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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1997 Apr;62(4):319–328. doi: 10.1136/jnnp.62.4.319

The little imitator--porphyria: a neuropsychiatric disorder.

H L Crimlisk 1
PMCID: PMC1074085  PMID: 9120442

Abstract

Three common subtypes of porphyria give rise to neuropsychiatric disorders; acute intermittent porphyria, variegate porphyria, and coproporphyria. The second two also give rise to cutaneous symptoms. Neurological or psychiatric symptoms occur in most acute attacks, and may mimic many other disorders. The diagnosis may be missed because it is not even considered or because of technical problems, such as sample collection and storage, and interpretation of results. A negative screening test does not exclude the diagnosis. Porphyria may be overrepresented in psychiatric populations, but the lack of control groups makes this uncertain. The management of patients with porphyria and psychiatric symptoms causes considerable problems. Three cases are described to illustrate some of these issues. Advances in molecular biology permit identification of patients and latent carriers in the family. Care to avoid relapses and improved treatments have reduced the mortality.

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Selected References

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  1. ACKNER B., COOPER J. E., GRAY C. H., KELLY M. Acute porphyria: a neuropsychiatric and biochemical study. J Psychosom Res. 1962 Jan-Mar;6:1–24. doi: 10.1016/0022-3999(62)90019-3. [DOI] [PubMed] [Google Scholar]
  2. Badcock N. R., O'Reilly D. A., Zoanetti G. D., Robertson E. F., Parker C. J. Childhood porphyrias: implications and treatments. Clin Chem. 1993 Jun;39(6):1334–1340. [PubMed] [Google Scholar]
  3. Ben-Chetrit E., Putterman C. Clinical problem-solving. Still hazy after all these years. N Engl J Med. 1994 Oct 6;331(14):934–938. doi: 10.1056/NEJM199410063311409. [DOI] [PubMed] [Google Scholar]
  4. Black K. S., Mirsky P., Kalina P., Greenberg R. W., Drehobl K. E., Sapan M., Meikle E. Angiographic demonstration of reversible cerebral vasospasm in porphyric encephalopathy. AJNR Am J Neuroradiol. 1995 Sep;16(8):1650–1652. [PMC free article] [PubMed] [Google Scholar]
  5. Bonkovsky H. L. Advances in understanding and treating 'the little imitator,' acute porphyria. Gastroenterology. 1993 Aug;105(2):590–594. doi: 10.1016/0016-5085(93)90739-y. [DOI] [PubMed] [Google Scholar]
  6. Brodie M. J., Goldberg A. Acute hepatic porphyrias. Clin Haematol. 1980 Jun;9(2):253–272. [PubMed] [Google Scholar]
  7. Buttery J. E. Is the Watson-Schwartz screening method for porphobilinogen reliable? Clin Chem. 1995 Nov;41(11):1670–1671. [PubMed] [Google Scholar]
  8. Bylesjö I., Forsgren L., Lithner F., Boman K. Epidemiology and clinical characteristics of seizures in patients with acute intermittent porphyria. Epilepsia. 1996 Mar;37(3):230–235. doi: 10.1111/j.1528-1157.1996.tb00018.x. [DOI] [PubMed] [Google Scholar]
  9. Carter J. H. Updating acute intermittent porphyria: a case of self-mutilation. J Natl Med Assoc. 1977 Jan;69(1):51–52. [PMC free article] [PubMed] [Google Scholar]
  10. Case J. L. Palatography and myo-functional therapy. Int J Oral Myol. 1975 Apr;1(2):65–71. [PubMed] [Google Scholar]
  11. Coşkun T., Ozalp I., Koçak N., Yüce A., Caglar M., Berger R. Type I hereditary tyrosinaemia: presentation of 11 cases. J Inherit Metab Dis. 1991;14(5):765–770. doi: 10.1007/BF01799947. [DOI] [PubMed] [Google Scholar]
  12. Deacon A. C. Fecal porphyrin screening. Clin Chem. 1990 Jul;36(7):1383–1383. [PubMed] [Google Scholar]
  13. Doss M., Baumann H., Sixel F. Alcohol in acute porphyria. Lancet. 1982 Jun 5;1(8284):1307–1307. doi: 10.1016/s0140-6736(82)92874-4. [DOI] [PubMed] [Google Scholar]
