You are in: eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Toxicology Toxicity, Plants - Ackee FruitArticle Last Updated: Apr 27, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Dave A Holson, MD, MPH, Assistant Professor of Emergency Medicine, Mount Sinai School of Medicine; Director, Department of Emergency Medicine, Queens Hospital Center, Jamaica, NY Dave A Holson is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, National Medical Association, and Society for Academic Emergency Medicine Coauthor(s): Sekuleo Gathers, MD, Department of Emergency Medicine, Staff Physician, Mount Sinai Medical Center; Glendon C Henry, MD, Medical Director, Harlem Hospital Center Editors: Michael E Mullins, MD, Assistant Professor, Department of Emergency Medicine, Washington University School of Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Jeffrey R Tucker, MD, Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center; Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine; Maureen Strafford, MD, Arnold P Gold Foundation Associate Professor, Departments of Anesthesiology and Pediatrics, Tufts University and Tufts-New England Medical Center Author and Editor Disclosure Synonyms and related keywords: ackee fruit, Blighia sapida, akee fruit, unripe akee fruit, unripe ackee fruit, Jamaican vomiting sickness, ackee fruit poisoning, akee fruit poisoning, toxic hypoglycemic syndrome, THS, Ankye, lshin, hypoglycin A, hypoglycin B, hypoglycin, ackee ingestion, unripe ackee ingestion INTRODUCTIONSection 2 of 11
  BackgroundAckee, the national fruit of Jamaica, is a food staple in many Jamaican diets. The ackee tree is a tropical evergreen tree that can grow as tall as 40 feet. Its leaves are broad and pinnate; its approximately 10-cm-wide, 100-g fruit may be colored anywhere from straw to bright red. The fruit splits open while still on the tree to reveal 3 glassy black seeds surrounded by a thick, oily, yellow aril. The ackee tree is indigenous to West Africa, where it is called ankye or ishin. Thomas Clarke, Jamaica's first botanist, introduced the plant to the island in 1778. However, the ackee tree, Blighia sapida, was named after the infamous Captain Bligh who took the breadfruit tree to the West Indies. The tree also grows in other West Indian Islands, in Central America, and in Southern Florida. An association between ackee poisoning and Jamaican vomiting sickness was first noted in 1875 and documented in 1904. In 1937, Jordan and Burrows found a water-soluble toxic material in the seed and pods of the ackee fruit. In 1954, Hass et al were the first to isolate 2 toxic compounds in their crystalline form. These compounds were called hypoglycin A and hypoglycin B because of their hypoglycemic activity. PathophysiologyTwo toxic water-soluble substances can be extracted from the fruit. The first toxin, hypoglycin A, is L-a-amino-b-[methylene cyclopropyl]propionic acid. Hypoglycin B is a g-L-glutamyl derivative of hypoglycin A and is less toxic than hypoglycin A. Hypoglycin A, but not hypoglycin B, can be found in the aril of the fruit. The unripe fruit has a much higher concentration of hypoglycin A than that of the ripe aril. Both components are found in the seeds. Hypoglycin A, which is now simply called hypoglycin, is metabolized by means of transamination and oxidative decarboxylation to methylene cyclopropyl acetic acid (MCPA). MCPA forms nonmetabolizable carnitine and coenzyme A (CoA) esters, thereby depressing tissue levels of these cofactors and making them less available for other biochemical reactions. Hypoglycemia results because both CoA and carnitine are necessary cofactors for long-chain fatty acid oxidation and because oxidation is a requisite for active gluconeogenesis. MCPA also inhibits the dehydrogenation of several acyl-CoA dehydrogenases, including butyryl CoA, glutaryl CoA, and isovaleryl CoA. As a result of the inhibition of butyryl CoA dehydrogenase, the oxidation of long-chain fatty acids stops at the level of hexanoyl CoA and butyryl CoA. This effect leads to the decreased production of nicotinamide adenine dinucleotide (NADH) and acetyl CoA. Because NADH and acetyl CoA are required as a cofactor of 3-phosphoglyceraldehyde phosphate dehydrogenase and as an activator of pyruvate carboxylase, respectively, their diminished