Clinical Toxicology, 39(4), 413–416 (2001)

PLANT POISONINGS

Amatoxin Poisoning from Ingestionof Japanese Galerina Mushrooms

Hiroaki Kaneko,1,* Takeshi Tomomasa,1 Yoshinari Inoue,1

Fumio Kunimoto,1 Toshio Fukusato,2 Shinjiro Muraoka,3

Kunio Gonmori,4 Tetsuo Matsumoto,5

and Akihiro Morikawa1

1Gunma University School of Medicine, Maebashi, Japan2Gunma University Hospital, Maebashi, Japan3Mori & Company, Ltd., Kiryu, Japan4Akita University School of Medicine, Akita, Japan5Gunma Prefectural Forestry Research Laboratory, Sinto, Japan

ABSTRACT

Background: Although some Japanese Galerina species poisonings manifest as gas-trointestinal symptoms followed by late-onset hepatorenal failure (phalloides syn-drome), the toxin responsible for this has not been determined. Case Report: Wereport a 6-year-old boy who developed characteristic cholera-like diarrhea andlate-onset severe hepatic deterioration after eating mushrooms, later identified asa Galerina species, most likely Galerina fasciculata. A residual mushroom revealedα-amanitin. This account is the first known reported case of poisoning by JapaneseGalerina species where an amatoxin was demonstrated to be responsible for thetoxicity.

INTRODUCTION

Human mushroom poisoning can be classified ac-cording to the clinical symptoms. Phalloides syndrome(PS) is a type of mushroom poisoning characterized bygastrointestinal symptoms (abdominal pain, vomiting,

* Correspondence: Dr. Hiroaki Kaneko, Department of Pediatrics, Gunma University School of Medicine, 3-39-15 Showa-machi,Maebashi, Gunma 371-8511, Japan. Fax 81/27-220-8215; E-mail: hkaneko@showa.gunma-u.ac.jp

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Copyright 2001 by Marcel Dekker, Inc. www.dekker.com

and cholera-like diarrhea) followed by late-onset hepato-renal dysfunction. The toxicity in PS results mainly fromα-amanitin, one of the amatoxins (1).

Some mushrooms of the Japanese Galerina speciescause poisoning (2,3). Among them, Galerina fasciculatapoisoning has been reported only in Japan. The toxins

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414 Kaneko et al.

responsible for symptoms of G. fasciculata poisoninghave not been determined. Although amatoxins are pro-posed, given the similarity of symptoms and time course(3,4), Muraoka et al. recently reported detection of aman-itins in G. fasciculata harvested in Japan (5). Althoughthe strains of mushroom they studied were not those thatcaused actual poisoning, their finding supports the associ-ation found in this case report.

We report a patient who developed cholera-like diar-rhea and severe late-onset hepatic failure after eating astrain of wild mushrooms in which α-amanitin was de-tected. Morphologically, this mushroom was identified asa Galerina species, probably G. fasciculata, but possiblya previously undescribed Galerina species.

Case Report

A 6-year-old boy ate soup containing wild mushroomswith his family at 2100 hours. The mushrooms had beenfound in a cluster upon rotting wood and had been har-vested by the patient’s grandfather. The next morning,approximately 6–10 hours after ingestion, the boy devel-oped abdominal pain, nausea, vomiting, and diarrhea.Five members of his family who had also eaten the souphad similar but less severe symptoms. Two other personswho did not eat the soup developed no symptoms. Unlikeother family members who gradually improved, the boydeveloped moderate dehydration from continued vom-iting and diarrhea. At 36 hours after ingestion, he washospitalized with the diagnosis of mushroom poisoning.His blood chemistry test results on admission showedmoderately elevated liver enzyme levels—aspartate ami-notransferase (AST) 136 IU/L (normal: 10–22 IU/L) andalanine aminotransferase (ALT) 117 IU/L (normal: 5–21 IU/L). The patient was treated with intravenous hy-dration, but general fatigue persisted. The diarrhea wasat first watery, then became whitish as in cholera, andthen became bloody. Blood tests approximately 62 hoursafter ingestion showed severe hepatic insufficiency [AST18450 IU/L; ALT 13554 IU/L; total bilirubin 0.9 mg/dL (normal: 0.3–1.2 mg/dL); ammonia 93 µg/dL (nor-mal: 3–47 µg/dL)] with low total hemolytic complement(CH50) �5 U/mL (normal: 30.0–45.0 U/mL) and aprolonged prothrombin time (PT) 25.8 sec (normal:9.3–13.4 sec). Although blood urea nitrogen and serumcreatinine were not elevated, urinalysis showed mildproteinuria, glycosuria, and hematuria, with hyaline andgranular casts.

