correspondence

Dystonia
To the Editor: The review of dystonia by Tarsy and Simon (Aug. 24 issue)1 contains misleading statements about dystonia 3 (also referred to as X-linked dystoniaparkinsonism [XDP] and lubag), which is an important differential diagnosis in people of Filipino descent who present with dystonia, parkinsonism, or both. Table 2 of the article by Tarsy and Simon incorrectly states that dystonia 3 is endemic in Panay, Philippines. Although the disorder originated through a founder effect on the Philippine island of Panay, it is not endemic there. Rather, XDP occurs in people of Filipino descent independently of their location. Several cases have been diagnosed in the United States, Canada, and Europe. The table also states that there is no known mutation in dystonia 3. In fact, there are several disease-specific sequence changes (DSCs) within the TAF1/DYT3 transcript system, including one in a transcribed exon (DSC3), that facilitate the unequivocal molecular diagnosis of dystonia 3.2 Ulrich Mller, M.D., Ph.D.
Institut fr Humangenetik D-35392 Giessen, Germany
1. Tarsy D, Simon DK. Dystonia. N Engl J Med 2006;355:818-29. 2. Nolte D, Niemann S, Mller U. Specific sequence changes in

known, whereas, in fact, mutations have been reported in the myofibrillogenesis regulator 1 (MR-1) gene in association with this disorder.2,3 In their original report, Lee and colleagues described 28 Filipino men with torsion dystonia that was thought to be X-linked, 23 of whom were from the island of Panay.4 A subsequent study confirmed that the prevalence of dystonia 3 in Panay was 13 times that in the general Philippine population. The prevalence in the province of Capiz (which is on the island of Panay) is about 1 case per 4500 men, which is 60 times that in the general population.5 Lee et al. state that the figures suggest that XDP is endemic in Panay, particularly in Capiz. We agree with these authors use of the term endemic, meaning a disease usually present or always present in a region or population. Its presence elsewhere does not contradict this designation. David K. Simon, M.D., Ph.D. Daniel Tarsy, M.D.
Beth Israel Deaconess Medical Center Boston, MA 02215 dtarsy@bidmc.harvard.edu
1. Nolte D, Niemann S, Mller U. Specific sequence changes in

multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism. Proc Natl Acad Sci U S A 2003;100:10347-52.

The authors reply: We thank Mller for pointing out that Table 2 incorrectly lists the mutations for dystonia 3 as unknown. The mutations in the TAF1/DYT3 multiple transcript system should have been listed.1 In the table, the mutation involved in dystonia 8 was also incorrectly listed as un-

multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism. Proc Natl Acad Sci U S A 2003;100:10347-52. 2. Rainier S, Thomas D, Tokarz D, et al. Myofibrillogenesis regulator 1 gene mutations cause paroxysmal dystonic choreoathetosis. Arch Neurol 2004;61:1025-9. 3. Lee HY, Xu Y, Huang Y, et al. The gene for paroxysmal nonkinesigenic dyskinesia encodes an enzyme in a stress response pathway. Hum Mol Genet 2004;13:3161-70. 4. Lee LV, Pascasio FM, Fuentes FD, Viterbo GH. Torsion dystonia in Panay, Philippines. Adv Neurol 1976;14:137-51. 5. Lee LV, Munoz EL, Tan KT, Reyes MT. Sex linked recessive dystonia parkinsonism of Panay, Philippines (XDP). Mol Pathol 2001;54:362-8.

The Severe Gout of Emperor Charles V

To the Editor: Ordi et al. (Aug. 3 issue)1 confirm that the Holy Roman Emperor Charles V suffered from what physicians had long suspected was severe tophaceous gout.2 Lead poisoning may also have contributed to the decline and fall of this emperor.3 Saturnine gout results from exposure to lead through the addition of lead sugar (acetate) to wine to sweeten it and from the leaching of lead from glazes on amphora or from pewter drinking vessels. Voracious consumption of wine (and lead) addled not only the Romans, but also the bibulous, podagrous English aristocrats of the 18th century,4 who were immortalized by Hogarths caricatures. Ordi and colleagues tell us that Charles V liked to drink large quantities of beer and wine and that he even ordered a specially designed fourhandled drinking mug. It would be fascinating to know the material from which his chalice was made. Even more interesting would be an analysis

