Skip to main content

Advertisement

SpringerLink
Log in

Neurological Manifestations of Acute Porphyrias

  • Neurology of Systemic Diseases (J. Biller, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Porphyrias constitute a group of rare metabolic disorders that result in a deficiency of the heme biosynthetic pathway and lead to the accumulation of metabolic intermediaries. Patients with porphyria can experience recurrent neurovisceral attacks which are characterized by neuropathic abdominal pain and acute gastrointestinal symptoms, including nausea, vomiting, and constipation. Depending on the type of porphyria, patients can present with cutaneous manifestations, such as severe skin photosensitivity, chronic hemolysis, or evidence of neurologic dysfunction, including alterations in consciousness, neurovascular involvement, seizures, transient sensor-motor symptoms, polyneuropathy, and behavioral abnormalities.

Recent Findings

More recently, cases of posterior reversible encephalopathy syndrome, cerebral vasoconstriction, and acute flaccid paralysis have also been described. While the exact pathogenic mechanisms linking the accumulation of abnormal heme biosynthetic intermediaries to neurologic manifestations have not been completely elucidated, it has been proposed that these manifestations are more common than previously thought and can result in permanent neurologic injury.

Summary

This article reviews the basic principles of heme synthesis as well as the pathogenic mechanism of disease, presentation, and treatment of acute hepatic porphyrias with emphasis on those with neurologic manifestations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Yasuda M, Chen B, Desnick RJ. Recent advances on porphyria genetics: inheritance, penetrance & molecular heterogeneity, including new modifying/causative genes. Mol Genet Metab. 2019;128:320–31.

    Article  CAS  Google Scholar 

  2. Puy H, Gouya L, Deybach J. Porphyrias. Lancet. 2010;375:924–37.

    Article  CAS  Google Scholar 

  3. Szlendak U, Bykowska K, Lipniacka A. Clinical, biochemical and molecular characteristics of the main types of porphyria. Adv Clin Exp Med. 2016;25:361–8.

    Article  Google Scholar 

  4. Phillips JD. Heme biosynthesis and the porphyrias. Mol Genet Metab. 2019;128:164–77 (• This publication provides a detailed description of the biochemistry of heme.).

    Article  CAS  Google Scholar 

  5. Pischik E, Kazakov V, Kauppinen R. Is screening for urinary porphobilinogen useful among patients with acute polyneuropathy or encephalopathy? J Neurol. 2008;255:974–9.

    Article  CAS  Google Scholar 

  6. Suh Y, Gandhi J, Seyam O, Jiang W, Joshi G, Smith NL, Ali KS. Neurological and neuropsychiatric manifestations of porphyria. Int J Neurosci. 2019;129:1226–33.

    Article  CAS  Google Scholar 

  7. Silveira DC, Bashir M, Daniel J, Lucena MH, Bonpietro F. Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome and lateralized periodic discharges plus fast activity on EEG. Epilepsy Behav Case Rep. 2016;6:58–60.

    Article  Google Scholar 

  8. Takata T, Kume K, Kokudo Y, Ikeda K, Kamada M, Touge T, Deguchi K, Masaki T. Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome, accompanied by prolonged vasoconstriction. Intern Med. 2017;56:713–7.

    Article  Google Scholar 

  9. Anderson R, Patel V, Sheikh-Bahaei N, Liu CSJ, Rajamohan AG, Shiroishi MS, Kim PE, Go JL, Lerner A, Acharya J. Posterior reversible encephalopathy syndrome (PRES): pathophysiology and neuro-imaging. Front Neurol. 2020;11:463.

    Article  Google Scholar 

  10. Zheng X, Liu X, Wang Y, Zhao R, Qu L, Pei H, Tuo M, Zhang Y, Song Y, Ji X, et al. Acute intermittent porphyria presenting with seizures and posterior reversible encephalopathy syndrome: two case reports and a literature review. Medicine (Baltimore). 2018;97: e11665.