The patient was transferred to our hospital 72 hoursafter ingestion because of fulminant hepatic failure. Lab-

oratory data on admission were AST 8492 IU/L; ALT9977 IU/L; total bilirubin 1.6 mg/dL; PT 24.7 sec; am-monia 106 µg/dL. Because of the highly elevated ASTand ALT with minimal elevation of serum bilirubin leveland because his level of consciousness seemed disturbed,a Reye-like syndrome was suspected and therefore twoplasma exchanges combined with continuous hemodia-filtration for 48 hours were started immediately. Amatox-ins were suspected as the cause for mushroom poisoningdue to history and typical clinical features. For detoxifi-cation, activated charcoal was administered repeatedlytogether with a cathartic. Two days after the transfer,blood chemistry and coagulation values had markedlyimproved: AST 53 IU/L; ALT 254 IU/L; PT 11.5 sec;and CH50 42.3 U/mL. He developed elevation of plasmapancreatic enzyme levels 5 days after ingestion withoutclinical signs or symptoms of pancreatitis (amylase 1316IU/L, normal: 120–340 IU/L; lipase 63.7 IU/L, normal:6.1–29.4 IU/L), which was only transient. Histopatho-logic findings in a liver biopsy specimen obtained at 90

Figure 1. Mushrooms in the present case, taken from thesame cluster as other mushrooms harvested and prepared forsoup. Mycologists morphologically assigned residual mush-rooms to the Galerina genus. Bar � 1 cm.

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Amatoxin in Japanese Galerina Poisoning 415

Figure 2. Chromatogram of extract from the Galerina speciesshown in Figure 1, obtained by high performance liquid chro-matography. Separation conditions are described in a previousreport by Muraoka et al. (5). Detection and identification of theamanitin were performed at UV 295 nm and UV spectral analy-sis, respectively. The peak eluted at 18.3 min corresponded toα-amanitin.

hours following ingestion showed marked fatty degenera-tion and severe centrilobular coagulation necrosis. Hissubsequent course was favorable, and all blood valuesreturned to normal by the hospital day 18 (AST 34 IU/L; ALT 27 IU/L; total bilirubin 6.8 µmol/L[0.4 mg/dL];PT 11.0 sec; and CH50 48.9 IU/L).

Three mycologists morphologically assigned to theGalerina genus residual mushrooms obtained from thesame cluster as those prepared for the soup. Althoughconclusive morphological identification of the Galerinamushrooms at the species level was difficult, all mycolo-gists agreed that the mushroom was most likely to be G.fasciculata (Fig. 1). Although no amatoxins were detect-able in the patient’s urine or blood at 80 hours after inges-tion, α-amanitin was detected in a residual mushroom byhigh-performance liquid chromatography (Fig. 2).

DISCUSSION

Koppel et al. distinguished seven types of mushroompoisoning based on the patients’ symptoms (1). PS iscaused by amatoxins which are cyclopeptides that caninhibit RNA polymerases. Amatoxins induce abdominalpain, nausea, vomiting, and cholera-like diarrhea after arelatively long latent period (8–10 hours on average).Later, as these gastrointestinal symptoms decrease, late-

onset hepatorenal deterioration can ensue. Severe casesdevelop fulminant hepatic failure, sometimes accompa-nied by acute renal failure. Patients requiring liver trans-plantation or who have died from progressive encepha-lopathy have been reported (6).

Some mushrooms of the Galerina species in Japan areknown to cause poisoning (2,3). Fifty-three Japanese pa-tients with G. fasciculata poisoning, including 5 fatalcases, have been reported over three decades (2). Al-though the characteristic clinical features resemble PScaused by amatoxins, these toxins have not been detectedeither in the fruiting body of the fungus or in samplesfrom patients (3,4).

