Download Amanita poisonings resulting in acute, reversible

Nephrol Dial Transplant (2012) 27: 1380–1386
doi: 10.1093/ndt/gfr511
Advance Access publication 29 September 2011
Original Articles
Amanita poisonings resulting in acute, reversible renal failure: new
cases, new toxic Amanita mushrooms
Martin Kirchmair1,*, Patrı́cia Carrilho2,*, Rudi Pfab3, Bettina Haberl3, Joana Felgueiras2,
Fernanda Carvalho4, José Cardoso5, Ireneia Melo5, José Vinhas2 and Sigrid Neuhauser1
1
Institute of Microbiology, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria, 2Centro Hospitalar de Setubal, Rua Camilo
Castelo Branco, Setubal, Portugal, 3Toxikologische Abt., 2. Med. Klinik, Klinikum rechts der Isar, Technische Universität München,
München, Germany, 4Hospital Curry Cabral, Lisboa, Portugal and 5Botanic Garden (NMNH) of Lisbon University, Lisbon, Portugal
Correspondence and offprint requests to: Martin Kirchmair; E-mail: [email protected]
*Both authors contributed equally to this work.
Abstract
Background. Renal failure as a consequence of eating
mushrooms has been reported repeatedly after ingestion of
webcaps of the Cortinarius orellanus group. But mushrooms
of the genus Amanita can also cause renal failure: Amanita
smithiana (North America) and Amanita proxima (Mediterranean area). Here, we discuss poisonings caused by other white
amanitas. A German and—independently—two Portuguese
patients reported the ingestion of completely white mushrooms with ring. Similar to intoxications with A. smithiana
or A. proxima, the clinical picture was characterized by nausea
and vomiting 10–12 h after ingestion, severe acute renal failure and mild hepatitis. Renal biopsy showed acute interstitial
nephritis and tubular necrosis. Two patients were given
temporary haemodialysis. All have fully recovered their renal
function. Poisonings caused by mushrooms containing the
toxin of A. smithiana were suspected. We tested 20 Amanita
species for the presence of this toxin.
Methods. Thin layer chromatography was applied to detect
A. smithiana nephrotoxin in herbarium specimens using
authentic material of A. smithiana as reference.
Results. A. smithiana toxin could be detected in Amanita
boudieri, Amanita gracilior and in Amanita echinocephala.
A. boudieri was collected by the Portuguese patients. A.
echinocephala is the only nephrotoxic Amanita growing
North of the Alps and is suspected to be the cause of renal
failure in the German patient. No A. smithiana toxin was
detectable in the nephrotoxic A. proxima.
Conclusions. A. boudieri, A. gracilior and A. echinocephala are nephrotoxic. These intoxications are clinically
similar to that of A. smithiana, with acute reversible renal
failure and mild hepatitis but are different in their clinical
picture from Orellanus syndrome characterized by a
delayed onset of severe and often irreversible renal failure.
Keywords: Amanita boudieri; Amanita echinocephala; mushroom
intoxication; thin layer chromatography; toxicology
Introduction
Collecting wild mushrooms for food has been a longstanding tradition in many European countries; however,
edible and toxic species are often confused. Although every
‘mushroom hunters’ guide’ warns its readers against collecting unknown or not well-known fungi, several ‘old wives’
tales’ like testing the fruiting bodies with a silver spoon or
checking for insect damage are still used to distinguish edible and poisonous mushrooms. These practices together
with tasting unknown edible mushrooms can lead to severe
mushroom poisonings because (i) macro-fungi can hardly
be reliably identified by comparing pictures in a field guide
with specimens from the wild, (ii) the ‘gastronomic value’ of
rarer species is often not known and therefore (iii) new
poisonous species are discovered occasionally such as those
described here.
