Mushroom poisonings are common in the United States. Gyromitrin (acetaldehyde N-methyl-N-formylhydrazone) is a clinically significant mycotoxin primarily associated with the lorchel (i.e. the false morel) Gyromitra esculenta. Resemblance between 'true and false morels' has resulted in misidentification of Gyromitra spp. as edible and sought after Morchella spp., resulting in toxicity. Despite literature evidence outlining toxic sequalae, Gyromitra spp. mushrooms are commonly consumed and prepared for culinary purposes. Classic clinical teachings emphasize significant neurotoxicity, including seizures, associated with ingestion of gyromitrin-containing mushrooms, stemming from gyromitrin's terminal metabolite monomethylhydrazine. We performed a longitudinal descriptive review of the clinical toxicity associated with ingestion of mushroom species known or suspected to contain gyromitrin in cases reported to the Michigan Poison & Drug Information Center between January 1, 2002, to December 31, 2020. Our 19-year descriptive case series of gyromitrin-containing mushroom ingestions reported to our Center demonstrated a preponderance of gastrointestinal signs and symptoms, including hepatotoxicity. Of 118 identified cases, 108 (91.5%) of the reported ingestions involved Gyromitra esculenta. The most frequent clinical findings associated with symptomatic ingestions (n = 83) were the aforementioned gastrointestinal symptoms (n = 62; 74.7%). Neurological symptoms were less frequent (n = 22, 26.5%) while hepatotoxicity occurred in fewer patients (n = 14; 16.9%). Of symptomatic patients, most were treated with symptomatic and supportive care (n = 58; 70%). Pyridoxine was used in a total of seven patients (n = 7; 8.4%) with either hepatotoxicity or neurotoxicity. Medical outcomes ranged from minor to major, with no reported deaths. Patient presentations (i.e. GI vs. neurotoxic symptoms) following ingestion of gyromitrin-containing mushrooms may be highly variable and multifactorial, owing to differences in dose ingested, geographical distribution, genetic variability of both patient and mushroom species, and species-specific differences in toxin composition. Future research warrants species-level identification of ingested gyromitrin-containing mushrooms and investigating the contribution of genetic polymorphisms to differences in clinical toxidromes.

Gyromitra esculenta, the false morel mushroom, has a unique toxicity profile. The mushroom derives its name, esculenta, from the Latin for edible. Certain cultures consider this mushroom safe to eat, provided that proper preparation techniques (such as par-boiling) are used to reduce its toxicity. Unfortunately, several incidences of poisoning have been reported in foragers seeking and ingesting the Gyromitra esculenta. Most poisonings occur when foragers search for true morels, such as Morchella species, but instead find and consume Gyromitra. The Gyromitra syndrome consists of a gastrointestinal prodrome occurring more than 5 hours after eating Gyromitra esculenta. Acute liver injury can occur over the next 2 days in a significant percentage of cases, and acute kidney injury may occur to a lesser degree. Confusion characterizes acute central nervous system (CNS) toxicity in many instances. However, in the most severe instances, refractory seizures may occur but are rare. This is the consequence of the pharmacology of gyromitrin’s toxic metabolite, monomethylhydrazine (MMH). Monomethylhydrazine binds to and inhibits pyridoxal phosphokinase, thereby inhibiting the activation of vitamin B6 (pyridoxal 5-phosphate) from functioning as the key cofactor in the synthesis of GABA. The subsequent depletion of GABA leads to CNS excitation and seizures.

