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)

We reviewed the natural history and differential diagnosis of ornithine transcarbamylase deficiency (an X-linked inborn error of urea synthesis) in 13 symptomatic female heterozygotes. The patients presented as early as the first week of life or as late as the sixth year. The most common symptoms before diagnosis were nonspecific: episodic extreme irritability (100 percent), episodic vomiting and lethargy (100 percent), protein avoidance (92 percent), ataxia (77 percent), Stage II coma (46 percent), delayed physical growth (38 percent), developmental delay (38 percent), and seizures (23 percent). Including the proband, 42 percent of the female members of the 13 families studied had symptoms. The median interval between the onset of major symptoms (vomiting and lethargy, seizures, and coma) and diagnosis was 16 months (range, 1 to 142). Five patients had IQ scores below 70 at the time of diagnosis. We suggest that careful evaluation of the family history, the dietary history, the episodic nature of the nonspecific symptoms, the response of these symptoms to the withdrawal of protein, and their frequent onset at the time of weaning from breast milk will permit early diagnosis and might thereby reduce the risk of death or neurologic impairment in female patients with partial ornithine transcarbamylase deficiency.
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PMID:Natural history of symptomatic partial ornithine transcarbamylase deficiency. 394 92

Ornithine transcarbamylase deficiency is an X-linked recessive disorder of urea biosynthesis characterized by recurrent, often fatal, hyperammonemic encephalopathy in affected males; carrier females are usually asymptomatic. We report here the clinical and laboratory findings in five symptomatic heterozygous females with ornithine transcarbamylase deficiency. In each case, the onset of symptoms occurred in the 1st year of life, but diagnosis was delayed by up to 15 years. Symptoms included recurrent vomiting with lethargy (five patients), dietary protein intolerance (five), irritability (four), severe acute encephalopathy (three), ataxia (three), and acute hemiparesis (two). All eventually showed evidence of developmental delay or learning difficulties. Two of the three who experienced severe, acute, hyperammonemic encephalopathy suffered serious, permanent neurologic sequelae. Three of the patients showed decreased ornithine transcarbamylase activity in liver obtained by needle biopsy, and the other two had marked orotic aciduria associated with hyperammonemia. Neuroimaging studies demonstrated persistent abnormal lobar attenuation and abnormal signal on computed tomographic scan and magnetic resonance imaging. All patients showed marked symptomatic improvement on treatment with dietary protein restriction supplemented by pharmacologic measures to increase nonprotein nitrogen excretion. Ornithine transcarbamylase deficiency should be considered in the differential diagnosis of acute or chronic encephalopathy in females at any age.
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PMID:Ornithine transcarbamylase deficiency in females: an often overlooked cause of treatable encephalopathy. 749 56

Ornithine transcarbamylase deficiency (OTCD) is caused by an alteration of urea synthesis, linked with partial modification of the X-chromosome, whose clinical manifestations are: lethargy, nausea, vomiting and cerebral edema. While in newborn males OTCD presents with hyperammoniemia leading to cerebral palsy with profound neurological impairment and eventually death, in women who are healthy carriers, it is possible to detect the disorder only through specific tests, since heterozygote women are rarely symptomatic. We describe the case of a young woman admitted to the hospital after an episode of mental confusion with vomiting and psychomotor restlessness, which had previously occurred several times during the premenstruum and lasted a few hours. A 2 day history of stupor made admission mandatory. Tests carried out during the hospital stay showed marked hyperammoniemia and unconjugated hyperbilirubinemia, marked cerebral edema documented by a CT scan. Liver biopsy and CSF test were normal. Screening of plasma and urinary aminoacids, level of orotic acid in the urine and OTC activity in the liver, confirmed the diagnosis of OTCD. The possibility of early diagnosis and therapy of a disease which otherwise leads to death, emphasizes the importance of precise evaluation of a possible organic cause of anorexia and behaviour disorders in young women.
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PMID:Hyperammoniemic coma in an adolescent girl: an unusual case of ornithine transcarbamylase deficiency. 828 23