The fungal genus Amanita is divided into seven sections
[1]. Mushrooms belonging to the sections Caesareae (Caesar’s
Amanita: Amanita caesaria) and Vaginatae (grisette) are
edible. Poisonous species can be found in all other sections
of the genus (Table 1). The death caps (Amanita phalloides,
Amanita virosa; section Phalloideae) contain hepatotoxic
cyclopeptides (amatoxins, phalloidin) and cause fulminant
hepatical and renal failures that are, if at all, treatable only
symptomatically [2]. The section Amanita contains the quintessential toadstool Amanita muscaria (fly agaric). Toxic
species of the section Amanita contain the neurotoxins
ibotenic acid and muscimol. In the section Validae, slightly
toxic mushrooms containing bufotenine and/or haemolytic
toxins can be found (false death cap: Amanita citrina, [3]). In
sections Lepidella and Amidella, edible and nephrotoxic
fungi are known. Among the genus Amanita, the North
American Lepidella Amantia smithiana [4–11] and the
Mediterranean Amidella Amantia proxima are repeatedly
reported to be nephrotoxic [12–17]. Nevertheless, in
Europe, Amanita poisonings resulting in renal failure are
rare. Most severe renal failures can be traced back to
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Amanita poisonings resulting in renal failure
1381
Table 1. Occurrence of Amanita smithiana toxin, amatoxins and allenic norleucine (2-amino-4,5-hexadienoic acid) in Amanita species
Section Lepidella
A. abrupta
A. boudieri
A. chlorinosma
A. echinocephala
A. gracilior
A. singeri
A. smithiana
A. strobiliformis
A. virgineoidesd
A. vittatini
Section Amidella
A. lepiotoides
A. ovoidea
A. neoovoidead
A. proxima
Section Phalloideae
A. phalloides
A. pseudoporphyriad
Section A
A. gemmata
A. muscaria
Section Validae
A. citrina
Section Cesareae
A. cesarea
Section Vaginatae
A. vaginata
Symptomsa
A. smithiana toxin
Amatoxins/Phallotoxinsb
(h)
n
g
n
(n)
n.k.
n
e
n
e
–
1
–
1
1
–
1
–
–
–
–
–
–
–
–
–
–
–
(e)
e
n
n
–
–
–
–
–
–
g/n/h
n
–
–
1
p
p
–
–
–
–
p
–
–
e
–
–
e
–
–
2-amino-4,5-hexadienoic
acidc
1
1
1
1
a
e, edible; g, gastrointestinal symptoms; h, hepatotoxic; n, nephrotoxic; p, psychoactive; n.k., not known; (): suspected but not proven.
Data from [18].
c
Data from [19].
d
Not tested within this study.
b
ingestion of poisonous webcaps (Cortinarius spp., Section
Orellani; [20, 21]). The Portuguese and German patients reported to have eaten mushrooms resembling white Amanita
species. The symptoms were similar to intoxications with A.
smithiana or A. proxima but these species could be excluded as
discussed below. It became evident that there are more nephrotoxic mushrooms than is currently known. Motivated by
these cases, we tested 20 Amanita species for the presence
of the A. smithiana nephrotoxin.
Materials and methods
Material examined
Amanita abrupta Peck: IB 2000/0537 (NC). Amanita boudieri Barla:
LISU n. 211410 (Portugal). Amanita chlorinosma (Peck) Lloyd: IB
2000/0506 (NC). A. citrina Pers.: no voucher material (Italy). Amanita
echinocephala (Vitt.) Quel. (¼ Amanita solitaria sensu auct. mult.): IB
2001/0264 (Italy); IB 1977/0203 (France, Provence); IB 1995/1093 (Austria); IB 2010/0110 (Italy). Amanita gemmata (Fr.) Bertill: LISU n.
211411 (Portugal). Amanita gracilior Bas: IB 1996/0255 (France). Amanita lepiotoides Barla ss. Gilbert, Cetto: IB 1979/0869 (Italy); IB 1980/
0861 (Italy). A. lepiotoides Barla: IB 1978/0561 (Italy); IB 1977/0311
(Italy); IB 1977/0180 (Italy); IB 1976/0480 (Italy). A. muscaria (L.) Lam.
