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Toxicity, Mushroom - Gyromitra Toxin

Author: Reed Brozen, MD, Director of Air Transport, Associate Professor, Department of Emergency Medicine, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center
Coauthor(s): Marcus J Hampers, MD, MBA, Instructor, Department of Medicine, Dartmouth Medical School; Consulting Staff, Department of Internal Medicine, Section of Hospital Medicine, Department of Anesthesiology, Section of Critical Care Medicine, and Department of Emergency Medicine, Dartmouth Hitchcock Medical Center
Contributor Information and Disclosures

Updated: Feb 29, 2008

Introduction

Background

Thousands of mushroom species are studied and collected by amateur mushroom hunters, but only a handful cause death. False morel mushrooms (eg, Gyromitra esculenta, Gyromitra ambigua, Gyromitra infula) can cause fatal poisonings. These mushrooms are found on the ground or on rotten wood, are orange-brown to brown, have no gills, and have convoluted brainlike caps that are occasionally saddle-shaped. Gyromitra species fruit in the spring, and most poisonings occur during spring or early summer.

Pathophysiology

Some Gyromitra mushrooms contain hydrazones, including the toxin gyromitrin (N -methyl-N-formylhydrazone). Gyromitrin rapidly decomposes in the stomach to form acetaldehyde and N -methyl-N-formylhydrazine, which is converted to monomethylhydrazine (MMH) by slow hydrolysis. MMH is a water-soluble toxin that causes gastroenteritis, hemolysis, methemoglobinemia, hepatorenal failure, seizures, and coma. MMH is employed in rocket fuel and causes similar toxicity in aerospace industry workers. Cooking can render these mushrooms less toxic, although not reliably so. MMH is volatile and the fumes from cooking may cause toxicity.

Neurotoxicity

MMH exposure is similar to that of isoniazid in that it generates functional pyridoxine deficiency by inhibition of pyridoxine kinase. Pyridoxine kinase inhibition interferes with production of pyridoxal phosphate, an essential cofactor for a number of enzymatic steps, including glutamic acid decarboxylase (GAD).

Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter of the brain, is produced from glutamate (an excitatory neurotransmitter) by the enzyme GAD. MMH also may inhibit GAD directly. The resultant GABA deficiency, with loss of inhibitory neurotransmission, may lead to seizures.

Gastrointestinal toxicity

Inhibition of diamine oxidase in intestinal mucosa may be responsible for GI effects. Association of individual variability in acetylation rates (eg, slow vs fast acetylators) in hepatotoxicity is not well established.

Hematopoietic toxicity

Hemolysis and methemoglobinemia can occur. Resultant hemoglobinuria may cause renal failure.

Frequency

United States

In 2004, a total of 2,438,644 toxic substance exposures and 1,183 deaths were reported to the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System. Mushroom exposures accounted for 8,601 cases and 5 fatalities.1

  • In the same 2004 report, known gyromitrin-containing mushrooms accounted for 52 exposures and no fatalities. Only 1 fatality was in an unknown mushroom type.1
  • Unknown mushroom type makes up the majority of exposures each year, usually accounting for well over 80% of mushroom exposures, but deaths in this group remain remarkably low (0-2 per year since 1996).
  • In 2003, known gyromitrin-containing mushrooms accounted for 71 exposures and only 1 fatality.2
  • In 2002, gyromitrin-containing mushrooms accounted for 66 exposures and 1 death.3
  • In 2001, gyromitrin-containing mushrooms accounted for 44 exposures and no deaths.4
  • In 2000, gyromitrin-containing mushrooms accounted for 36 exposures and no deaths.5
  • In 1999, gyromitrin-containing mushrooms accounted for 36 exposures but no recognized fatalities.6
  • In 1998, gyromitrin-containing mushrooms accounted for 77 exposures but no deaths.7
  • In 1997, gyromitrin-containing mushrooms accounted for 86 exposures, 3 with major outcomes, but no deaths.8
  • In 1996, gyromitrin-containing mushrooms accounted for 62 exposures but no deaths.9
  • Another study published in May 2000 used data from the National Center for Health Statistics and found no difference from the AAPCC annual report in numbers of deaths caused by mushroom exposures.10

International

No adequate international database exists. In the past, gyromitrin-containing mushrooms have been associated with significant mortality in Eastern Europe.

