Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 1-year-old boy with a typical B12-responsive form of methylmalonic acidaemia was hospitalized twice due to acute bacterial infections. On both occasions, the child was lethargic with a severe ketoacidosis on admission. Intensive therapy with protein restriction, intravenous administration of electrolytes and antibiotics was effective within 4 days on both occasions. The urinary excretion of organic acids showed the same pattern on both occasions. There were rising excretion concentrations, reaching a peak value within the first 24-hour period, for the following compounds: 3-hydroxybutyric acid, 3-hydroxypropionic acid, 3-hydroxyisobutyric acid and 3-hydroxyisovaleric acid. Excretion concentrations of the following rose for 48 h: isobutyric acid, 2-methylbutyric acid, isovaleric acid, lactic acid and the 2-oxo-acids. There was no increase until 12-24 h after the onset of severe illness in the excretion of propionic acid and methylmalonic acid. Propionic acid excretion was maximal at about 48 h, while peak excretion of methylmalonic acid was delayed until about 72 h after the onset of severe illness; at this time there was clinical improvement. The biochemical implications of this excretion pattern are discussed.
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PMID:Excretion pattern of branched-chain amino acid metabolites during the course of acute infections in a patient with methylmalonic acidaemia. 677 38

A review is presented of 22 published cases of verified or probable mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency, a disorder of isoleucine and ketone body metabolism. The clinical expression, characterized by ketoacidosis, vomiting and lethargy, is highly variable. Typical age of onset is between 6 and 24 months. The disorder, which has been observed in several ethnic groups, is apparently inherited as an autosomal, recessive trait. The prognosis is relatively good if acute episodes of ketoacidosis and dehydration are adequately treated. There is abnormal urinary excretion of 2-methyl-3-hydroxybutyric acid, tiglylglycine, and in some instances also 2-methyl-acetoacetic acid. However, such a pattern of organic aciduria has also been found in cases with normal thiolase activity. Genetic complementation analyses have demonstrated considerable heterogeneity. The cDNA for human methyl-acetoacetyl-CoA thiolase has been cloned and sequenced. Studies in one patient showed a G-to-A substitution at position 1138 of the mRNA, causing 347Ala to Thr change in the mature enzyme. Studies in other patients have shown variable enzyme amount and/or stability.
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PMID:Mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency: an inborn error of isoleucine and ketone body metabolism. 848 3

A 71 year old hypertensive, non insulin-dependent diabetic patient with moderate renal insufficiency taking 500 mg/d of metformin and 5 mg/d of enalapril, developed metabolic acidosis characterized by fairly elevated anion gap, hyperchloremia, severe hyperkaliemia, normal plasma level of 3-hydroxybutyric acid, absence of ketonuria and high plasma level of lactic acid. This biochemical feature allowed us to ascribe the pathogenesis of metabolic acidosis, both to the increased plasma level of lactic acid and to the type IV renal tubular acidosis syndrome, the precipitating factor being an infection of urinary tract (as we assumed on the basis of the urine culture). The patient was dehydrated and lethargic; the ECG revealed the presence of nonparoxysmal junctional tachycardia. The clinical evolution was favorable under the treatment with an infusion of isotonic saline solutions, mild alkalinizing solutions, low-dose regular insulin and antibiotics. It is likely that metformin and enalapril, regularly taken by this nephropathic patient, could have played an iatrogenic role, even if the doses were low. This case highlights the importance of complying with the contraindications of these drugs, to avoid the rare but reported life-threatening complications of metformin administration.
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PMID:Possible synergistic effect of metformin and enalapril on the development of hyperkaliemic lactic acidosis. 948 83

Beta-ketothiolase deficiency is a rare autosomal recessive disorder characterized by an inborn error of isoleucine catabolism and affecting ketone body metabolism. Clinical features characterized by intermittent keto acidotic episodes are associated with clinical signs and symptoms of toxic encephalopathy such as lethargy, hypotonia, vomiting, tachypnea, and coma in some patients, with an onset during infancy or toddler-hood. A two months old girl presented to pediatric ward of Imam Reza Hospital in Mashhad City, Northwestern Iran in October 2016, with acute episode of fever and toxic encephalopathy with attack of vomiting, hypotonia, lethargy, tonic-clonic seizures and then a day in coma, few days after vaccination. After then similar episodes happened until 7 months age. Bio chemical tests that suggested diagnose of beta ketothiolase deficiency were attacks of ketoacidosis with urinary exertion of 2-methyl-3-hydroxybutyric acid 2-methyl aceto acetic acid tiglylglycine. In genetic assessment, we detected a novel homozygous mutation c.664A> C (p. Ser 222 Arg) in ACAT gene. This is the first report of beta ketothiolase deficiency confirmed by molecular analysis from Iran. We report on a homozygous variant in the ACAT1 gene and that is a novel mutation. We recommended carrier testing for all informative family members to recognize mutations in asymptomatic family members.
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PMID:A Novel Mutation of Beta-ketothiolase Deficiency: The First Report from Iran and Review of Literature. 3002 75