IB 2002/0161 (Austria). Amanita ovoidea (Bull.: Fr.) Quel.: IB 1982/0532
(France); IB 1972/0476 (Israel); MA-Fungi 53355 (Spain); MA-Fungi
68917 (Spain). A. phalloides (Vaill.) Secr: IB 2007/0350 (Austria). A. proxima Dumée: MA-Fungi 74268 (Spain), MA-Fungi 69238 (Spain). Amanita
rubescens (Pers. ex Fr.) SF Gray: IB 2005/0624 (Italy). Amanita singeri Bas:
IB 1986/0540 (Italy). A. smithiana Bas (¼ A. solitaria sensu Hotson 1936):
IB 1995/0357 (OR). IB1991/0995 (OR, voucher material of Pelizzari et al.
[22]). Amanita strobiliformis (Paulet ex Vittad.) Bertill. (¼ A. solitaria sensu
NCL 1960): IB 2010/0020 (Austria) IB 1998/0504 (Austria). Amanita vaginata (Bull.) Lam.: IB 2005/0647 (Italy). Amanita vittatini (Mor.) Sacc.: IB
1998/0766 (Spain), IB 1998/0830 (Spain).
Thin layer chromatography (TLC)
Dried basidiomata (0.1 g) were ground and suspended in 1 mL 50% watery
methanol for 30 min. This raw extract was filtered through filter paper
(Macherey–Nagel Mn 615¼) and 2 lL were spotted onto TLC plates (silica
gel 60, Merck 105721) or HPTLC plates (high performance TLC plates;
silica gel 60, Merck 105631). Chromatograms were developed using methanol–isopropanol–water–acetic acid–acetic acetate (5:8:12:15:40) as solvent
system [22]. The A.smithiana toxin was detected by spraying developed
TLC plates with a ninhydrine solution, Ehrlich reagent, Morgan–Elson
reagent or anisic aldehyde sulphuric acid according to [23] (Table 2). As
reference for the A. smithiana toxin, a raw extract of voucher material of A.
smithiana [22] was used because the toxin of A. smithiana is not fully
determined and therefore no purified toxin is available. The toxin of A.
smithiana can be detected at an Rf of 0.44 and stains orange–red with
ninhydrine reagent, yellow with anisic aldehyde—sulphuric acid and yellow
with Morgan–Elson reagent [24]. The detection of amatoxins and phalloidine
was carried out according to [25]: 2 lL fruiting body extract were spotted onto
TLC plates (silica gel 60, Merck 105721) using 2-butoxyethanol-25% watery
ammonium hydroxide (7:3) plus 0.2% v/v cinnamic aldehyde as solvent
system. Amatoxins can be detected as violet spots at Rf ¼ 0.39 (a-amanitin)
or Rf ¼ 0.33 (ß-amanitin) after exposing the chromatogram to HCl vapour.
Results
Case reports
Portugal. A 51-year-old woman and her 47-year-old
husband, previously healthy, collected mushrooms in a
1382
M. Kirchmair et al.
Table 2. Spray reagents for TLC [23]
Reagent
Detection of
Recipe
Staining
Morgan–Elson reagent
Amino sugars
Red
Ehrlichs reagent
Amines
Ninhydrine
Amino acids, amines,
amino sugars
Anisic aldehyde
sulphuric acid
Sugars, terpenes,
steroids, etc.