Mortality/Morbidity

  • Mortality rates from 10-40% have been reported; however, death from gyromitrin-containing mushrooms in North America is exceedingly rare.
  • Toxicity of gyromitrin-containing mushrooms varies by region and season.

Age

  • Children are more sensitive to gyromitrin toxicity than adults.
  • Overall about 60% of mushroom exposures are in children younger than 6 years. Although with Gyromitra species specifically, children younger than 6 years account for only 3% of exposures.

Clinical

History

Determining history of mushroom exposure is helpful. Query patients presenting with gastroenteritis about mushroom collecting, cooking, and ingestion.

  • Onset of symptoms typically is delayed with gyromitrin poisoning.
    • GI symptoms typically occur 6-10 hours after ingestion; however, symptoms may begin earlier with severe poisonings.
    • Symptoms may be delayed 48 hours with mild poisonings.
    • Inhalation exposure characteristically produces symptoms within 2 hours of exposure.
    • GI phase of toxicity may be followed by neurologic and hepatorenal toxicity.
  • Details of ingestion and progression of symptoms are helpful in differentiating ingestions of different mushroom types. Ask the following questions to ascertain specific history:
    • When were the mushrooms ingested (or when was patient exposed to vapors of cooking mushrooms)?
    • When did each symptom begin?
    • Where were the mushrooms found?
    • Were other species ingested?
    • Did others become ill after eating the mushrooms?
  • Clinical history includes the following:
    • GI symptoms are prominent, with complaints of abdominal pain, bloating, vomiting, and diarrhea.
    • Other complaints (eg, weakness, dizziness, headache, confusion, seizures) may be caused by volume depletion, anemia, and renal, hepatic, or neurologic toxicity.
    • Typical duration of symptoms is 1-2 days but may be as long as 5 days.

Physical

  • Vital signs
    • Tachycardia
    • Hypotension
    • Tachypnea (secondary to methemoglobinemia and/or hemolysis)
    • Fever
  • General appearance
    • Dry skin with poor turgor (from vomiting and fluid losses)
    • Pale skin (from hemolysis)
    • Cyanosis unresponsive to oxygen (from methemoglobinemia)
    • Jaundice (from liver damage and hemolysis)
  • Neurologic findings
    • Tremor, muscle spasms
    • Seizures, delirium
    • Stupor and encephalopathy
  • Abdominal and rectal findings
    • Hyperactive bowel sounds, bloating, mild tenderness to palpation
    • Hepatomegaly
    • Liquid or heme-positive stool
  • Hematologic findings
    • Muddy-colored urine from hemoglobinuria (due to hemolysis)
    • Chocolate-colored brown blood (from methemoglobinemia)

Causes

MMH poisoning may occur after ingestion of fresh, dried, or raw gyromitrin-containing mushrooms or with inhalation of vapors while cooking gyromitrin-containing mushrooms.

  • Severity depends on amount of toxin ingested. Amount of toxin greatly varies among mushrooms, and significant variation in individual susceptibility exists.
    • Raw mushrooms have more toxin than cooked mushrooms.
    • Fresh mushrooms have more toxin than dry mushrooms.
    • Environmental factors appear to influence the amount of toxin, which varies regionally in these mushrooms. Michigan has a large number of Gyromitra mushrooms.

More on Toxicity, Mushroom - Gyromitra Toxin

Overview: Toxicity, Mushroom - Gyromitra Toxin
Differential Diagnoses & Workup: Toxicity, Mushroom - Gyromitra Toxin
Treatment & Medication: Toxicity, Mushroom - Gyromitra Toxin
Follow-up: Toxicity, Mushroom - Gyromitra Toxin
References
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References

  1. Watson WA, Litovitz TL, Rodgers GC, et al. 2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2005;23(5):589-666. [Medline].

  2. Watson WA, Litovitz TL, Klein-Schwartz W, et al. 2003 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2004;22(5):335-404. [Medline].

  3. Watson WA, Litovitz TL, Rodgers GC, et al. 2002 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2003;21(5):353-421. [Medline].

  4. Litovitz TL, Klein-Schwartz W, Rodgers GC, et al. 2001 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2002;20(5):391-452. [Medline].

  5. Litovitz TL, Klein-Schwartz W, White S, et al. 2000 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2001;19(5):337-95. [Medline].

  6. Litovitz TL, Klein-Schwartz W, White S, et al. 1999 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2000;18(5):517-74. [Medline].