  14. Downey D. C. Fatigue syndromes revisited: the possible role of porphyrins. Med Hypotheses. 1994 May;42(5):285–290. doi: 10.1016/0306-9877(94)90001-9. [DOI] [PubMed] [Google Scholar]
  15. Elder G. H. Molecular genetics of disorders of haem biosynthesis. J Clin Pathol. 1993 Nov;46(11):977–981. doi: 10.1136/jcp.46.11.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Flügel K. A., Druschky K. F. Electromyogram and nerve conduction in patients with acute intermittent porphyria. J Neurol. 1977 Mar 21;214(4):267–279. doi: 10.1007/BF00316572. [DOI] [PubMed] [Google Scholar]
  17. GOLDBERG A. Acute intermittent porphyria: a study of 50 cases. Q J Med. 1959 Apr;28(110):183–209. [PubMed] [Google Scholar]
  18. Grandchamp B., De Verneuil H., Beaumont C., Chretien S., Walter O., Nordmann Y. Tissue-specific expression of porphobilinogen deaminase. Two isoenzymes from a single gene. Eur J Biochem. 1987 Jan 2;162(1):105–110. doi: 10.1111/j.1432-1033.1987.tb10548.x. [DOI] [PubMed] [Google Scholar]
  19. Gregor A., Kostrzewska E., Tarczynska-Nosal S., Stachurska H. Coexistence of hereditary coproporphyria with acute intermittent porphyria. Ann Med. 1994 Apr;26(2):125–127. doi: 10.3109/07853899409147341. [DOI] [PubMed] [Google Scholar]
  20. Hardell L., Bengtsson N. O., Jonsson U., Eriksson S., Larsson L. G. Aetiological aspects on primary liver cancer with special regard to alcohol, organic solvents and acute intermittent porphyria--an epidemiological investigation. Br J Cancer. 1984 Sep;50(3):389–397. doi: 10.1038/bjc.1984.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Herrick A. L., McColl K. E., Wallace A. M., Moore M. R., Goldberg A. LHRH analogue treatment for the prevention of premenstrual attacks of acute porphyria. Q J Med. 1990 Apr;75(276):355–363. [PubMed] [Google Scholar]
  22. Hindmarsh J. T. Variable phenotypic expression of genotypic abnormalities in the porphyrias. Clin Chim Acta. 1993 Jul 30;217(1):29–38. doi: 10.1016/0009-8981(93)90235-v. [DOI] [PubMed] [Google Scholar]
  23. Jenkins T. The South African malady. Nat Genet. 1996 May;13(1):7–9. doi: 10.1038/ng0596-7. [DOI] [PubMed] [Google Scholar]
  24. KAELBLING R., CRAIG J. B., PASAMANICK B. Urinary porphobilinogen. Results of screening 2,500 psychiatric patients. Arch Gen Psychiatry. 1961 Nov;5:494–508. doi: 10.1001/archpsyc.1961.01710170072009. [DOI] [PubMed] [Google Scholar]
  25. Kauppinen R., Mustajoki P. Prognosis of acute porphyria: occurrence of acute attacks, precipitating factors, and associated diseases. Medicine (Baltimore) 1992 Jan;71(1):1–13. [PubMed] [Google Scholar]
  26. Kauppinen R., Mustajoki P. Prognosis of acute porphyria: occurrence of acute attacks, precipitating factors, and associated diseases. Medicine (Baltimore) 1992 Jan;71(1):1–13. [PubMed] [Google Scholar]
  27. King P. H., Bragdon A. C. MRI reveals multiple reversible cerebral lesions in an attack of acute intermittent porphyria. Neurology. 1991 Aug;41(8):1300–1302. doi: 10.1212/wnl.41.8.1300. [DOI] [PubMed] [Google Scholar]
  28. Laiwah A. C., Macphee G. J., Boyle P., Moore M. R., Goldberg A. Autonomic neuropathy in acute intermittent porphyria. J Neurol Neurosurg Psychiatry. 1985 Oct;48(10):1025–1030. doi: 10.1136/jnnp.48.10.1025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lim C. K., Peters T. J. Urine and faecal porphyrin profiles by reversed-phase high-performance liquid chromatography in the porphyrias. Clin Chim Acta. 1984 May 16;139(1):55–63. doi: 10.1016/0009-8981(84)90192-x. [DOI] [PubMed] [Google Scholar]
  30. Lindberg R. L., Porcher C., Grandchamp B., Ledermann B., Bürki K., Brandner S., Aguzzi A., Meyer U. A. Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria. Nat Genet. 1996 Feb;12(2):195–199. doi: 10.1038/ng0296-195. [DOI] [PubMed] [Google Scholar]
