When a neurologist encounters a patient with a form of NBIA, it's often their first patient with NBIA.
“For most neurologists, the lineation of the different forms of neurodegeneration of brain iron accumulation (NBIA) has occurred since their training,” says Susan Hayflick, MD, professor of Molecular and Medical Genetics, Pediatrics, and Neurology, Oregon Health & Science University, Portland. “It’s just been in the last five to six years that we have sorted out the different forms of NBIA.”
Hayflick notes that although readily ascertained with brain MRI, NBIA is really a group of rare disorders. When a neurologist encounters a patient with one of these, it’s often the first patient they’ve ever had with NBIA. “The MRI sort of stimulates thinking about this group of disorders. You can go pretty far down the path of smart testing if you know what features on the MRI to pay attention to. The MRI can really guide that, and the history can really guide the testing, so you can save the patient and family both time and money by not going down the wrong testing pathway,” she says.
The problem is that the symptoms aren’t easy to recognize—“they’re all over the map,” notes Hayflick—and so usually when an MRI is performed for another reason, the signs are there to suggest iron in the brain.
The two main types of NBIA are Pantothenate Kinase-Associated Neurodegeneration (PKAN) and dystonia-Parkinsonism, which Hayflick says is a pretty common diagnosis, adding that many things can cause dystonia-Parkinsonism, including some of the NBIA genes. She also notes that the genetic causes of the various NBIA disorders are what differentiate them from one another.
With so many different causes, the diagnosis, management, and therapy of patients with NBIA varies quite a lot, with MRI and genetic testing leading the way toward a diagnosis and management and treatment mostly focused on symptoms. However, Hayflick points to clinical trials, for PKAN in particular, in which new medications are being tested to chelate iron. Other trials are in works for medications based on the understanding of the disease mechanisms—“A rational therapeutics approach,” she says.
“Like for many neurogenetic disorders, the NBIA are somewhat complex, but if you have a basic understanding of genetics and the power of and limitations of genetic testing, you can use it to enable you to get to a diagnosis quickly,” Hayflick concludes. “I actually think this group of disorders is a good paradigm for understanding how genetics gets us to ideas for rational therapies.”