    Article  Google Scholar 

  11. Zhao B, Wei Q, Wang Y, Chen Y, Shang H. Posterior reversible encephalopathy syndrome in acute intermittent porphyria. Pediatr Neurol. 2014;51:457–60.

    Article  Google Scholar 

  12. Rasheed F, Mehdi QS, Bhatti S, Khan MMA. Posterior reversible encephalopathy syndrome in a patient with variegate porphyria: a case report. Cureus . 2018;10.

  13. Hagemann G, Ugur T, Witte OW, Fitzek C. Recurrent posterior reversible encephalopathy syndrome (PRES). J Hum Hypertens. 2004;18:287–9.

    Article  CAS  Google Scholar 

  14. Pilato F, Distefano M, Calandrelli R. Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome: clinical and radiological considerations. Front Neurol. 2020;11:34.

    Article  Google Scholar 

  15. Mullin S, Platts A, Randhawa K, Watts P. Cerebral vasospasm and anterior circulation stroke secondary to an exacerbation of hereditary corproporphyria. Pract Neurol. 2012;12:384–7.

    Article  Google Scholar 

  16. Bastide L, Legros B, Rampal N, Gilmore EJ, Hirsch LJ, Gaspard N. Clinical correlates of periodic discharges and nonconvulsive seizures in posterior reversible encephalopathy syndrome (PRES). Neurocrit Care. 2018;29:481–90.

    Article  Google Scholar 

  17. Dawit S, Bhatt SK, Das DM, Pines AR, Shiue HJ, Goodman BP, Drazkowski JF, Sirven JI. Nonconvulsive status epilepticus secondary to acute porphyria crisis. Epilepsy Behav Case Rep. 2019;11:43–6.

    Article  Google Scholar 

  18. Tran TPY, Leduc K, Savard M, Dupré N, Rivest D, Nguyen DK. Acute porphyria presenting as epilepsia partialis continua. Case Rep Neurol. 2013;5:116–24.

    Article  Google Scholar 

  19. Bonkovsky HL, Dixon N, Rudnick S. Pathogenesis and clinical features of the acute hepatic porphyrias (AHPs). Mol Genet Metab. 2019;128:213–8.

    Article  CAS  Google Scholar 

  20. Jaramillo-Calle DA, Solano JM, Rabinstein AA, Bonkovsky HL. Porphyria-induced posterior reversible encephalopathy syndrome and central nervous system dysfunction. Mol Genet Metab. 2019;128:242–53.

    Article  CAS  Google Scholar 

  21. Price RS, Kasner SE. Hypertension and hypertensive encephalopathy. Handb Clin Neurol. 2014;119:161–7.

    Article  Google Scholar 

  22. Alqwaifly M, Bril V, Dodig D. Acute intermittent porphyria: a report of 3 cases with neuropathy. CRN. 2019;11:32–6.

    Google Scholar 

  23. Mutluay B, Köksal A, Çelık RGG, Bülbül HH. A case of acute intermittent porphyria mimicking Guillain-Barré syndrome. Noro Psikiyatr Ars. 2019;56:311–2.

    PubMed  PubMed Central  Google Scholar 

  24. Rad N, Beydoun SR. Porphyria-induced recurrent quadriplegia misdiagnosed as Guillain-Barré syndrome. US Neurol. 2020;16:66.

    Article  Google Scholar 

  25. Barraza G, Serranova T, Herrero C, Casanova-Mollá J, To-Figueras J, Herranz J, Valls-Solé J. Brainstem dysfunction in variegate porphyria. Muscle Nerve. 2012;46:426–33.

    Article  Google Scholar 

  26. Spiritos Z, Salvador S, Mosquera D, Wilder J. Acute intermittent porphyria: current perspectives and case presentation. TCRM. 2019;15:1443–51.

    Article  CAS  Google Scholar 

  27. Nabin A, Thapa LJ, Paudel R, Rana PVS. Acute intermittent porphyria with SIADH and fluctuating dysautonomia. Kathmandu Univ Med J. 2012;10:96–9.

