We describe here a previously unknown, dominantly inherited, late-onset basal ganglia disease, variably presenting with extrapyramidal features similar to those of Huntington's disease (HD) or parkinsonism. We mapped the disorder, by linkage analysis, to 19q13.3, which contains the gene for ferritin light polypeptide (FTL). We found an adenine insertion at position 460-461 that is predicted to alter carboxy-terminal residues of the gene product. Brain histochemistry disclosed abnormal aggregates of ferritin and iron. Low serum ferritin levels also characterized patients. Ferritin, the main iron storage protein, is composed of 24 subunits of two types (heavy, H and light, L) which form a soluble, hollow sphere. Brain iron deposition increases normally with age, especially in the basal ganglia, and is a suspected causative factor in several neurodegenerative diseases in which it correlates with visible pathology, possibly by its involvement in toxic free-radical reactions. We found the same mutation in five apparently unrelated subjects with similar extrapyramidal symptoms. An abnormality in ferritin strongly indicates a primary function for iron in the pathogenesis of this new disease, for which we propose the name 'neuroferritinopathy'.

Face processing and facial expression recognition were investigated in the earliest stages of Huntington's disease, by studying 40 people who presented for genetic testing. Twenty-three of these 'at risk' individuals turned out not to carry the gene for Huntington's disease (the AR- group). Seventeen were found to be gene carriers (the AR+ group); 15 from genetic testing, and two who showed signs of early stages of Huntington's disease. A number of standard tasks were used to provide background information, including recognition memory for words, picture naming, verbal fluency, and figure copying; none revealed significant differences between the AR+ and AR- groups. Face processing abilities were investigated using tests of identification of familiar (famous) faces, unfamiliar face matching, recognition memory for faces, and recognition of facial expressions of emotion. No statistically significant differences between the AR+ and AR- groups were found for any of these tests, but the AR+ group showed a borderline overall impairment in recognizing facial expressions of emotion (0.05 < P < 0.1). When recognition of each of the six basic emotions used was examined separately, only disgust was found to be significantly impaired. This highly selective deficit in the recognition of disgust was confirmed in the subgroup of 15 individuals shown by genetic testing to be Huntington's gene carriers; it was therefore found in people who were free from clinical symptoms and did not perform significantly more poorly than non-carriers on any of the background tests, on any of the other face processing tasks, and even for recognition of any other basic emotion. This points strongly to the importance of the basal ganglia in the emotion of disgust.

The abnormal assembly and accumulation of neurofilaments (NF) in the perikarya and proximal axons of motor neurones is a characteristic of ALS. Deletions in the KSP repeat region of the NF-H gene have previously been reported in seven patients with sporadic ALS. Here we report the identification of a novel 84 bp insertion in the NF-H gene. This leads to an extra four KSP repeat elements in a highly conserved repetitive region of the gene. Although neurofilament mutations are only associated with a very small proportion of ALS cases, this insertion provides further support of a role for neurofilaments in the pathogenesis of ALS.

We report a 70 year old German man presenting with a three year history of progressive numbness and painful tingling and burning paraesthesiae in his hands, feet, and lower legs, which had worsened during recent months. He also reported unsteadiness of gait, fatigue, night sweats, loss of appetite, and a weight loss of 12 kg within one year. He

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