Urea Cycle Disorders (UCD) is an inborn error of urea synthesis in which ammonium and other nitrogenous precursors of urea accumulate leading to episodic coma and a high mortality rate. Therapy with peritoneal dialysis, essential amino acids or their nitrogen-free analogues has increased survival. The authors report 5 cases of urea cycle disorders, all of whom developed and were rescued from hyperammonemic coma. However, the eventual outcome was quite variable. Argininosuccinate lyase deficiency (ALD) Case 1. A 2 month old male infant, a product of a consanguineous marriage (Suphanburi province); developed poor feeding on day 7, lethargy, convulsion, hepatomegaly and respiratory alkalosis leading to respiratory failure and coma. Hyperammonemia, elevation of glutamic acid and argininosuccinic acid and its anhydrides confirmed the diagnosis of ALD. He is now 9 years old and severely retarded. Case 2. A male infant with history of lethargy, poor feeding on day 3, treated as sepsis and required respiratory support for 6 days; subsequently readmitted at age 2 weeks with vomitting, lethargy, seizure activity and hyperammonemia, and was treated by a local pediatrician in Songkhla province. There was a history of parental consanguinity and he was referred to Siriraj Hospital on day 64 with severe essential amino acid deficiency and acrodermatitis enteropathica with markedly elevated plasma citrulline level. In spite of aggressive treatment; the patient developed sepsis and he expired on day 78. Ornithine transcarbamylase deficiency (OTC) Case 3. An eleven-month-old male infant, the product of a non-consanguineous marriage, developed neonatal onset of hyperammonemia on day 5 after poor feeding, lethargy, hypothermia, seizure, apnea and coma. He was rescued from neonatal hyperammonemic coma on day 9 after aggressive treatment, but expired at eleven months of age after overwhelming sepsis. Case 4. A male infant, sibling of case 3 was referred to Siriraj Hospital on day 8 with hyperammonemia and coma. In spite of intensive genetic counseling given after the birth of their first child with OTC, the couple chose to have another baby without informing any physician. The baby developed vomiting and lethargy on day 2; subsequently hyperammonemia was noted. In spite of aggressive treatment given; hepatic dysfunction, renal failure and disseminated intravascular coagulation defects occurred on day 15. He expired on day 18 after parental permission for discontinuation of all treatment. Argininosuccinate synthetase deficiency (ASS) or Citrullinemia. Case 5. A seven week old female infant, the product of a consanguineous marriage and of Pakistani ethnic origin; developed intermittent vomiting from day 6. Initial diagnoses included ruminations, sepsis and pyloric stenosis for which she was operated on (day 30); however, vomiting continued; subsequently seizures, hyperammonemic coma developed and she was rescued from hyperammonemic coma within 30 hours. Significant elevations of citrulline and L-glutamine were demonstrated. She was discharged in excellent condition to her home in Dubai, the United Arab Emirates.
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PMID:Urea cycle disorders in Thai infants: a report of 5 cases. 1240 52

Ornithine transcarbamylase deficiency (OTCD) is an X-linked inherited disease and the most common inborn error in urea synthesis in human patients. In adult heterozygous patients, OTCD can be responsible for life-threatening hyperammonemic coma. We report the case of a 32-year-old woman admitted to our hospital with seizures after a recent high protein load. Her parents related a history of recurrent episodes of vomiting, meat refusal, lethargy, and convulsions since childhood, and measurement of plasma ammonemia levels was the key to early diagnosis of OTCD. We report the pathophysiologic characteristics, clinical features, clinical course, and differential diagnosis of OTCD and discuss the therapeutic options, including continuous venovenous hemodiafiltration and pharmacologic therapy for reduction of plasma ammonemia levels. A diagnosis of OTCD should be considered in adult nonhepatic patients with hyperammonemic coma, particularly if they have a history of protein avoidance and neurologic symptoms. Early recognition and appropriate treatment are critical to avoid severe brain damage and death.
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PMID:Late-onset presentation of ornithine transcarbamylase deficiency in a young woman with hyperammonemic coma. 1251 90

