Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twin male infant siblings who presented in Harrow, UK, with a Reye's-like syndrome associated with profound hypoglycaemia, vomiting, diarrhoea, coma and death in one child, with dicarboxylic aciduria, and similarities to Jamacian vomiting sickness (hypoglycin toxicity) have been shown to excrete large amounts of a previously unrecorded urinary organic acid. This has been identified as 5-hydroxyhexanoic acid by gas chromatography mass spectrometry using a synthesized standard. Concentrations observed were 340 and 330 mg g-1 creatinine in the two patients. The metabolic precursor of the urinary acid is suggested to be hex-4-enoic acid, a probable chemical toxin closely related to the active organic acid metabolite of hypoglycin. The possibility of omega - 1 oxidation of hexanoic acid to 5-hydroxyhexanoic acid in these and other patients with dicarbocylic aciduris is also discussed.
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PMID:Identification of 5-hydroxyhexanoic acid in the urine of twin siblings with a Reye's-like syndrome associated with dicarboxylic aciduria and hypoglycaemia and with similarities to Jamaican vomiting sickness. 57 58

A number of inherited metabolic disorders are diagnosed by means of the nationwide newborn screening programme, usually before the first clinical signs occur. As for the rest of the varied metabolic disorders, knowledge and intuition of the paediatrician is a prerequisite for selection of patients for further metabolic investigation (selective screening procedure). Clinical symptoms of the most important metabolic diseases can be classified according to their pathophysiological background as: "intoxication type, energy deficiency type, storage type, neurodegenerative type". Especially in the first year of life, clinical features are unspecific: psychomotoric retardation, muscular hypotonia, cerebral convulsions, recurrent vomiting, sepsis-like conditions. In these cases indication for metabolic screening is broad. Especially in older children some clinical symptoms can be specific for a metabolic disorder: distinctive odour of urine, changes in hair, skin or eyes, organomegaly, skeletal changes. Recently, Reye-like syndrome, stridor, macrocephaly and vague, cerebral ischaemic episodes have been described in association with a metabolic defect. In conclusion, experience has shown that only a small number of metabolic disorders will be diagnosed from the typical clinical picture alone. In most cases a selective screening procedure leads to diagnosis because initial symptoms are unspecific.
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PMID:[Clinical suspicion of inborn errors of metabolism]. 141 7

Treatment of 17 children aged 2-9.5 years with a combination of pivmecillinam and pivampicillin (250-500 mumol 24 h-1) for more than 1 year resulted in a reduction of the free carnitine concentration in serum and muscle to less than 10% of the mean reference value. The decline in serum was slow, with an estimated half-life of about 5 months. Spontaneous replenishment occurred at about the same slow rate. Thus, there is no increase in endogenous carnitine synthesis as a response to increased demand of carnitine for detoxification. Supplementation with carnitine during treatment required at least a four-fold molar excess over pivalic acid to achieve and sustain a normal carnitine concentration. The replenishment of carnitine occurred with a half-life of 1.1-3.0 months. From determination of muscle-carnitine concentration in patients treated with pivaloyl-containing antibiotics and in patients with organic aciduris, we conclude that serum carnitine is a good predictor of carnitine stores in the body. Six non-supplemented patients with a serum free-carnitine concentration of 0.7-2.6 mumol l-1 had an inadequate ketone-body increase during a 24-h fast. Vomiting, nausea and tiredness occurred in three cases following the fasting period. After normalization of the serum-carnitine concentration, a normal response to fasting was observed. Thus, in some organic acidurias, for example medium-chain acyl-CoA dehydrogenase deficiency, a low liver concentration of carnitine may be an important contributing factor to hypoglycaemic and Reye-like attacks. We believe that prodrugs which contain pivalic acid should be avoided if acceptable alternatives exist. If used, supplementation with at least four-fold molar excess of carnitine is advisable.
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PMID:Effects of pivalic acid-containing prodrugs on carnitine homeostasis and on response to fasting in children. 151 15

An increasing number of reports indicate that patients with some inherited metabolic diseases may have symptoms resembling those of Reye's syndrome. We describe 2 patients who developed Reye-like syndrome at the age of 7 months respectively. Conscious disturbance, hepatomegaly, impaired liver function, hyperammonemia, and nonketotic hypoglycemia were noted during acute episode. Blood lactate level was normal in both cases. Liver and muscle biopsy of both patients showed macrovesicular fatty change. Increased density of matrix in hepatocyte mitochondria was noted in patient 1. Stacking of cristae was shown in patient 2. The first patient had another episode of hyperammonemia at 2 years of age. The second patient was admitted three more times due to recurrent vomiting and conscious change at the age of 7 months, 10 months and 13 months respectively. Fatty acid metabolic defect should be considered in children or infants with recurrent Reye-like syndrome.
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PMID:Recurrent acute encephalopathy due to fatty acid metabolic defect--report of two cases. 164 79