Solution 1: mix 0.5 mL 0.01%
KOH in 80% ethanol (w/v) with 10 mL 1%
acetylaceton in 1-butanol (v/v)
Solution 2: mix 1 g 4-(dimethylamino)
benzaldehyde in 30 mL ethanol
with 30 mL 36% HCl
Heat after spraying with Solution 1 for 5 min at
105C; spray with Solution 2 and
heat for 5 min at 90C
Solution 1: 1% 4-(dimethylamino)
benzaldehyde in 9% methanolic HCl
Solution 2: 1% 4-(dimethylamino)
benzaldehyde in 96% watery ethanol
Heat after spraying with Solution 1;
spray with Solution 2 and heat
0.3 g ninhydrine, 100 mL butanol,
3 mL acetic acid
Heat at 110C after spraying
0.5 mL anisic aldehyde,
1 mL sulphuric acid in 50 mL
glacial acetic acid
Heat at 100–105C after spraying
small forest, near Lisbon, in Portugal in April 2010. They
had two consecutive mushroom meals (dinner and next
day’s lunch), ingesting ~500 g of mushrooms in total. The
woman complained about anorexia, nausea and vomiting the
next day. Five days later, as the complaints still persisted and
she additionally noticed weakness and a reduction of diuresis, she went to hospital. On admission, she was normotensive, apparently euvolaemic, afebrile, without relevant
findings on physical examination. Initial laboratory tests revealed severe renal failure with creatinine 11.7 mg dL1
(normal: <1.2), blood urea nitrogen (BUN) 68.18 mg
dL1 (<18) and a mild hepatic cytolysis with elevation of
alanine aminotransferase (ALT) 64 U L1 (10–35). Urine
analysis revealed density 1010, pH 5.5, trace blood and
protein. Urine microscopy showed >75 white blood cells
lL1, 10 red blood cells lL1 and no casts. No pathogens
were detectable in urine or stool. Renal ultrasound showed
the left kidney to be 123 mm in length and the right kidney
122 mm. Both were echogenic with prominent renal
pyramids and no hydronephrosis. No pathogens grew on
culture of urine or stool.
Haemodialysis was initiated, through a temporary right
internal jugular vein dialysis catheter. On the presumption
that they had eaten an orellanine-containing mushroom, therapy was started with antioxidant and steroids, as suggested
by Kilner et al. [26]. The patient was started on prednisolone
60 mg once a day and oral N-acetylcysteine 600 mg every
6 h. Her renal function improved over the course of the next
days, and she became independent of dialysis 5 days after
admission (10 days after mushroom ingestion; BUN 45.02
mg dL1 and a creatinine of 2.2 mg dL1). After 2 months,
her BUN was 15.9 mg dL1 and creatinine 1.0 mg dL1.
The patient’s 47-year-old husband, who had ingested a
smaller amount of the mushroom meals, had mild dyspepsia
and anorexia, and he did not spontaneously seek for medical
help. He was asked to be submitted to clinical and laboratory
Various
Yellow, orange, red
Violet, red, blue,
grey, green
evaluation. He was also found to have significant renal
impairment (BUN 50.0 mg dL1, creatinine 8.6 mg
dL1) and mild elevations of ALT (69 U L1) and aspartate aminotransferase (AST) (32 U L1). Leucocytes
count 7800 lL1. Urinalysis revealed pH 5.5, density
1020, trace proteins and some erythrocytes and rare leucocytes. Other laboratory tests were normal. His physical
examination was unremarkable. He was not given dialysis.
Treatment as described above with prednisone and oral Nacetylcysteine was initiated. On the fourth day of admission, a biopsy of his left kidney was made (Figure 1a and
b). It showed marked focal interstitial lymphocytic infiltrate with areas of tubular necrosis. The glomeruli appeared normal, apart from one ischaemic glomerulus.
Arterioles were normal. Immunofluorescence for immunoglobulin deposits and complement was negative. These
aspects were compatible with acute interstitial nephritis.
His renal function improved, with serum creatinine of
4.5mg dL1 at day 10 after ingestion of mushrooms.
Two months later, his serum creatinine was 0.8 mg dL1.
After discharge, the patients re-collected some mushrooms at the original place. Specimens were identified at
the Botanic Garden (NMNH) of Lisbon University as A.
boudieri (Figure 2a) and A. gemmata. Later, staff from the
Botanic Garden accompanied the patients to the field and
asked them to point at the mushrooms they had picked.
Again, the same two species were collected.
Germany. A 55-year-old hitherto healthy woman, native
of Italy, was admitted to a Munich hospital, October 1997,
48 h after a meal of ~500 g fresh mushrooms. She had
collected the mushrooms herself in a public park near
Munich and sautéed them well before eating. She described
the mushrooms as white with a flaked hat, white gills, a
white ring and a bulb. She claimed to have eaten this type
Amanita poisonings resulting in renal failure
1383
Fig. 1. Renal biopsy. (a) Diffuse interstitial infiltrate, normal glomerulus and tubular necrosis (periodic acid-schiff 3250). (b) Diffuse interstitial
infiltrate with eosinophils (haematoxylin and eosin 3400).
of mushroom all her life and tested its edibility with a silver
spoon that did not turn black. Starting 6 h after the meal,
she suffered nausea, vomiting and diarrhoea ~10 h after
the meal.
