Jamaican vomiting sickness, also known as toxic hypoglycemic syndrome (THS),
acute ackee fruit intoxication, or ackee poisoning,
is an acute illness caused by the toxins
hypoglycin A
Hypoglycin A is a naturally occurring amino acid derivative found in the unripened fruit of the Ackee tree ('' Blighia sapida'') and in the seeds of the box elder tree (''Acer negundo''). It is toxic if ingested, and is the causative agent of Jam ...
and
hypoglycin B
Hypoglycin B is a naturally occurring organic compound in the species '' Blighia sapida''. It is particularly concentrated in the fruit of the plant especially in the seeds. Hypoglycin B is toxic if ingested and is one of the causative agents of ...
, which are present in fruit of the
ackee tree. Unripe arils contain concentrations of hypoglycin A that are 20-fold higher than those of ripe arils,
and can cause vomiting and even death. Some countries in the Caribbean and Western Africa experience frequent cases.
Presentation
Abdominal discomfort begins two to six hours after eating unripe
ackee fruit, followed by sudden onset vomiting. In severe cases, profound dehydration, seizures, coma, and death may ensue. Children and those who are malnourished are more susceptible to the disease.
Pathophysiology
When ingested, hypoglycin A is metabolized to produce
methylenecyclopropylacetic acid (MCPA). MCPA acts to inhibit the
beta-oxidation
In biochemistry and metabolism, beta oxidation (also β-oxidation) is the Catabolism, catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA. Acetyl ...
of fatty acids in two ways. First, it interferes with the transport of long-chain fatty acids into the mitochondria by forming ester linkages with
carnitine
Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids from the cytosol into mitochondria to be oxidized for f ...
and
coenzyme A
Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the Fatty acid metabolism#Synthesis, synthesis and Fatty acid metabolism#.CE.B2-Oxidation, oxidation of fatty acids, and the oxidation of pyruvic acid, pyruvate in the citric ac ...
(CoA).
Also, it inhibits
acyl-CoA dehydrogenases,
so that only unsaturated fatty acids can be fully oxidized. Fatty acids accumulate in the liver in a microvesicular pattern that can be seen on biopsy. In the absence of fatty acid metabolism, the body becomes dependent on glucose and glycogen for energy.
Octreotide
Octreotide, sold under the brand name Sandostatin among others, is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. It was ...
can be used to reduce the secretion of insulin by the pancreas, thereby preventing severe
hypoglycemia
Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...
.
Inhibition of beta-oxidation of fatty acids, however, also depletes nicotinamide adenine dinucleotide (
NADH
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an ade ...
) and
acetyl CoA
Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized fo ...
—the latter an activator of
pyruvate carboxylase
Pyruvate carboxylase (PC) encoded by the gene PC is an enzyme () of the ligase class that catalyzes (depending on the species) the physiologically irreversible carboxylation of pyruvate to form oxaloacetate (OAA).
Image:Pyruvic-acid-2D-ske ...
—inhibiting
gluconeogenesis
Gluconeogenesis (GNG) is a metabolic pathway that results in the biosynthesis of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In verte ...
. Once the liver glycogen stores are depleted, the body cannot synthesize glucose, and severe hypoglycemia results.
Initial symptoms appear after about four hours, and deaths have been reported from 12 to 48 hours following consumption. Supportive care involves carefully metered IV glucose infusion and fluid/electrolyte replacement; mortality was 80% before glucose infusion was introduced in 1954.
A similar outbreak of lethal hypoglycemic
encephalopathy
Encephalopathy (; ) means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome ...
has been linked to the consumption of
lychee
Lychee ( , ; ''Litchi chinensis''; ) is a monotypic taxon and the sole member in the genus ''Litchi'' in the soapberry family, Sapindaceae.
There are three distinct subspecies of lychee. The most common is the Indochinese lychee found in So ...
fruit in
Muzaffarpur, India.
Urinalysis
Urinalysis, a portmanteau of the words ''urine'' and ''analysis'', is a Test panel, panel of medical tests that includes physical (macroscopic) examination of the urine, chemical evaluation using urine test strips, and #Microscopic examination, m ...
of children affected by the disease has shown all affected have elevated levels of
hypoglycin suggesting the same underlying pathophysiology as Jamaican vomiting sickness.
Diagnosis
In popular culture
The disease appears in the ''
ER'' episode "
Great Expectations
''Great Expectations'' is the thirteenth novel by English author Charles Dickens and his penultimate completed novel. The novel is a bildungsroman and depicts the education of an orphan nicknamed Pip. It is Dickens' second novel, after ''Dav ...
", where the symptoms are recognised by
Dr. Mallucci who, it is later revealed, attended medical school in
Grenada
Grenada is an island country of the West Indies in the eastern Caribbean Sea. The southernmost of the Windward Islands, Grenada is directly south of Saint Vincent and the Grenadines and about north of Trinidad and Tobago, Trinidad and the So ...
.
See also
*
Reye syndrome
Reye syndrome is a rapidly worsening brain disease. Symptoms of Reye syndrome may include vomiting, personality changes, confusion, seizures, and loss of consciousness. While liver toxicity typically occurs in the syndrome, jaundice usually ...
*
Methylene cyclopropyl acetic acid
References
Toxic effect of noxious substances eaten as food
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