From 65 reported cases of medium chain acyl-CoA dehydrogenase deficiency, we found an average presenting age of 13.5 months and a mean age at death of 18.5 months. One quarter of patients died of a Reye-like syndrome and/or sudden infant death. In half the cases there had been at least one sibling death. Asymptomatic cases were not uncommon (12% of cases). The crises were generally induced by a prolonged fast and after a viral prodromal phase in three quarters of cases. The crises consisted of somnolence progressing to lethargy which could lead to coma. Vomiting was frequent (60% of cases). Seizures, which were found in 29% of cases, represented a bad prognosis. The physical examinations revealed frequently a variable and regressive anicteric hepatomegaly. Blood and urine analysis revealed in most instances hypoglycaemia (96% of cases) with hypoketonuria and sometimes metabolic acidosis. Hepatic and muscular cytolytic enzymes were frequently raised, as were plasma ammonia, urea, and uric acid. Plasma total or free carnitine concentrations, especially non-fasting, were diminished in most cases. Plasma saturated medium chain fatty acids and particularly unsaturated cis-4-decenoate were on the other hand raised during the crises or during fasting. Urinary organic acid analysis revealed a characteristic profile of medium chain aciduria: C6-C10 dicarboxylic acids, hydroxy acids, glycine conjugates, and carnitine conjugates. Oral loading tests with carnitine or phenylpropionate allow a precise diagnosis. The diagnosis is confirmed by specific assays in various tissues. Avoidance of prolonged fasting seems to be the mainstay of treatment.
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PMID:Medium chain acyl-CoA dehydrogenase deficiency. 173 32

Serum NEFA profiles in Reye's syndrome are reportedly unique with a disproportionate percent made up of polyunsaturated fatty acids some of which are not ordinarily found in the serum. This pattern is also reflected in the serum triglyceride composition as well. As the liver is probably the sole source of the serum triglyceride in Rye's syndrome because patients are vomiting or in coma, the fatty acid acid composition of the liver triglyceride was examined for insight regarding the lipid abnormalities in this disease. Palmitic acid (16:0) and the sum of all the saturated fatty acids in the liver triglycerides were significantly decreased whereas the sum of the monoenoic fatty acids and the products of delta 9 desaturase activity were increased in Reye's samples. When these data were compared to the fatty acid composition of the serum triglyceride from a separate cohort of Reye's and control subjects, certain inferences regarding hepatic delta 9, delta 6, delta 5, and delta 4 desaturase activities and the elongases can be drawn from the liver and serum triglyceride fatty acid profiles which are unique. Collectively, these data reflect considerable intrahepatic fatty acid desaturation and elongation activity and/or acyl transfer from lipid to lipid of various polyunsaturated fatty acids in Reye's syndrome.
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PMID:Fatty acid composition of hepatic triglycerides in Reye's syndrome: implications for hepatic desaturase abnormalities. 181 59

An outbreak of food poisoning resulting in 13 deaths in children occurred in Malaysia during the Chinese Festival of the Nine-Emperor Gods in 1988. The offending food was a Chinese noodle called 'Loh See Fun' (LSF). The source was traced to a factory where a banned food preservative was added to make the LSF. The food poisoning was attributable to aflatoxins and boric acid. The clinical features included vomiting, pyrexia, diarrhoea, abdominal pain, anorexia, giddiness, seizures, and eventual coma. Initially, many presented with a Reye-like syndrome. Eleven post-mortem examinations were performed. The pathological findings included extensive coagulative necrosis of the liver with proliferative 'ductal/ductular metaplasia of the hepatocytes'. Giant cell formation, central vein sclerosis, bile stasis, and steatosis were also noted. There was presence of acute tubular necrosis, superficial upper gastrointestinal erosions, and ensuing encephalopathy. The eventual cause of death is acute hepatic and renal failure.
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PMID:An outbreak of aflatoxicosis and boric acid poisoning in Malaysia: a clinicopathological study. 189 May 47