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of the final phalanx of the emperors fifth finger further analyze the bone and soft tissues surfor lead content. rounding the tophi from Charles V and found no traces of lead. It would be interesting to know Richard T.L. Couper, F.R.A.C.P. whether the emperors specially designed mug or University of Adelaide Adelaide 5006, Australia other vessels contained lead, but we have no recrichard.couper@adelaide.edu.au ord of their current whereabouts. The negative re1. Ordi J, Alonso PL, de Zulueta J, et al. The severe gout of Holy sults of our recent analysis and the historical recRoman Emperor Charles V. N Engl J Med 2006;355:516-20. ords regarding the emperors gluttony suggest that 2. Boonen A, van der Linden SJ. Case number 33: about being a famous European and suffering from gout.... Ann Rheum Dis his condition was most likely related to his die2005;64:528. tary habits. 3. Nriagu JO. Saturnine gout among Roman aristocrats: did lead poisoning contribute to the fall of the Empire? N Engl J Med Pedro L. Fernndez, M.D. Pedro L. Alonso, M.D. 1983;308:660-3.
4. Ball GV. Two epidemics of gout. Bull Hist Med 1971;45:401-8.

Hospital Clnic dInvestigacions Biomdiques August Pi i Sunyer 08036 Barcelona, Spain

1. Boonen A, van der Linden SJ. Case number 33: about being a

The Authors Reply: Dr. Couper suggests the interesting possibility of lead poisoning as a cause of Emperor Charles Vs gout,1 a condition that has been reported to have afflicted other historic figures.2 Chronic lead poisoning impairs urate excretion, leading to hyperuricemia,3,4 and the composition of the crystals in the joints is similar to that of crystals caused by common gout. Nevertheless, we used scanning electron microscopy to

famous European and suffering from gout.... Ann Rheum Dis 2005;64:528. 2. Nriagu JO. Saturnine gout among Roman aristocrats: did lead poisoning contribute to the fall of the Empire? N Engl J Med 1983;308:660-3. 3. Lin JL, Huang PT. Body lead stores and urate excretion in men with chronic renal disease. J Rheumatol 1994;21:705-9. 4. Shadick NA, Kim R, Weiss S, Liang MH, Sparrow D, Hu H. Effect of low level lead exposure on hyperuricemia and gout among middle aged and elderly men: the Normative Aging Study. J Rheumatol 2000;27:1708-12.

Case 24-2006: A Woman with Hypotension after an Overdose of Amlodipine

To the Editor: In the Case Record presented in the August 10 issue,1 which describes the management of an overdose of amlodipine, Harris cites Kline et al.2 and states that data from studies in animals and humans support the administration of insulin while maintaining normal blood glucose levels (hyperinsulinemiaeuglycemia therapy) as first-line therapy in poisoning with calciumchannel blockers. Kline et al. reported the effects of this therapy in canines only and concluded that, as compared with glucagon, calcium chloride, or epinephrine, hyperinsulinemiaeuglycemia therapy prolonged survival. In humans, however, this therapy has been reported to be successful only in single cases and case series, and these reports have recommended that it be used as an adjunct to conventional therapy.3 Furthermore, the guidelines provided in Table 4 of the Case Record are mere proposals.3 In a review of the literature, Shepherd and Klein-Schwartz4 noted that there had been 13 published cases of hyperinsulinemia euglycemia therapy for overdoses of calciumchannel blockers in humans and that no data from clinical trials were available. We agree that on the basis of animal models and preliminary data, hyperinsulinemiaeuglycemia therapy appears to be a promising option in patients with life-threatening calcium-channel blocker overdose, but we think that it is premature to call this investigational and emerging therapy the first line of treatment until data from prospective clinical trials are available. Charu Aggarwal, M.B., M.P.H. Sameer Gupta, M.B., M.P.H.
State University of New York at Buffalo Buffalo, NY 14215 sgupta5@buffalo.edu
1. Case Records of the Massachusetts General Hospital (Case

24-2006). N Engl J Med 2006;355:602-11. 2. Kline JA, Leonova E, Raymond RM. Beneficial myocardial metabolic effects of insulin during verapamil toxicity in the anesthetized canine. Crit Care Med 1995;23:1251-63. 3. Boyer EW, Duic PA, Evans A. Hyperinsulinemia/euglycemia therapy for calcium channel blocker poisoning. Pediatr Emerg Care 2002;18:36-7. 4. Shepherd G, Klein-Schwartz W. High-dose insulin therapy for calcium-channel blocker overdose. Ann Pharmacother 2005; 39:923-30.

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