concentration contributes to the inhibition of gluconeogenesis. The inhibition of glutaryl CoA dehydrogenase results in the accumulation of glutaryl CoA, which could inhibit transmitochondrial malate transport, a rate-limiting step in the early phase of gluconeogenesis, and consequently suppress gluconeogenesis. Altered levels of circulating insulin do not cause hypoglycemia associated with hypoglycin action. FrequencyUnited StatesAckee is illegal in the United States; therefore, underreporting may occur. To date, 2 cases of ackee poisoning have been reported in the United States. The first was in Ohio in a Jamaican woman who presented with Jamaican vomiting sickness after a meal of ackee fruit. The second was in Connecticut in a young Jamaican man who presented with cholestatic jaundice secondary to the chronic ingestion of ackee fruit. InternationalThe epidemiology of ackee poisoning has not been well characterized, and the true incidence and mortality rate are believed to be underreported. At the request of the Jamaican Ministry of Health (JMH), the Centers for Disease Control and Prevention (CDC) identified 38 cases of Jamaican vomiting sickness and 6 deaths from 1989-1991. This problem is endemic in Jamaica; 271 cases have been reported to the JMH since 1980. In 1998, an unexplained outbreak of epidemic fatal encephalopathy (EFE) occurred in Burkina Faso in West Africa. The only factor associated with EFE was the presence of ackee trees within 100 m of the households. The consumption of unripe ackee fruit possibly caused this epidemic. Mortality/MorbidityBefore treatments were developed, the mortality rate was as high as 80%.
RaceAckee is consumed mostly in Africa and Jamaica; therefore, the most cases have occurred in blacks. SexNo difference exists in the sex distribution. AgeIn Jamaica, the annual rate of ackee poisoning is 2 cases per 100,000 persons younger than 15 years and 0.4 case per 100,000 persons older than 15 years. CLINICALSection 3 of 11
HistoryJamaican vomiting sickness is characterized by a sudden onset of vomiting that is preceded by generalized epigastric discomfort starting 2-6 hours after the ingestion of a meal containing ackee. Once the sickness begins, symptom progression is rapid. After a period of prostration, which may last as long as 18 hours, a second bout of vomiting may occur. Unless treatment is given, this episode is usually followed by convulsions, coma, and death.
PhysicalThe general physical examination is important in deciding how aggressively to resuscitate the patient. Observed clinical manifestations, listed by degree of severity, are as follows:
Causes
DIFFERENTIALSSection 4 of 11
Biotin Deficiency Glycogen-Storage Disease Type 0 Glycogen-Storage Disease Type I Glycogen-Storage Disease Type II Glycogen-Storage Disease Type III Glycogen-Storage Disease Type IV Glycogen-Storage Disease Type V Glycogen-Storage Disease Type VI Glycogen-Storage Disease Type VII Hyperinsulinemia
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| Drug Name | Dextrose (D-glucose) |
|---|---|
| Description | Used to promptly increase serum glucose level. Monosaccharide absorbed from intestine and distributed, stored, and used by tissues. Patients may recover if IV dextrose is administered before permanent damage due to low blood glucose levels occurs. |
| Adult Dose | 0.5-1 g/kg (1-2 mL/kg) IV; not to exceed 25 g (50 mL) of 50% solution; may follow with continuous IV infusion prn |
| Pediatric Dose | 0.5-1 g/kg IV of 25% or 10% dextrose in water; followed by IV infusion to match normal hepatic glucose production (~5-8 mg/kg/min in infants, ~3-5 mg/kg/min in older children); adjust dose to maintain plasma glucose level >2.5 mmol/L |
| Contraindications | Do not administer in diabetic coma if blood sugar levels are extremely high; avoid in severe dehydration; do not administer concentrated solution in intraspinal or intracranial hemorrhage; avoid in dehydrated patients with delirium tremens, hepatic coma, or glucose-galactose malabsorption syndrome |