  7. Litovitz TL, Klein-Schwartz W, Caravati EM, et al. 1998 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1999;17(5):435-87. [Medline].

  8. Litovitz TL, Klein-Schwartz W, Dyer KS, et al. 1997 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1998;16(5):443-97. [Medline].

  9. Litovitz TL, Smilkstein M, Felberg L, et al. 1996 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1997;15(5):447-500. [Medline].

  10. Hoppe-Roberts JM, Lloyd LM, Chyka PA. Poisoning mortality in the United States: comparison of national mortality statistics and poison control center reports. Ann Emerg Med. May 2000;35(5):440-8. [Medline].

  11. Braun R, Greeff U, Netter KJ. Liver injury by the false morel poison gyromitrin. Toxicology. Feb 1979;12(2):155-63. [Medline].

  12. Brent J, Kulig K. Mushrooms. In: Haddad LM, et al, eds. Clinical Management of Poisoning and Drug Overdose. 3rd ed. WB Saunders; 1998:365-74.

  13. Karlson-Stiber C, Persson H. Cytotoxic fungi--an overview. Toxicon. Sep 15 2003;42(4):339-49. [Medline].

  14. Leathem AM, Dorran TJ. Poisoning due to raw Gyromitra esculenta (false morels) west of the Rockies. CJEM. Mar 2007;9(2):127-30. [Medline].

  15. Michelot D, Toth B. Poisoning by Gyromitra esculenta--a review. J Appl Toxicol. Aug 1991;11(4):235-43. [Medline].

  16. Schneider A, Attaran M, Meier PN, Strassburg C, Manns MP, Ott M. Hepatocyte transplantation in an acute liver failure due to mushroom poisoning. Transplantation. Oct 27 2006;82(8):1115-6. [Medline].

  17. Trestrail JH. Monomethylhydrazine-containing mushrooms. In: Spoerke DG, Rumack BH, eds. Handbook of Mushroom Poisoning: Diagnosis and Treatment. CRC Press LLC; 1994:279-87.

  18. Yildirim C, Bayraktaroglu Z, Gunay N, Bozkurt S, Köse A, Yilmaz M. The use of therapeutic plasmapheresis in the treatment of poisoned and snake bite victims: an academic emergency department's experiences. J Clin Apher. Dec 2006;21(4):219-23. [Medline].

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Further Reading

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Keywords

mushroom poisoning, false morel mushrooms, Gyromitra esculenta, Gyromitra ambigua, Gyromitra infula, mushroom toxicity, gyromitra toxin, gyromitra poisoning, hydrazones, N -methyl-N-formylhydrazone, mushroom exposure, gyromitrin-containing mushrooms, poisonous mushrooms

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Contributor Information and Disclosures

Author

Reed Brozen, MD, Director of Air Transport, Associate Professor, Department of Emergency Medicine, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center
Reed Brozen, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, New Hampshire Medical Society, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Marcus J Hampers, MD, MBA, Instructor, Department of Medicine, Dartmouth Medical School; Consulting Staff, Department of Internal Medicine, Section of Hospital Medicine, Department of Anesthesiology, Section of Critical Care Medicine, and Department of Emergency Medicine, Dartmouth Hitchcock Medical Center
Marcus J Hampers, MD, MBA is a member of the following medical societies: American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Medical Association, New Hampshire Medical Society, Society of Critical Care Medicine, and Undersea and Hyperbaric Medical Society
Disclosure: Nothing to disclose.

Medical Editor

B Zane Horowitz, MD, FACMT, Professor, Fellowship Director, Department of Emergency Medicine, Oregon Health and Sciences University; Medical Director, Oregon Poison Center; Medical Director, Alaska Poison Control System
B Zane Horowitz, MD, FACMT is a member of the following medical societies: American Academy of Clinical Toxicology and American College of Medical Toxicology
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, ABAT, Director of Pharmacy, Sacred Heart Hospital
John T VanDeVoort, PharmD, ABAT is a member of the following medical societies: American Academy of Clinical Toxicology and American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

Michael Hodgman, MD, Assistant Clinical Professor of Medicine, Department of Emergency Medicine, Bassett Healthcare
Michael Hodgman, MD is a member of the following medical societies: American College of Medical Toxicology, American College of Physicians, Medical Society of the State of New York, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

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