Hallervorden-Spatz syndrome (HSS) and iron metabolism are reviewed in a scientific workshop sponsored by the NIH and HSS Association in Bethesda, MD. First reported in 1922, the syndrome is now classified in 3 clinical types: 1) early-onset childhood types, rapidly or slowly progressive; 2) late-onset, 10-18 years of age, slowly progressive; and 3) adult type, slowly progressive. Obligate characteristics are as follows: onset in the first two decades, progressive course, extrapyramidal signs (dystonia, rigidity, or choreoathetosis), MRI hypodensities corresponding with necrosis and iron deposits in basal ganglia, especially globus pallidus and substantia nigra, and the “eye-of-the-tiger” sign (higher signal intensity in centre and low signal on each side of globus pallidus).

Corrobarative signs (at least two) include: spasticity, intellectual deterioration, retinitis pigmentosa and/or optic atrophy, positive family history (autosomal recessive), and sea-blue histiocytes in bone marrow and/or abnormal cytosomes in circulating lymphocytes. Disorders to be excluded include: Wilson’s disease, neuronal ceroid lipofuscinosis, juvenile Huntington’s disease, GM1-galactosidase or hexosminidase A deficiencies. The differential diagnosis also includes the HARP syndrome, a possible phenotype of HSS (hypobetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration). The pathology. including iron metabolism and its accumulation in the basal ganglia, and symptomatic therapy are also discussed. [1]

COMMENT. The rare association of acanthocytosis and HSS has been reported by Swisher CN et al (1972), and the familial late infantile HSS has been described as a form of neuroacanthocytosis (Malandrini A et al, 1996). The above issue of Pediatric Neurology also includes reports on “Iron in the HSS,” (Koeppen AH, Dickson AC, 2001), “Iron overload, oxidative stress, and axonal dystrophy in brain disorders,” (Chiuch CC, 2001), “Systemic iron metabolism: a review and implications for brain iron metabolism,” (Rouault TA, 2001); “Iron and iron management proteins in neurobiology,” (Connor JR et al, 2001), and “Basal ganglia motor function in relation to Hallervorden-Spatz syndrome,” (Mink JW, 2001). It is postulated that dystonia and other extrapyramidal signs of HSS are attributed to degeneration of basal ganglia output neurons. (See Progress in Pediatric Neurology III, PNB Publ, 1997;pp560-565, for further references to Harp and HSS syndromes).