecular function remains elusive. The disease demonstrates genetic heterogeneity in its inheritance patterns, with both autosomal recessive and autosomal dominant forms documented in the literature

Clinical findings

MPAN typically manifests during childhood or early adolescence, though cases with onset as late as the fourth decade of life have been documented. The clinical presentation of MPAN is characterized by a progressive constellation of movement disorders, cognitive decline, and neuropsychiatric abnormalities that distinguish it from other NBIA subtypes. The disease follows a relentlessly progressive course, with symptoms gradually worsening over time and ultimately proving uniformly fatal.