"Two years ago, researchers at UCSF and OHSU located PANK2, the gene that when mutated causes HSS," said Susan Hayflick, M.D., associate professor of molecular and medical genetics in the OHSU School of Medicine. "The latest finding was a remarkable correlation that was made after studying patients who were PANK2-mutation positive. Magnetic resonance imaging (MRI) revealed the same brain disease patterns in each and every one of these patients."
The pattern, described as the "eye of the tiger sign" was located deep within a portion of the brain called the basal ganglia. The eye of the tiger pattern is thought to be caused by brain changes linked to an enzyme deficiency caused by the mutated PANK2 (pantothenate kinase) gene. The portion of the basal ganglia where the pattern was located is home to a number of other neurological disorders, including Parkinson's disease, Huntington's disease and Tourette's syndrome.
Much like Parkinson's disease, HSS is characterized by the accumulation of iron deposits in the brain. This results in gradual loss of muscle control, often leading to a vegetative state. Patients with HSS often also lose the ability to speak and chew food. HSS is an autosomal-recessive disorder, meaning both parents must contribute a mutated gene for their child to have the disease. Depending on the form of the disease, many patients die before age 20.
"Defining defects in PANK2 has led to the discovery of an unsuspected biochemical pathway in neurodegenerative diseases. We are now working to figure out why these defects lead to cell death and iron accumulation in this very specific area of the brain. One wonders whether defects in other enzymes in the pantothenate kinase pathway could also lead to neurodegenerative diseases for which we have no handle," said Jane Gitschier, Ph.D., UCSF professor of medicine and pediatrics.
To conduct this research, scientists from OHSU and UCSF studied 123 patients from 98 families. Some patients suffered from the classic form of the disease that appears early in life and progresses rapidly. The rest of the patients had the late-onset form of the disease that surfaces later in life and progresses at a slower rate.
In addition to the discovery of a new testing method for HSS patients, this research better defined the early- and late-onset forms of the disease. For instance, in patients with the late-onset form, severe stuttering, behavioral problems and Parkinsonian-like symptoms are often noted in the early stages of the disease. The research results may also lead to a new treatment. The enzyme deficiency linked to PANK2 mutations appears to be less severe in the late-onset form of the disease. At this point, researchers believe vitamin B-5 could help compensate for the deficiency, perhaps even in some early-onset cases. However, this is a hypothesis that requires further evaluation, researchers say.