As the vomiting did not stop the day after the mushroom
meal, she was admitted to hospital. There she also complained about visual disturbances. Her physical examination
showed no pathologies except for a slight hypertension (160/
90 mmHg) and dry mucous membranes. The first laboratory
tests showed normal liver function tests except for bilirubine
2.3 mg dL1 but an acute renal failure with creatinine 5.2 mg
dL1; BUN 48 mg dL1. Other laboratory findings included
lactate dehydrogenase 326 U L1 (<240), C-reactive protein
2.3 mg dL1 (<0.5), potassium 2.01 mmol L1 (3.5–5.0),
leucocytes 12 500 lL1 (400–9000). At the time of admittance, the diarrhoea and vomiting had stopped, but she soon
developed renal failure with preserved water diuresis, mild
proteinuria (0.66 g1) with a tubular protein pattern. Tests for
anti-nuclear antibodies, extractable nuclear antigen, anti-neutrophil cytoplasmic antibody, circulating immunocomplexes,
C3-complement, puumula- and hanta-virus were negative.
A renal biopsy was performed 4 days after the meal and
showed massive tubular necrosis with eosinophil casts in
the tubular lumina a minimal lymphphocytic infiltration of
the interstitium. No signs of vascular or glomerular damage
were seen. The type of renal lesion may be typical for a toxic
damage. A kidney biopsy specimen was tested for the presence of orellanine according to Rohrmoser et al. [21]. No
orellanine was detected. The renal function deteriorated so
four sessions of haemodialysis were necessary until the renal
function fully recovered within 20 days after the meal.
Already at admittance, the patient had reported visual
disturbances, which did not improve despite the complete
recovery of the renal failure. An ophthalmologic examination showed a regular ocular fundus and regular anterior
chamber. The functional tests revealed a total loss of colour
vision and defects in the upper visual fields in both eyes,
fitting for a toxic atrophy of the optic nerve. A follow-up
examination after 4 weeks showed normal renal and liver
function tests but no improvement of her visus.
The cause of the renal failure remained unclear as the
Orellanus syndrome had to be excluded because of the
negative biopsy sample, the early onset of symptoms and
the fact that the patient ate white mushrooms only (Cortinarius
orellanus and Cortinarius rubellus are brown). The two white
mushrooms that are known to cause similar symptoms—the
North American Amanita smithiana and the strict Mediterranean A. proxima—do not grow around Munich but there are
records of A. echinocephala (Figure 2b; [27])—a mushroom
shown to contain a nephrotoxin in this paper.
Detection of A. smithiana toxin in voucher material
of Amanita species
The toxin of A. smithiana is detectable applying the TLC
system described above at an Rf of 0.44, stains orange red
with ninhydrine and yellow with Morgan–Elson and
Ehrlich reagent [22,24]. The spot at Rf ¼ 0.4 of extracts
of voucher material used to identify the A. smithiana toxin
by Pelizzari et al. [22] showed identical reactions. Fruiting
body extracts of all A. smithiana collections, A. gracilior, A.
boudieri and A. echinocephala reacted like the A. smithiana
voucher material (Figure 2c). All these species are closely
related and belong to the section Lepidella. In extracts of the
edible Lepidella A. strobiliformis, the toxin was not detectable.
The A. smithiana toxin was not detectable in the nephrotoxic
A. proxima, a species of section Amidella and in any other
species investigated in this study.
Amatoxins and phalloidin could be detected only in A.
phalloides.