| Interactions | Caution with coadministered drugs that may increase blood glucose level; caution when administering parenteral fluids to patients receiving corticosteroids or corticotropin, especially if solution contains sodium ions |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | May cause dilution of serum electrolytes or overhydration in cases of fluid overload; caution in congestion or pulmonary edema; hypertonic dextrose given peripherally may cause thrombosis (administer through central venous catheter instead); caution in subclinical diabetes mellitus or carbohydrate intolerance; rapid administration increases risk of significant hyperglycemia or hyperosmolar syndrome, especially in chronic uremia or carbohydrate intolerance; do not administer concentrated solutions SC or IM; infusion rates >0.5 g/kg/h may produce glycosuria (incidence at rates of 0.8 g/kg/h, 5%); closely monitor fluid balance, electrolyte concentrations, and acid-base balance; may produce vitamin B-complex deficiency |
| Drug Name | Glucagon |
|---|---|
| Description | Polypeptide hormone identical to human glucagon; acts only on liver glycogen, converting it to glucose; do not use as empiric therapy because patients tend to be glycogen-depleted and may not improve; may be used temporarily until IV access obtained. |
| Adult Dose | 1 mg IM/SC |
| Pediatric Dose | <10 kg: 0.1 mg/kg/dose IM/SC; not to exceed 1 mg >10 kg: Administer as in adults |
| Contraindications | Documented hypersensitivity; pheochromocytoma |
| Interactions | May enhance effects of anticoagulants (although onset may be delayed); monitor PT activity and for signs of bleeding in patients receiving anticoagulants; adjust dose accordingly |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | May not be effective in glycogen depletion (eg, alcoholism, old age, malnourishment, young age); do not use if IV access readily available |
Insulin secretion may be altered by various mechanisms. Diazoxide inhibits pancreatic secretion of insulin, stimulates glucose release from the liver, and stimulates catecholamine release, which elevates blood glucose levels. Octreotide is a peptide with pharmacologic action similar to that of somatostatin, which inhibits insulin secretion.
| Drug Name | Diazoxide (Hyperstat IV) |
|---|---|
| Description | Reserved for severe persistent hypoglycemia. Increases blood glucose by inhibiting pancreatic insulin release, possibly through an extrapancreatic effect. |
| Adult Dose | 300 mg IV over 30 min; may repeat q4h |
| Pediatric Dose | 3-5 mg/kg IV; not to exceed 150 mg/dose |
| Contraindications | Documented hypersensitivity to diazoxide, thiazides, or other sulfonamide derivatives; aortic coarctation, pheochromocytoma, arteriovenous shunts, and aortic aneurysm |
| Interactions | May decrease serum hydantoins, possibly decreasing anticonvulsant effects; thiazide diuretics may potentiate hyperuricemic and antihypertensive effects |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Causes BP to rapidly decrease (continuous BP monitoring required); repeated injections can result in sodium and water retention (especially important in impaired cardiac reserve) |
| Drug Name | Octreotide (Sandostatin) |
|---|---|
| Description | Acts primarily on somatostatin receptor subtypes II and V. Inhibits GH secretion and has multiple endocrine and nonendocrine effects, including inhibition of glucagon, VIP, and GI peptides. Highly effective in treatment of hypoglycemia caused by sulfonylurea overdose. Despite lack of published descriptions of its use in Jamaican vomiting sickness, may be useful in this setting. |
| Adult Dose | 50 mcg SC tid; may increase to 500 mcg tid; doses of 300-600 mcg/d or higher seldom have additional biochemical benefit |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | May reduce effects of cyclosporine; may need to adjust dose in patients taking insulin, oral hypoglycemics, beta-blockers, or calcium channel blockers |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Adverse effects primarily related to altered GI motility and include nausea, abdominal pain, diarrhea, and increased prevalence of gallstones and biliary sludge; because of alteration in levels of counterregulatory hormones (insulin, glucagon, GH), hypoglycemia or hyperglycemia may occur; bradycardia, cardiac conduction abnormalities, and arrhythmias reported; because of inhibition of TSH secretion, hypothyroidism may occur; caution in renal impairment; cholelithiasis may occur |
These agents are used to control vomiting associated with ackee fruit poisoning.