Species of Discinaceae are common macrofungi with a worldwide distribution. Some of them are commercially consumed, while a few others are reported as poisonous. Two genera were accepted in the family: the epigeous Gyromitra with discoid, cerebriform to saddle-shaped ascomata and the hypogeous Hydnotrya with globose or tuberous ascomata. However, due to discrepancies in their ecological behaviors, a comprehensive investigation of their relationship was not thoroughly explored. In this study, phylogenies of Discinaceae were reconstructed using sequence analyses of combined and separate three gene partitions (internal transcribed spacer [ITS], large subunit ribosomal DNA [LSU], and translation elongation factor [TEF]) with a matrix containing 116 samples. As a result, the taxonomy of the family was renewed. Eight genera were recognized: two of them (Gyromitra and Hydnotrya) were retained, three (Discina, Paradiscina, and Pseudorhizina) were revived, and three (Paragyromitra, Pseudodiscina, and Pseudoverpa) were newly established. Nine new combinations were made in four genera. Two new species in Paragyromitra and Pseudodiscina and an un-named taxon of Discina were described and illustrated in detail based on the materials collected from China. Furthermore, a key to the genera of the family was also provided. IMPORTANCE Taxonomy of the fungal family Discinaceae (Pezizales, Ascomycota) was significantly renewed on the basis of sequence analyses of internal transcribed spacer (ITS), large subunit ribosomal DNA (LSU), and translation elongation factor (TEF). Eight genera were accepted, including three new genera; two new species were described; and nine new combinations were made. A key to the accepted genera of the family is provided. The aim of this study is to deepen the understanding of the phylogenetic relationships among genera of the group, as well as the associated generic concepts.

Gyromitrin (acetaldehyde N-methyl-N-formylhydrazone) and its homologs are deadly mycotoxins produced most infamously by the lorchel (also known as false morel) Gyromitra esculenta, which is paradoxically consumed as a delicacy in some parts of the world. There is much speculation about the presence of gyromitrin in other species of the lorchel family (Discinaceae), but no studies have broadly assessed its distribution. Given the history of poisonings associated with the consumption of G. esculenta and G. ambigua, we hypothesized that gyromitrin evolved in the last common ancestor of these taxa and would be present in their descendants with adaptive loss of function in the nested truffle clade, Hydnotrya. To test this hypothesis, we developed a sensitive analytical derivatization method for the detection of gyromitrin using 2,4-dinitrobenzaldehyde as the derivatization reagent. In total, we analyzed 66 specimens for the presence of gyromitrin over 105 tests. Moreover, we sequenced the nuc rDNA internal transcribed spacer region ITS1-5.8S-ITS2 (ITS barcode) and nuc 28S rDNA to assist in species identification and to infer a supporting phylogenetic tree. We detected gyromitrin in all tested specimens from the G. esculenta group as well as G. leucoxantha. This distribution is consistent with a model of rapid evolution coupled with horizontal transfer, which is typical for secondary metabolites. We clarified that gyromitrin production in Discinaceae is both discontinuous and more limited than previously thought. Further research is required to elucidate the gyromitrin biosynthesis gene cluster and its evolutionary history in lorchels.

With mushroom poisoning emerging as one of the most serious food safety problems worldwide, a rapid identification method of poisonous mushrooms is urgently required to investigate the source of poisoning. Gyromitra infula, a kind of poisonous mushroom, contains gyromitrin toxin, which causes epileptogenic neurotoxicity and hemolytic disease. This study aimed to establish a rapid and visual method of G. infula identification based on loop-mediated isothermal amplification (LAMP). A set of specific LAMP primers was designed, and its specificity in G. infula was confirmed against various mushroom species, including its closely related species and other macrofungi. The sensitivity assay showed that the minimum concentration of genomic DNA detected by LAMP was 1 ng/μl. The method's applicability was conducted by preparing mushroom samples that were boiled and digested in artificial gastric juice. The results showed that the content as low as 1% G. infula can be successfully detected. This method can be completed within 90 min, and the reaction results can be directly observed by the naked eyes. Hence, the identification method of G. infula established based on LAMP in this study is accurate, rapid, sensitive, and low-cost, which is required for clinical treatment or forensic analysis when mushroom poisoning occurs.

Between 1990 and 2018, 14 cases of amyotrophic lateral sclerosis (ALS) were diagnosed in residents of, and in visitors with second homes to, a mountainous hamlet in the French Alps. Systematic investigation revealed a socio-professional network that connected ALS cases. Genetic risk factors for ALS were excluded. Several known environmental factors were scrutinized and eliminated, notably lead and other chemical contaminants in soil, water or home-grown vegetation used for food, radon and electromagnetic fields. Some lifestyle-related behavioral risk factors were identified: Prior to clinical onset of motor neuron disease, some patients had a high degree of athleticism and smoked tobacco. Recent investigations on site, based on a new hypothesis, showed that all patients had ingested wild mushrooms, notably poisonous False Morels. Half of the ALS cohort reported acute illness following Gyromitra gigas mushroom consumption. This finding supports the hypothesis that genotoxins of fungal origin may induce motor neuron degeneration.