Discussion
Several Amanita spp. of the section Lepidella are known to
cause renal failure including the North American
1384
M. Kirchmair et al.
Fig. 2. Nephrotoxic Amanita spp. (a) Fruitbody of Amantia boudieri (LISU n. 211410). (b) Fruitbody of Amanita echinocephala (IB 2010/0110). (c)
Thin layer chromatogram of fruitbody extracts of A. echinocephala (IB 2010/0110), Amanita boudieri (LISU n. 211410), Amanita gemmata (LISU n.
211411), Amanita gracilior (IB 1996/0255), Amanita smithiana (voucher material of Pelizzari et al. [22]), Amanita phalloides (IB 2007/0350). The spot
of the A. smithiana toxin is visible at an Rf ¼ 0.44 (arrow) in extracts of A. echinocephala, A. boudieri, A. gracilior, and A. smithiana after spraying with
ninhydrine.
A. smithiana, which is the best known among these nephrotoxic species [4–11]. The symptoms of our patients conform to those known from A. smithiana intoxications
(Table 3). These symptoms start with nausea and vomiting
2–12 h (average 6 h) after the mushroom meal. Renal failure occurs 2–6 days (average 3.5 days) after ingestion.
Patients receive supportive treatment, usually requiring
temporary haemodialysis, but their prognosis is good. Similar symptoms are reported after ingestion of North and
Middle American Amanita thiersii and Amanita nauseosa
(both section Lepidella, [1]). There is also a report of renal
failure after eating Amanita virgineoides [28], although this
mushroom is sold on Chinese markets [1]. In a case of acute
renal failure from Taiwan, a fungus morphologically similar to A. smithiana was eaten [29]: 6 h after their meal, the
two patients suffered abdominal pain, nausea and vomiting.
One patient became anuric a few days later. Also, the second
patient developed a minor renal disorder obvious by slightly
increased creatinine but no haemodialysis was necessary.
Both patients recovered fully.
Until now, no nephrotoxic European species of section
Lepidella has been identified. The Portuguese patients had
symptoms characterized by reversible severe acute renal
failure due to acute interstitial nephritis and mild hepatic
cytolysis 5 days after ingestion of the mushrooms. The
mushrooms responsible for the intoxication could be identified as A. boudieri by examining mushrooms re-collected
by the patients. The A. smithiana toxin could be detected in
the dried fruiting bodies. The patient from Germany
exhibited similar symptoms as the Portuguese patients.
Although from this case, no leftovers were available for
examination—it is very likely that A. echinocephala was
the cause of this poisoning. Fruiting bodies of A. echinocephala contain A. smithiana toxin. It is the only white
Lepidella known to occur around Munich [27].
In contrast to all reported cases of poisonings with
A. smithiana, the German patient suffered from visual disorders, a symptom that has been reported before only once
in connection with mushroom poisoning [30]. The authors
report on an A. phalloides intoxication and discussed inter
alia, and thereby provoked taurine depletion as possible
cause of the visual impairment. The actual significance to
our case remains speculative as we did not test the amino
acid levels of the patient.
Renal failure can also be caused by Amanita spp. section
Amidella. Most intoxications are reported from Southern
Europe where A. proxima can be confused with the morphologically very similar, edible A. ovoidea [12–17].
Amanita poisonings resulting in renal failure
1385
Table 3. Mushroom intoxications accompanied by renal failure (data summarized from [8,10,13–17,31])
Gastro intestinal symptoms
(vomiting, nausea): median delay
Renal failure: median delay
GPT (3normal value; median)
GOT (3normal value; median)
Outcome (recovery/chronic renal
insufficiency/death) in %
Amanita
smithiana (n ¼ 9)
Amanita
proxima (n ¼ 7)
Cortinarius orellanus
group (n ¼ 82)
6 hours
11 hours
3 days
3.5 days
1.8
1.0
100/0/0
2 days
5.6
2.3
100/0/0
8.5 days
1 (?)
1 (?)
40.3/51.6/8.1
Besides the darker volva of A. proxima, the two species are
nearly indistinguishable in their macroscopically and microscopically morphological characters. Spores of both
species are elliptical and similar in size. A ‘tennis racket
aspect of the spores’ of A. proxima was pictured by Courtin
et al. [17]. It is likely that they observed germinating spores
of their fresh A. proxima collection and misinterpreted as
distinguishing character. The clinical manifestation of
A. proxima intoxications is similar to A. smithiana intoxications, but no A. smithiana toxin was detectable in herbarium specimens. The different nature of the A. proxima
nephrotoxin(s) needs more attention in future studies.