  31. Loftus L. S., Arnold W. N. Vincent van Gogh's illness: acute intermittent porphyria? BMJ. 1991 Dec 21;303(6817):1589–1591. doi: 10.1136/bmj.303.6817.1589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Logan G. M., Weimer M. K., Ellefson M., Pierach C. A., Bloomer J. R. Bile porphyrin analysis in the evaluation of variegate porphyria. N Engl J Med. 1991 May 16;324(20):1408–1411. doi: 10.1056/NEJM199105163242005. [DOI] [PubMed] [Google Scholar]
  33. Macalpine I., Hunter R. The "insanity" of King George 3d: a classic case of porphyria. Br Med J. 1966 Jan 8;1(5479):65–71. doi: 10.1136/bmj.1.5479.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Mandoki M. W., Sumner G. S. Psychiatric manifestations of hereditary coproporphyria in a child. J Nerv Ment Dis. 1994 Feb;182(2):117–118. doi: 10.1097/00005053-199402000-00012. [DOI] [PubMed] [Google Scholar]
  35. Massey E. W. Neuropsychiatric manifestations of porphyria. J Clin Psychiatry. 1980 Jun;41(6):208–213. [PubMed] [Google Scholar]
  36. McColl K. E., Thompson G. G., Moore M. R., Goldberg A., Church S. E., Qadiri M. R., Youngs G. R. Chester porphyria: biochemical studies of a new form of acute porphyria. Lancet. 1985 Oct 12;2(8459):796–799. doi: 10.1016/s0140-6736(85)90793-7. [DOI] [PubMed] [Google Scholar]
  37. McEneaney D., Hawkins S., Trimble E., Smye M. Porphyric neuropathy--a rare and often neglected differential diagnosis of Guillain-Barré syndrome. J Neurol Sci. 1993 Feb;114(2):231–232. doi: 10.1016/0022-510x(93)90304-h. [DOI] [PubMed] [Google Scholar]
  38. Meissner P. N., Dailey T. A., Hift R. J., Ziman M., Corrigall A. V., Roberts A. G., Meissner D. M., Kirsch R. E., Dailey H. A. A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria. Nat Genet. 1996 May;13(1):95–97. doi: 10.1038/ng0596-95. [DOI] [PubMed] [Google Scholar]
  39. Mustajoki P., Koskelo P. Hereditary hepatic porphyrias in Finland. Acta Med Scand. 1976;200(3):171–178. doi: 10.1111/j.0954-6820.1976.tb08216.x. [DOI] [PubMed] [Google Scholar]
  40. Mustajoki P., Nordmann Y. Early administration of heme arginate for acute porphyric attacks. Arch Intern Med. 1993 Sep 13;153(17):2004–2008. [PubMed] [Google Scholar]
  41. Mustajoki P., Tenhunen R. Variant of acute intermittent porphyria with normal erythrocyte uroporphyrinogen-I-synthase activity. Eur J Clin Invest. 1985 Oct;15(5):281–284. doi: 10.1111/j.1365-2362.1985.tb00185.x. [DOI] [PubMed] [Google Scholar]
  42. Patience D. A., Blackwood D. H., McColl K. E., Moore M. R. Acute intermittent porphyria and mental illness--a family study. Acta Psychiatr Scand. 1994 Apr;89(4):262–267. doi: 10.1111/j.1600-0447.1994.tb01511.x. [DOI] [PubMed] [Google Scholar]
  43. Peters H. A., Gocmen A., Cripps D. J., Bryan G. T., Dogramaci I. Epidemiology of hexachlorobenzene-induced porphyria in Turkey: clinical and laboratory follow-up after 25 years. Arch Neurol. 1982 Dec;39(12):744–749. doi: 10.1001/archneur.1982.00510240006002. [DOI] [PubMed] [Google Scholar]
  44. Philip A. T., Gerson B. Lead poisoning--Part I. Incidence, etiology, and toxicokinetics. Clin Lab Med. 1994 Jun;14(2):423–444. [PubMed] [Google Scholar]
  45. Phillips V. Queen Anne's "seventeen disappointments". Med J Aust. 1992 Mar 2;156(5):341–342. doi: 10.5694/j.1326-5377.1992.tb139793.x. [DOI] [PubMed] [Google Scholar]
  46. Pierach C. A., Weimer M. K., Cardinal R. A., Bossenmaier I. C., Bloomer J. R., Blommer J. R. Red blood cell porphobilinogen deaminase in the evaluation of acute intermittent porphyria. JAMA. 1987 Jan 2;257(1):60–61. [PubMed] [Google Scholar]
  47. Pinkham J. M., Southall D. P. Unusual case of suspected acute porphyria. Clin Chem. 1995 Feb;41(2):323–324. [PubMed] [Google Scholar]
