It occurs either as a familial or a sporadic disorder and can have neurofibrillary tangles or Lewy bodies. The HSS gene is not sequenced yet and there is no clue as to normal role. It seems possible that it is a new type of mutation in prion gene that has gone unrecognized because it doesn't have a familiar CJD phenotype. Fatal Familial Insomnia also started off as a separate disorder until it was mapped and the prion gene defect determined. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course.
Histologic study reveals massive iron deposits in the basal ganglia.
Systemic and cerebrospinal fluid iron levels are normal, as are plasma levels of ferritin, transferrin and ceruloplasmin. Conversely, in disorders of systemic iron overload, such as haemochromatosis, brain iron is not increased, which suggests that fundamental differences exist between brain and systemic iron metabolism and transport. In normal brain, non-haem iron accumulates regionally and is highest in basal ganglia. Pathologic brain iron accumulation is seen in common disorders, including Parkinson's disease, Alzheimer's disease and Huntington disease. While this family was immensely powerful for mapping, the region demonstrating homozygosity in all affected members spans only 4 cM, requiring very close markers in order to detect linkage.