Serum salicylate concentration was measured at admission in 130 children with liver-biopsy-confirmed Reye's disease. Mean serum salicylate was 12.3 mg/dl and mean salicylate concentrations by neurological grade (Lovejoy) were: stage I, 12, stage II, 13, stage III, 11, stage IV, 13, and stage V, 13 mg/dl. However, mean serum salicylate (15 mg/dl) at admission in 21 patients who died or had serious neurological deficits was significantly higher than that in 103 patients who survived without neurological sequelae (10 mg/dl). Serum salicylate in a group of 27 age-matched, community-matched control children collected consecutively over the period 1978-80 was less than 2 mg/dl, and children with varicella or influenza had salicylate concentrations indistinguishable from apparently well classmates or siblings. It is impossible to determine from this data whether salicylates are involved in the aetiology of or in determining the outcome of Reye's disease. Increased concentrations of salicylates at admission could be the result of excessive dosage because of a greater severity of the prodromal illness, or to diminished excretion because of impaired hepatic metabolism. It seems likely that serum salicylate concentrations entered the toxic range in many patients with Reye's disease before they presented for treatment. Most had been vomiting and had diminished oral intake for 33-55 h before hospital admission. Since the average number of hours from the beginning of vomiting to admission was no different in non-comatose and comatose cases, the time at which salicylate concentration was measured in relation to the last dose was probably similar in the two groups and therefore does not account for the higher levels in children with poor outcome. Salicylates are mitochondrial toxins and mitochondria are known to be significantly injured in Reye's disease; therefore, it seems wise to avoid the use of aspirin in children during outbreaks of Reye's disease.
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PMID:Serum salicylate concentrations in Reye's disease. A study of 130 biopsy-proven cases. 611 59

Medium chain acyl-CoA dehydrogenase deficiency (MCAD) is a defect in the mitochondrial oxidation of fatty acids. The disorder typically presents with episodes of vomiting and hypoglycemia, sometimes with changes in mental status and hepatic failure. These Reye's-like features may culminate in coma and death. Stress, intercurrent illness, and reaction to childhood immunization have been shown to precipitate acute metabolic episodes in MCAD patients. All cases are caused by mutations of the single MCAD gene on chromosome 1. Most clinically ascertained cases are caused by an A985G transition in exon 11. Here we report the preliminary findings of MCAD patients detected prospectively through a supplemental newborn screening program in Pennsylvania using tandem mass spectrometry. From the first 80,371 newborns screened we prospectively found nine babies with MCAD (1/8930) plus two additional newborns screened because of a previously known family history. Molecular analysis showed 56% of the detected patients to be compound heterozygotes for the A985G and a second mutation. This is in contrast to clinical retrospective studies which have found only 20% to be compound heterozygotes. We have identified two of the other mutations including a novel mutation (DG91/C92, 6-bp deletion) in one of our patients by using single-stranded conformation polymorphism (SSCP) and sequence analysis of conformers. Our results confirm that MCAD is one of the more common inborn errors of metabolism. The different mutation frequencies observed between retrospective clinical studies and our prospective newborn screening study suggest that clinical ascertainment may lead to preferential identification of the A985G mutation.
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PMID:Medium chain acyl-CoA dehydrogenase deficiency in Pennsylvania: neonatal screening shows high incidence and unexpected mutation frequencies. 760 90

A 9-year-old girl was referred to our hospital after recurrent episodes of hypoglycemia, altered consciousness and persistent vomiting without acetonemia or myopathic symptoms. Other pertinent laboratory data included elevated BUN, hyperammonemia and very low levels of triglycerides with elevated free fatty acids. The patient was born from unaffected but related parents (second cousins) and the illness was previously diagnosed as Reye encephalopathy. Recurrence of similar attacks suggested an underlying metabolic disorder. Several syndromes of impaired FFA beta oxidation were taken into account and discarded successively after laboratory investigations: systemic carnitine deficiency, Medium and Long Chain Acyl-CoA Dehydrogenase deficiency and Multiple Acyl CoA Dehydrogenation deficiency (Glutaric aciduria, Ethylmalonic-adipic aciduria and riboflavin-responsive multiple acyl CoA dehydrogenation deficiency). Urinary and hematic gas-chromatography and Mass-Spectrometry show no abnormality in Medium Chain fatty acids and in C6-C10 dicarboxylic acids. Carnitine plasma concentrations (both total and free) were above normal levels while in urine acetyl carnitine was low in respect to longer acyclic radicals. Among metabolic defects located at the level of hepatic fatty acid oxidation, only Carnitine Transferase deficiency can explain this peculiar mosaic of data (precursors of the blocked reaction are elevated in blood whereas lack of the metabolites derived uniquely from this reaction explains all the clinical manifestations).
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PMID:[Non-ketotic hypoglycemia caused by carnitine palmitoyl transferase 1 deficiency]. 848 29


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