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)

Medium-chain acyl-CoA dehydrogenase deficiency is a recently described inborn error of metabolism characterized by episodes of coma and hypoketotic hypoglycaemia in response to prolonged fasting. Secondary carnitine deficiency has been documented in these patients as well as the excretion in the urine of medium-chain-length acyl carnitine esters, such as octanoylcarnitine. Based on the potential toxicity of medium-chain fatty acid metabolites and the beneficial responses of patients with other inborn errors of metabolism and secondary carnitine deficiency, oral carnitine has been proposed as treatment for children with medium-chain acyl-CoA dehydrogenase deficiency. We report the results of carefully monitored fasting challenges of an infant with this deficiency both before and after 3 months of oral carnitine therapy. Carnitine supplementation failed to prevent lethargy, vomiting, hypoglycaemia and accumulation of free fatty acids in response to fasting despite normalization of plasma carnitine levels and a marked increase in urinary excretion of acyl-carnitine esters. Potentially toxic medium-chain fatty acids accumulated in the plasma in spite of therapy. Based on this study of one patient, we stress that avoidance of fasting and prompt institution of glucose supplementation in situations when oral intake is interrupted remain the mainstays of therapy for medium-chain acyl-CoA dehydrogenase deficient patients.
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PMID:Medium-chain acyl-CoA dehydrogenase deficiency: metabolic effects and therapeutic efficacy of long-term L-carnitine supplementation. 250 71

Two patients requiring total parenteral nutrition for 34 and 39 months, had plasma and urinary carnitine assays and plasma lipid assays performed before and during intravenous administration of 400 mg (2500 mumol) of L-carnitine for 7 days, followed by 40 mg (240 mumol) daily continuously. One patient had generalized lethargy and weakness which resolved within the first 5 days of carnitine administration. The plasma-free carnitine levels in this patient rose significantly. The other patient was asymptomatic and while there was no significant change in the plasma-free carnitine levels during carnitine administration, this patient remained in positive carnitine balance throughout the study. There were no significant changes in plasma lipid levels in either patient. In adult patients requiring long-term total parenteral nutrition who are otherwise normal, intravenous L-carnitine may be required to supplement the patients endogenous carnitine production.
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PMID:Carnitine balance and effects of intravenous L-carnitine in two patients receiving long-term total parenteral nutrition. 644 Oct 18

A 12-year old boy suffered episodes of vomiting, lethargy, and hypoglycaemia from the age of 1 year. Adhering to a vegetarian diet caused an increase in frequency and severity of the attacks. It was found that he was suffering from systemic carnitine deficiency that responded promptly to treatment with L-carnitine.
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PMID:Systemic carnitine deficiency exacerbated by a strict vegetarian diet. 670 71

We present five cases of children with severe neurologic handicaps whose management was complicated by excessive lethargy. Treatment with L-carnitine in a dosage range of 35-50 mg/kg/day resulted in a marked improvement in alertness and arousability. In four cases, when L-carnitine was discontinued for a month, they all promptly became lethargic. When L-carnitine was re-started, the lethargy resolved and the improvement has been maintained for up to 14 months. In three children who were tested, serum carnitine levels (total and free) were normal before starting L-carnitine treatment.
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PMID:L-carnitine as a treatment of lethargy in children with chronic neurologic handicaps. 804 4

A 17-year-old girl with Rett syndrome, who was taking no other medications, was treated with L-carnitine (50 mg/kg/day). Within 2 months of initiation of treatment, she became much more alert, developed good eye contact, started reaching for objects with both hands, and answered simple questions with one or two words. L-carnitine was discontinued and within 1 week she lapsed into her pretreatment condition of lethargy with no interest in her environment, not reaching for objects, poor eye contact, and not speaking. One week after L-carnitine was resumed, she again became alert, started reaching for objects, and saying one or two words. Her serum carnitine levels (free and total) were within normal limits before and after L-carnitine treatment, but were higher while she was taking L-carnitine. Her serum ammonia was within normal limits prior to starting L-carnitine. L-carnitine appears to be an effective treatment for this girl with advanced Rett syndrome.
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PMID:L-carnitine as a treatment for Rett syndrome. 827 24

A 3-year-old boy had recurrent episodes of lethargy, encephalopathy, and hepatomegaly accompanied by hypoglycemia, elevated liver aminotransferase and creatine kinase values, and nonketotic dicarboxylic aciduria; the serum carnitine level was moderately reduced. Carnitine palmitoyltransferase II activity was decreased in lymphocytes and fibroblasts. Therapy with L-carnitine and a diet low in long-chain triglycerides did not prevent recurrent episodes.
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PMID:Recurrent metabolic decompensation in profound carnitine palmitoyltransferase II deficiency. 828 68