Also, other fungi of the section Amidella have been
reported to cause renal failure, a Japanese patient developed gastrointestinal symptoms 9 h after eating Amantia
neoovoidea and was hospitalized 2 days later with acute
renal failure [32]. However, A. neoovidea is thought to be
edible (for example, as tempura or in soups; [1]).
Delayed renal failure is also known from members of
Section Phalloidea. In the case of A. phalloides, renal failure is
probably mediated by toxic cyclopeptides (amatoxins, phalloidin [33]). Amanita pseudoporphyria (section Phalloidea)
can cause renal failure with symptoms similar to an A. smithiana intoxication; however, no clear gastrointestinal symptoms develop and the renal symptoms appear later [34].
There is no evidence that A. pseudoporphyria contains
amatoxins or phallotoxins, but it contains 2-amino-4,
5-hexadienoic acid, otherwise known from some mushrooms
of section Lepidella [35]. A. pseudoporphyria is still considered as member of the section Phalloidae, but according to
recent taxonomic analyses, it is possibly a member of Lepidella
rather than of Phalloidea [36,37].
The nephrotoxin of Lepidella mushrooms is usually
thought to be the allenic norleucine 2-amino-4,5-hexadienoic
acid [6,9,29]. This non-protein amino acid has been detected
in A. abrupta [38], A. neoovoidea [39], A. pseudoporphyria
[35] and A. smithiana [19,40,41]. But, there is evidence that
A. smithiana toxin is not identical with the allenic norleucine:
(i) the toxicity and/or content of the amino acid in fruiting
bodies are too low [41]. The LD50 of 2-amino-4,5-hexadienoic acid is >50 mg kg1 (guinea pig, intraperitoneal) [41],
which is high when compared to the fungal nephrotoxin orellanine (LD50 ¼ 8.0 mg kg1 guinea pig, intraperitoneal) [42].
A. smithiana contains 0.1% allenic norleucine [41], while the
orellanine content of C. rubellus is 1.2% dry weight1 [21].
The deadly dose rate for an 80 kg person would therefore be 4
kg dried A. smithiana mushrooms (~400 fruiting bodies). (ii)
In the hepatotoxic (but not nephrotoxic) A. abrupta [38], the
allenic norleucine was detected, but the A. smithiana toxin
could not be detected in our study. The exact nature of
A. smithiana toxin remains unclear. The toxin reacts with
ninhydrine on TLC, which argues for amino groups. Pellizari
et al. [22] misinterpreted the toxin as an amino sugar, which
can be detected by the specific red staining with Morgan–
Elson reagent [23] but the A. smithiana toxin stains yellow
[24]. Future studies are necessary to elucidate the nature and
the mode of action of the toxin.
It is important for the medical community to be aware of
nephrotoxic mushrooms of the genus Amanita. We identified three nephrotoxic species besides A. smithiana and A.
proxima: the strictly Mediterranean species A. boudieri and
A. gracilior and A. echinocephala known from temperate
regions all over Europe. The ‘Amanita nephrotoxic syndrome’ is characterized by an early onset of gastrointestinal
symptoms, mild hepatic damage and severe but reversible
acute renal failure due to acute interstitial nephritis (Table
3). It must be separated from the well-known Orellanus
syndrome, characterized by the absence of gastrointestinal
symptoms and a delayed onset of renal failure with a very
bad prognosis.
Acknowledgements. We thank Frank H. Gleason for constructive comments and suggestions during the preparation of this paper. The authors
thank Reinhold Pöder for passing on his knowledge and expertise and
Sarah Peer for technical work. We are indebted to Dr Fátima Pinho
Almeida for identifying Portuguese specimens of Amanita.
Conflict of interest statement. None declared.
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Received for publication: 21.4.11; Accepted in revised form: 28.7.11