    Article  CAS  Google Scholar 

  28. Baumann K, Kauppinen R. Long-term follow-up of acute porphyria in female patients: update of clinical outcome and life expectancy. Mol Genet Metab Rep. 2022;30: 100842 (•• Large database of porphyria cases with long-term follow-up providing insight into frequency of complications.).

    Article  CAS  Google Scholar 

  29. Ricci A, Di Pierro E, Marcacci M, Ventura P. Mechanisms of neuronal damage in acute hepatic porphyrias. Diagnostics (Basel). 2021;11:2205 (• Detailed description of the pathogenic mechanisms associated with neuronal damage in porphyrias.).

    Article  CAS  Google Scholar 

  30. Hermes-Lima M, Castilho RF, Valle VG, Bechara EJ, Vercesi AE. Calcium-dependent mitochondrial oxidative damage promoted by 5-aminolevulinic acid. Biochim Biophys Acta. 1992;1180:201–6.

    Article  CAS  Google Scholar 

  31. Emanuelli T, Pagel FW, Porciúncula LO, Souza DO. Effects of 5-aminolevulinic acid on the glutamatergic neurotransmission. Neurochem Int. 2003;42:115–21.

    Article  CAS  Google Scholar 

  32. Müller WE, Snyder SH. delta-Aminolevulinic acid: influences on synaptic GABA receptor binding may explain CNS symptoms of porphyria. Ann Neurol. 1977;2:340–2.

    Article  Google Scholar 

  33. Russell VA, Lamm MC, Taljaard JJ. Inhibition of Na+, K+-ATPase activity by delta-aminolevulinic acid. Neurochem Res. 1983;8:1407–15.

    Article  CAS  Google Scholar 

  34. Lin CS-, Krishnan AV, Lee M, Zagami AS, You H, Yang C, Bostock H, Kiernan MC. Nerve function and dysfunction in acute intermittent porphyria. Brain . 2008;131:2510–2519.

  35. Bredt DS, Hwang PM, Snyder SH. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990;347:768–70.

    Article  CAS  Google Scholar 

  36. •• The drug database for acute porphyria. Available at: http://www.drugs-porphyria.org/. Accessed April 11, 2022. (Updated database containing safety of drugs in porphyria.)

  37. •• American Porphyria Foundation Drug Database. Available at: https://porphyriafoundation.org/drugdatabase/. Accessed Apr 11, 2022. (Updated database containing safety of drugs in porphyria.)

  38. Vidaurre J, Gedela S, Yarosz S. Antiepileptic drugs and liver disease. Pediatr Neurol. 2017;77:23–36.

    Article  Google Scholar 

  39. Syed YY. Givosiran: a review in acute hepatic porphyria. Drugs. 2021;81:841–8.

    Article  CAS  Google Scholar 

  40. Stein P, Badminton M, Barth J, Rees D, Stewart MF. Best practice guidelines on clinical management of acute attacks of porphyria and their complications. Ann Clin Biochem. 2013;50:217–23.

    Article  Google Scholar 

  41. Bissell DM, Anderson KE, Bonkovsky HL. Porphyria. N Engl J Med. 2017;377:862–72.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology and Rehabilitation, University of Illinois at Chicago College of Medicine, 912 S Wood St, Chicago, IL, 60612, USA

    Kyle Wylie & Fernando D. Testai

Authors
  1. Kyle Wylie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fernando D. Testai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kyle Wylie.

Ethics declarations

Conflict of Interest

Kyle Wylie and Fernando D. Testai each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Neurology of Systemic Diseases

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wylie, K., Testai, F.D. Neurological Manifestations of Acute Porphyrias. Curr Neurol Neurosci Rep 22, 355–362 (2022). https://doi.org/10.1007/s11910-022-01205-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11910-022-01205-7

Keywords

Search

Navigation