| Drug Name | Prochlorperazine (Compazine) |
|---|---|
| Description | A phenothiazine derivative. May relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors with its anticholinergic effects and by depressing reticular activating system. |
| Adult Dose | 5-10 mg IV over at least 2 min; 25 mg PR q12h |
| Pediatric Dose | <2 years or <10 kg: Not recommended >2 years: 0.1-0.15 mg/kg/dose PO/PR q12h |
| Contraindications | Documented hypersensitivity; bone marrow suppression, narrow-angle glaucoma, and severe liver or cardiac disease |
| Interactions | Coadministration with other CNS depressants or anticonvulsants may cause additive effects; coadministration with epinephrine may cause hypotension |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Drug-induced Parkinson syndrome or pseudoparkinsonism is frequent; akathisia is most common extrapyramidal reaction in elderly patients; lowers seizure threshold; caution in history of seizures; high prevalence of extrapyramidal effects observed in children |
| Drug Name | Promethazine (Phenergan) |
|---|---|
| Description | Phenothiazine derivative. Has antihistaminic, sedative, anti–motion sickness, antiemetic, and anticholinergic effects. |
| Adult Dose | 12.5-25 mg IV/IM/PR q4-6h |
| Pediatric Dose | <2 years: Contraindicated 0.25-0.5 mg/kg IV/IM/PR q6h |
| Contraindications | Documented hypersensitivity; comatose states; children younger than 2 y (incidences of death due to respiratory depression) |
| Interactions | May have additive effects when used concurrently with other CNS depressants or anticonvulsants; coadministration with epinephrine may cause hypotension |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in cardiovascular disease, impaired liver function, seizures, sleep apnea, and asthma |
| Drug Name | Metoclopramide (Reglan) |
|---|---|
| Description | Stimulates motility of upper GI tract. Dopamine antagonist that stimulates acetylcholine release in myenteric plexus. Acts centrally on chemoreceptor triggers in floor of fourth ventricle, providing important antiemetic activity. |
| Adult Dose | 10 mg IV/IM q2-3h prn |
| Pediatric Dose | 0.5 - 2 mg/kg IV q2-4h prn; not to exceed adult dose |
| Contraindications | Documented hypersensitivity; pheochromocytoma or GI hemorrhage, obstruction or perforation; history of seizure disorders |
| Interactions | May antagonize effects of metoclopramide; opiate analgesics may increase toxicity in CNS |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Extrapyramidal reactions can occur; caution in history of mental illness and Parkinson disease |
These act in the GABA-benzodiazepine receptor complex and are used to control seizures.
| Drug Name | Lorazepam (Ativan) |
|---|---|
| Description | Sedative hypnotic with short onset of effects and relatively long half-life. May depress all levels of CNS, including limbic and reticular formation, by increasing action of GABA (major inhibitory neurotransmitter in brain). |
| Adult Dose | 4 mg IV bolus |
| Pediatric Dose | 0.05 mg/kg IV slowly, repeat once in 15 min prn |
| Contraindications | Documented hypersensitivity; preexisting CNS depression, hypotension, and narrow-angle glaucoma |
| Interactions | Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease |
| Drug Name | Diazepam (Valium) |
|---|---|
| Description | Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. |
| Adult Dose | 5-10 mg IV q10-15min; not to exceed 30 mg |
| Pediatric Dose | 1 mg IV q2-5min; not to exceed 10 mg slow IV administration |
| Contraindications | Documented hypersensitivity; acute narrow-angle glaucoma |
| Interactions | Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity) |
| Media file 1: Freshly picked Ackee fruit | |
 | View Full Size Image | Media type: Photo |
| Media file 2: Black seeds surrounded by a thick, oily, yellow aril (edible portion). | |
 | View Full Size Image | Media type: Photo |
Toxicity, Plants - Ackee Fruit excerpt
Article Last Updated: Apr 27, 2006
