Abstract
Neurodegeneration with brain iron accumulation (NBIA) is an umbrella term used to
clinically describe a group of neurologic conditions associated with high brain iron.
To date, there are 10 genetic subtypes described, which share several common clinical
features. Novel technologies such as improved magnetic resonance imaging techniques
and whole exome sequencing have provided new clinical and genetic insight into these
disorders, thereby improving clinical diagnosis for patients. Indeed, precise diagnosis
is now possible for approximately 60% of patients with NBIA. Despite these genetic
advances, little is known about the exact underlying disease pathways governing many
forms of NBIA. In fact, for most subtypes, the causative genes and affected proteins
are not directly related to iron homeostasis. Management for all subtypes remains
mainly supportive and based on a multidisciplinary approach, but there are promising
advances in the development of novel therapeutic strategies. Focusing mainly on the
newly described NBIA subtypes, we summarize the clinical phenotypes, genetic basis,
and postulated pathophysiological disease mechanisms, and propose an NBIA diagnostic
pathway to guide clinical testing and genetic councelling.
Keywords
neurodegeneration - mitochondrial membrane protein - β-Propeller protein - fatty acid
hydroxylase - phospholipase A2