  48. Ratnaike S., Blake D. The diagnosis and follow-up of porphyria. Pathology. 1995 Apr;27(2):142–153. doi: 10.1080/00313029500169762. [DOI] [PubMed] [Google Scholar]
  49. Reynolds N. C., Jr, Miska R. M. Safety of anticonvulsants in hepatic porphyrias. Neurology. 1981 Apr;31(4):480–484. doi: 10.1212/wnl.31.4.480. [DOI] [PubMed] [Google Scholar]
  50. Santosh P. J., Malhotra S. Varied psychiatric manifestations of acute intermittent porphyria. Biol Psychiatry. 1994 Dec 1;36(11):744–747. doi: 10.1016/0006-3223(94)90085-x. [DOI] [PubMed] [Google Scholar]
  51. Scane A. C., Wight J. P., Godwin-Austen R. B. Acute intermittent porphyria presenting as epilepsy. Br Med J (Clin Res Ed) 1986 Apr 5;292(6525):946–947. doi: 10.1136/bmj.292.6525.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Stein J. A., Tschudy D. P. Acute intermittent porphyria. A clinical and biochemical study of 46 patients. Medicine (Baltimore) 1970 Jan;49(1):1–16. [PubMed] [Google Scholar]
  53. Straka J. G., Rank J. M., Bloomer J. R. Porphyria and porphyrin metabolism. Annu Rev Med. 1990;41:457–469. doi: 10.1146/annurev.me.41.020190.002325. [DOI] [PubMed] [Google Scholar]
  54. Sweeney V. P., Pathak M. A., Asbury A. K. Acute intermittent porphyria. Increased ALA-synthetase activity during an acute attack. Brain. 1970;93(2):369–380. doi: 10.1093/brain/93.2.369. [DOI] [PubMed] [Google Scholar]
  55. Thunell S., Andersson C., Carlmark B., Floderus Y., Grönqvist S. O., Harper P., Henrichson A., Lindh U. Markers for vulnerability in acute porphyria. A hypothesis paper. Eur J Clin Chem Clin Biochem. 1995 Apr;33(4):179–194. doi: 10.1515/cclm.1995.33.4.179. [DOI] [PubMed] [Google Scholar]
  56. Thunell S., Floderus Y., Henrichson A., Moore M. R., Meissner P., Sinclair J. Alcoholic beverages in acute porphyria. J Stud Alcohol. 1992 May;53(3):272–276. doi: 10.15288/jsa.1992.53.272. [DOI] [PubMed] [Google Scholar]
  57. Tishler P. V., Woodward B., O'Connor J., Holbrook D. A., Seidman L. J., Hallett M., Knighton D. J. High prevalence of intermittent acute porphyria in a psychiatric patient population. Am J Psychiatry. 1985 Dec;142(12):1430–1436. doi: 10.1176/ajp.142.12.1430. [DOI] [PubMed] [Google Scholar]
  58. Vassallo M. J., Camilleri M., Sullivan S. N., Thomforde G. M. Effects of erythromycin on gut transit in pseudo-obstruction due to hereditary coproporphyria. J Clin Gastroenterol. 1992 Apr;14(3):255–259. doi: 10.1097/00004836-199204000-00013. [DOI] [PubMed] [Google Scholar]
  59. WALDENSTROM J. The porphyrias as inborn errors of metabolism. Am J Med. 1957 May;22(5):758–773. doi: 10.1016/0002-9343(57)90126-2. [DOI] [PubMed] [Google Scholar]
  60. WELLAND F. H., HELLMAN E. S., COLLINS A., HUNTER G. W., Jr, TSCHUDY D. P. FACTORS AFFECTING THE EXCRETION OF PORPHYRIN PRECURSORS BY PATIENTS WITH ACUTE INTERMITTENT PORPHYRIA. II. THE EFFECT OF ETHINYL ESTRADIOL. Metabolism. 1964 Mar;13:251–258. doi: 10.1016/0026-0495(64)90104-0. [DOI] [PubMed] [Google Scholar]
  61. Warren M. J., Jay M., Hunt D. M., Elder G. H., Röhl J. C. The maddening business of King George III and porphyria. Trends Biochem Sci. 1996 Jun;21(6):229–234. [PubMed] [Google Scholar]
  62. Whatley S. D., Roberts A. G., Elder G. H. De-novo mutation and sporadic presentation of acute intermittent porphyria. Lancet. 1995 Oct 14;346(8981):1007–1008. doi: 10.1016/s0140-6736(95)91692-x. [DOI] [PubMed] [Google Scholar]
  63. Yeung Laiwah A. C., Moore M. R., Goldberg A. Pathogenesis of acute porphyria. Q J Med. 1987 May;63(241):377–392. [PubMed] [Google Scholar]
  64. el-Shazly M. Acute intermittent porphyria: a family study. Br J Hosp Med. 1995 Feb 15;53(4):169–170. [PubMed] [Google Scholar]

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