Carnitine is a small water-soluble molecule that is present in almost all animal species. It plays an indispensable role in fatty acid metabolism, where it is involved in the transport of activated fatty acids between different cellular compartments. Uremic patients, as well as patients with chronic renal failure, appear to have abnormal renal handling of carnitine leading to dyslipidemia, lethargy, muscular weakness, hypotension, cardiac dysfunction and arrhythmias, and recurrent cramps. It often is difficult to distinguish these symptoms from similar ones related to uremia and dialysis. Many investigators have advocated L-carnitine supplementation in an attempt to alleviate carnitine deficiencies, and good results from this therapy have been reported. Moreover, several studies have shown that L-carnitine supplementation improves the response to erythropoietin. Chronic inflammation is another particular aspect affecting these patients. Anti-inflammatory properties of L-carnitine in hemodialysis patients have been shown by our group. Treatment with L-carnitine (20 mg/kg, given intravenously at the end of each dialysis session for 6 mo), significantly decreased serum C-reactive protein (CRP) levels, a proinflammatory cytokine known to inhibit erythropoiesis. Moreover, data from published literature are indicative of L-carnitine modulation of the immune system by the activation of glucocorticoid receptors and the modulation of the transcription of glucocorticoid-responsive genes. Our study showed that in these patients, treatment with L-carnitine has been able to improve their body mass index, likely by promoting a positive protein balance. This aspect is strictly correlated with the status of insulin resistance, which is well described in patients with renal diseases. Many studies showed that carnitine allowed mitochondrial fatty acid usage to link to the rate of glucose usage, thus improving insulin resistance. In conclusion, clinical beneficial effects of L-carnitine treatment on patients suffering from renal diseases are supported by molecular evidence involving both inflammatory and metabolic aspects of the disease.
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PMID:Carnitine system in uremic patients: molecular and clinical aspects. 1549 Apr 12

A 12-month-old boy diagnosed with propionic acidemia underwent gastrostomy. The patient's general state was good and he was alert, but with reduced muscular tone (unstable when seated with support, floppy head) and with dystonic movements in all extremities. An electroencephalogram showed slightly slowed brain activity. The patient was being treated with a low protein diet, phenobarbital, L-carnitine, L-isoleucine, and biotin. Surgery was carried out in satisfactory conditions with general anesthesia without opioids combined with infiltration of the surgical wound with local anesthetic. Recovery from anesthesia was rapid and free of complications. Propionic acidemia is caused by mitochondrial propionyl coenzyme carboxylase deficiency. Most patients have episodes of severe metabolic ketoacidosis as a result of excessive protein intake, delayed development, vomiting, gastroesophageal reflux, lethargy, hypotonia, and convulsions. The anesthetic approach involves avoiding triggers of metabolic acidosis (such as fasting, dehydration, hypoxemia, and hypotension) and preventing airway complications. Agents that metabolize propionic acid (such as succinylcholine, benzylisoquinoline neuromuscular blocking agents, and propofol) are not used, as they can exacerbate acidemia. We also believe that using local or regional anesthesia in combination with general anesthesia without opiates is safe and effective for controlling pain during surgery and postoperative recovery, as that combination avoids respiratory depression in these patients, who are highly sensitive to opiates.
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PMID:[Infant boy with propionic acidemia: anesthetic implications]. 1620 Sep 24

Withdrawal from psychostimulants, including methamphetamine, induces a depressive state associated with lethargy, dysphoria, hyperphagia and psychomotor retardation. Previous work with repeated administration of amphetamine in rats has shown that amphetamine withdrawal produces decreased motivation to work for a non-drug reward, and this withdrawal is reversed by administration of a dopamine partial agonist. The purpose of the present study was to examine decreased motivation to work for a non-drug reward during methamphetamine withdrawal and explore the effects of a dopamine agonist, dopamine partial agonist, and indirect monoamine agonist on methamphetamine withdrawal. During withdrawal from repeated methamphetamine administration, rats showed reduced responding for a sweet solution in a progressive-ratio schedule of reinforcement, and this effect was significantly more pronounced than previously observed with amphetamine. Repeated systemic treatment with the dopamine partial agonist terguride (0.2 and 0.4 mg/kg, i.p., twice daily), the full dopamine agonist ropinirole (1 mg/kg, i.p., twice daily), and acetyl-L-carnitine (60 and 100 mg/kg, i.p.), a compound with a potential antidepressant effect, during methamphetamine withdrawal restored responding for the sweet solution, suggesting that these drugs may represent potential therapeutic strategies for the treatment of methamphetamine addiction during the withdrawal phase.
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PMID:Effects of terguride, ropinirole, and acetyl-L-carnitine on methamphetamine withdrawal in the rat. 1664 7

Valproic acid (VPA) is used to manage a variety of conditions, including simple and complex absence seizure disorder, bipolar disorder, and migraine prophylaxis. The clinical manifestations of VPA overdose range in severity from mild confusion and lethargy to severe coma and death. The treatment of VPA toxicity is mainly supportive. There is no specific antidote or guidelines for managing VPA intoxication. Anecdotal reports describe the efficacy of naloxone and L-carnitine, but the data are insufficient to make strong conclusions. Various extracorporeal techniques for managing VPA toxicity have been described, but none has prevailed as standard therapy. We report a patient with VPA overdose who was treated successfully with hemoperfusion with activated charcoal and L-carnitine. The VPA level of the patient exceeded 1000 microg/mL and was normalized after 3 rounds of hemoperfusion. The patient was injected with L-carnitine at a maximum of 600 mg/kg per day for 5 days without complications.
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PMID:A case of hemoperfusion and L-carnitine management in valproic acid overdose. 1835 83


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