What is Hallervorden-Spatz syndrome

The most common, though now discouraged name for a rare, usually inherited movement disorder caused by an abnormal accumulation of iron in the basal ganglia and other parts of the brain that control movement, which destroys the cells. The syndrome is named after the two German researchers who first identified it in 1922 but the well-documented unethical actions of Dr. Hallervorden, and perhaps Dr. Spatz as well, during the Nazi era have led to popular efforts to rename the disorder. In medical circles today, it is more properly called neurodegeneration with brain iron accumulation type 1 (NBIA-1) or neuroaxonal dystrophy. Recent genetic discoveries have led many in the direction of considering this to be a syndrome (cluster of diseases with a nearly identical clinical picture) that can be split into more specific diseases, based upon the genetic defect. About 50 percent of patients with this syndrome have PKAN (pan-tothenate kinase associated neurodegeneration), caused by a defect of the gene PANK2, which causes a deficiency of the enzyme pantothenate kinase. NBIA-1 is considered a parkinsonism: That is, it affects the same parts of the brain in the same ways and its symptoms mimic those of Parkinson’s disease. Occasionally NBIA-1 occurs sporadically (as a random genetic defect that is not familial), though the usual form is autosomal recessive and can easily appear sporadic unless there are affected siblings: only one in four offspring of unaffected parents who both carry the defect will have the disease. There also are components of NBIA-1 that are similar to Alzheimer’s disease.

The Pathology of NBIA-1

Symptoms typically begin in childhood or early adolescence and progressively worsen over a period of about 10 years. They include bradykinesia (slowed movement), tremors (involuntary, repetitive movements), choreoathetosis (rhythmic, writing movements), dystonia (abnormal fixed postures), spasticity (abnormal tightening of the muscles), rigidity (continuous resistance of the muscles to relaxing), and gait disturbances (changes in the movements related to walking). cognitive dysfunction and dementia rapidly follow as these neuromuscular symptoms progress. Unlike Parkinson’s, NBIA-1 is fatal. anti-parkin-son’s medications, including levodopa, and drugs taken to treat huntington’s disease, another hereditary movement disorder, can provide symptom relief early in the course of the disease but are not very effective by mid and later stages.

Why NBIA-1 Interests Researchers in Parkinson’s Disease

NBIA-1 contains pathological components (symptoms and progression of the disease process) that are very similar to those of both Parkinson’s and Alzheimer’s, bolstering the belief that there is a connection between Parkinson’s and Alzheimer’s and possibly with other neurodegenerative conditions. The loss of dopaminergic neurons and other cellular structures (such as glial cells and myelinated fiber clusters) in NBIA-1 is so severe and so rapid that

FUNCTIONAL IMAGING STUDIES such as MAGNETIC RESONANCE imaging (MRI) show that rather than shrinking, as occurs with Parkinson’s, the substantia nigra and the striatum appear filled with holes. There are also pervasive lewy bodies with high alpha-synu-clein content throughout the basal ganglia, another hallmark of Parkinson’s disease (detectable only at autopsy). Neurofibrillary tangles containing tau, the hallmark of Alzheimer’s disease (also detectable only at autopsy), are present as well, reinforcing the perception many researchers have that there are pathological connections between Alzheimer’s and Parkinson’s.

In recent years scientists have isolated several gene mutations that appear responsible for NBIA-1 and suspect that there are others that act in concert to cause the development of the syndrome. These involve different genes than those isolated for either Alzheimer’s disease or Parkinson’s disease. Yet many of the mutations isolated among these diseases have in common that they have roles in enzyme-protein functions that are essential for cell activities. Disrupting these functions results in cell dysfunction and death. Figuring out how to correct or overcome the effect of the mutations could take researchers to the cure for these diseases. Because there has not yet been a known case of NBIA-1 in which there were not gene mutations, it appears that environmental factors may play little to no role in this syndrome (as in huntington’s disease). As most scientists believe that interactions among genetic and environmental factors cause the development of both Parkinson’s and Alzheimer’s, this aspect of NBIA-1 is particularly intriguing.