Recently, Muraoka et al. reported detection of amani-tins in some strains of Galerina species harvested in Ja-pan, including G. fasciculate (5). The poisonous mush-room that caused PS in our case was classified in theGalerina genus and contained α-amanitin. Although con-clusive morphologic identification of the species couldnot be made, only G. fasciculata among Galerina specieshas been reported to cause PS, according to the summarydata for 10,924 Japanese cases of mushroom poisoningfrom 1959 to 1988 (2). Therefore, this poisonous mush-room is very likely to be G. fasciculata or, less likely, apreviously undescribed Galerina species.

In our patient’s family, only the 6-year-old boy whoate more soup than others developed severe liver dys-function. Age as well as dose may have been important;amatoxin poisoning has higher lethality in children thanin adults (7). Detection of α-amanitin in the mushroomin this case provides strong evidence that amatoxins areresponsible for severe hepatic failure in patients withGalerina species poisoning. Amatoxins usually remaindetectable in plasma up to only 36 hours, and in urineup to only 4 days (8). Therefore, α- or β-amanitin couldnot have been detected in the plasma taken from our pa-tient 80 hours after ingestion, and may have disappearedfrom the urine as well. No correlation has been observedbetween α-amanitin plasma concentration and clinicalsymptoms (6).

The plasma pancreatic enzymes showed a transient el-evation in the present case, and acute pancreatitis waspresumably caused by α-amanitin in this Galerina spe-cies. Half of patients with Amanita poisoning had clinicalor biochemical evidence of pancreatitis (9).

Hypocomplementemia occurs occasionally in Ama-nita poisoning, as in general severe hepatic insufficiencycaused by viral hepatitis or toxic substances, which canresult in complement depression from both high con-sumption and deficient synthesis. The rapid return of

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CH50 to a normal level in the present case reflected anoverall clinical improvement (10).

This case of mushroom poisoning from a Galerinaspecies containing α-amanitin defines α-amanitin as re-sponsible for PS caused by Japanese Galerina species.

ACKNOWLEDGEMENTS

We thank Mr. H. Neda of Kyushu Research Center,Forestry and Forest Products Research Institute, and Mr.E. Nagasawa of The Tottori Mycological Institute foridentification of the mushroom in this case.

REFERENCES

1. Koppel, C. Clinical Symptomatology and Managementof Mushroom Poisoning. Toxicon 1993, 31 (12), 1513–1540.

2. Ishihara, Y.; Yamaura, Y. Descriptive EpidemiologyMushroom Poisoning in Japan. (in Japanese) Jpn. J. Hyg.1992, 46 (6), 1071–1078.

3. Yamashita, M.; Furukawa, H. Amanitatokisin-gun. InKinoko-chudoku, 1st Edition. (in Japanese); Kyoritsu-shuppan: Tokyo, 1993; 109–122.

4. Yamaura, Y.; Nakamura, K.; Ishihara, Y. Descriptive Ep-idemiology Mushroom Poisoning in Nagano Prefecture.(in Japanese) Shokuhin-eiseigaku-zasshi 1997, 38 (2),110–115.

5. Muraoka, S.; Fukamachi, N.; Mizumoto, K.; Shiozawa,T. Detection and Identification of Amanitins in theWood-Rotting Fungi Galerina fasciculata and Galerinahelvoliceps. Appl. Environ. Microbiol. 1999, 65 (9),4207–4210.

6. Klein, A.S.; Hart, J.; Brems, J.J.; Goldstein, L.; Lewin,K.; Busuttil, R.W. Amanita Poisoning: Treatment and theRole of Liver Transplantation. Am. J. Med. 1989, 86 (2),187–193.

7. Floersheim, G.L.; Weber, O.; Tschumi, P.; Ulbrich, M.Clinical Death-Cap (Amanita phalloides) Poisoning:Prognostic Factors and Therapeutic Measures. Analysisof 205 Cases. (in German) Schweiz Med Wochenschr1982, 112 (34), 1164–1177.

8. Jaeger, A.; Jehl, F.; Flesch, F.; Sauder, P.; KopferschmittJ. Kinetics of Amatoxins in Human Poisoning: Therapeu-tic Implications. J. Toxicol. Clin. Toxicol. 1993, 31 (1),63–80.

9. Castiella, A.; Cosme, A.; Arenas, J.I. Acute Pancreatitis.N. Engl. J. Med. 1994, 331 (14), 949.

10. Dupuy, C.; Dupuy, J.M. Complement Studies in SevereViral Hepatitis of Childhood. Pathol. Biol. (Paris) 1977,25 (8), 553–558.

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