Recently, consumption of the gyromitrin-containing neurotoxic mushroom Gyromitra sp. (false morel), as gourmet food was hypothesized to play a role in sporadic amyotrophic lateral sclerosis genesis. The present review analyses recent data on edibility and toxicity of false and true morels and Agaricus spp. Controversy about the toxic status of Gyromitra esculenta was due to variable toxin susceptibility within consumers. We suggest that Verpa bohemica, another false morel, is also inedible. We found a temporary neurological syndrome (NS) with cerebellar signs associated with high consumption of fresh or dried true morels Morchella sp. After ingestion of crude or poorly cooked fresh or dried morels, a gastrointestinal "haemolytic" syndrome was also observed. Agaritine, a water soluble hydrazinic toxin closely related to gyromitrin is present along with metabolites including diazonium ions and free radicals, in Agaricus spp. and A. bisporus, the button mushroom, and in mice after ingestion. It is a potential weak carcinogen in mice, but although no data are available for humans, a lifetime low cumulative extra cancer risk in humans can be estimated to be about 10-5. To conclude, a safety measure is to avoid consuming any true morels or button mushrooms when crude or poorly cooked, fresh or dried.

Gyromitra esculenta, also known as "false morel" is one of the most poisonous mushrooms. This species is found all over the world, growing in coniferous forest in early spring time. Common manifestation of poisoning includes gastrointestinal symptoms which include varied degrees of liver impairment. We describe three cases: acute liver injury, acute liver failure and acute-on-chronic liver failure due to G. esculenta poisoning. At admission patients presented with encephalopathy and features of liver failure. Two of them recovered completely following supportive management while the remaining patient who also had preexisting liver disease developed multiorgan failure and subsequently died. Although a rare occurrence, G. esculenta poisoning should be considered in the differential diagnosis of acute liver failure.

Gyromitra species are known as "false morels" and produce cerebriform or discoid ascocarps. The genus is widely distributed in the Northern Hemisphere, and some species are poisonous. Infrageneric phylogenies based on 28S nuc rDNA (28S) are available, but molecular analyses derived from other genes are lacking. In this study, Gyromitra specimens deposited in HMAS were reexamined. Phylogenies inferred from 28S, nuc rDNA internal transcribed spacers (ITS1-5.8S-ITS2 = ITS), and the translation elongation factor 1-α (TEF1) gene were obtained, and four clades were revealed among 13 species. Two new cryptic species of Gyromitra, G. pseudogigas, sp. nov. and G. tianshanensis, sp. nov., are described. Gyromitra pseudogigas has saddle-shaped apothecia similar to those of G. infula and is sister to G. gigas in the phylogeny. Gyromitra tianshanensis clusters with G. infula and G. xinjiangensis but differs in morphology and sequence data.

The present study was undertaken with a view to improving forensic medical diagnostics of intoxication with poisonous mushrooms in the cases of patients' death in a hospital. A total of 15 protocols of forensic medical examination of the corpses of the people who had died from acute poisoning were available for the analysis. The deathly toxins were amanitin and muscarine contained in various combinations in the death cap (Amanita phalloides) and the early false morels (Gyromitra esculenta and G. gigas). The main poisoning season in the former case was May and in the latter case August and September (93.4%). The mortality rate in the case of group intoxication (such cases accounted for 40% of the total) amounted to 28.6%. 40% of the deceased subjects consumed mushrooms together with alcohol. The poisoning caused the development of either phalloidin- or gyromitrin-intoxication syndromes (after consumption of Amanita phalloides and Gyromitra esculenta respectively). It is emphasized that the forensic medical experts must substantiate the diagnosis of poisoning with mushroom toxins based on the results of the chemical-toxicological and/or forensic chemical investigations. The relevant materials taken from the victim or the corpse should be dispatched for analysis not only within the first day but also on days 2-4 after intoxication. The mycological and genetic analysis must include the detection and identification of mushroom microparticles and spores in the smears from the oral cavity, vomiting matter, wash water, gastric and intestinal contents. In addition, the macro- and microscopic morphological signs, clinical data (major syndromes, results of laboratory studies, methods of treatment) should be taken into consideration as well as the time (season) of mushroom gathering, simultaneous poisoning in a group of people, and other pertinent information.