OBJECTIVE: To drive pediatrician's attention to a urea cycle enzyme deficiency. The prognosis is directly related to the early diagnosis and treatment. METHODS: We describe a newborn patient who present lethargy, vomitus and seizures 48 hours afther birth. We investigated this patient and the diagnosis of ornithine transcarbamylase deficiency was made. Treatment was started immediately. RESULTS: We followed the patient until he was 1 year old, when he had liver transplant with a good outcome of the disease. CONCLUSION: The ornithine transcarbamylase deficiency is a rare and very serious disease. Any newborn whose evolution is similar to that of a septic patient without any infection must be investigated for this disease. The prognosis is directly related to the early diagnosis and treatment.
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PMID:[Ornithine transcarbamylase deficiency: neonatal diagnostic] 1468 53

We report the case of a 7-year-old girl with ornithine transcarbamylase deficiency whose quality of life (QOL) improved greatly after a living donor liver transplantation (LDLT). Ornithine transcarbamylase deficiency had been diagnosed when she was 2 years old and she finally underwent LDLT, with her father as the donor, when she was 7 years old. The patient had suffered episodes of hyperammonemic encephalopathy ranging from lethargy to coma, treated by hemodialysis twice before LDLT, and her intelligence quotient was borderline for her age. Preoperative magnetic resonance imaging (MRI) showed an atrophic area in the subcortical white matter of the frontal lobe. After LDLT, the patient suffered acute rejection with hyperamylasemia, but not hyperammonemia. Postoperative MRI and quantitative MR spectroscopy showed no changes in the subcortical lesion. She has been followed up carefully for 16 months and has had no further complications or any sign of hyperammonemia.
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PMID:Improved quality of life and unchanged magnetic resonance brain imaging after living donor liver transplantation for late-onset ornithine transcarbamylase deficiency: report of a case. 1634 94

Valproate-induced hyperammonemic encephalopathy (VHE) is an unusual complication characterized by a decreasing level of consciousness, focal neurological deficits, cognitive slowing, vomiting, drowsiness, and lethargy. We have thoroughly reviewed the predisposing factors and their screening, the biochemical and physiopathological mechanisms involved, the different treatments described, and those that are being investigated. Etiopathogenesis is not completely understood, although hyperammonemia has been postulated as the main cause of the clinical syndrome. The increase in serum ammonium level is due to several mechanisms, the most important one appearing to be the inhibition of carbamoylphosphate synthetase-I, the enzyme that begins the urea cycle. Polytherapy with several drugs, such as phenobarbital and topiramate, seems to contribute to hyperammonemia. Hyperammonemia leads to an increase in the glutamine level in the brain, which produces astrocyte swelling and cerebral edema. There are several studies that suggest that treatment with supplements of carnitine can lead to an early favorable clinical response due to the probable carnitine deficiency induced by a valproate (VPA) treatment. Development of the progressive confusional syndrome, associated with an increase in seizure frequency after VPA treatment onset, obliges us to rule out VHE by screening for blood ammonium levels and the existence of urea cycle enzyme deficiency, such as ornithine carbamoyltransferase deficiency. Electroencephalography (EEG) is characterized by signs of severe encephalopathy with continuous generalized slowing, a predominance of theta and delta activity, occasional bursts of frontal intermittent rhythmic delta activity, and triphasic waves. These EEG findings, as well as clinical manifestations and hyperammonemia, tend to normalize after VPA withdrawal.
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PMID:Valproate-induced hyperammonemic encephalopathy. 1677 19

Ornithine transcarbamylase deficiency is the most common inherited urea cycle disorder. Its clinical manifestations as lethargy, vomites, coma and cerebral edema are the effect of the higher concentration of the ammonia in plasma. Hyperammonemia, caused by mutation in ornithine transcarbamylase gene, is often considered as a reason of coma by pediatricians but skipped by internist, although it is the third reason of hepatic coma in adults. This article is the recapitulation of published studies and their implication on everyday clinical practice.
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PMID:[Hyperammonemia type II as an example of urea cycle disorder]. 1720 50

The urea cycle is the major metabolic pathway for excretion of waste nitrogen. Ornithine transcarbamylase deficiency is the most frequent urea cycle disorder. It is a hereditary-X-linked disease with over 150 mutations described. Ornithine transcarbamylase deficiency causes vomiting, lethargy, hyperventilation, and even death, mainly in the neonatal period. Ammonia, an extremely toxic molecule for the organism, is generated during protein catabolism and is accumulated in patients with this deficiency. Part of the treatment consists of a low-protein diet, to avoid hyperammonemia episodes, which can even have a fatal outcome. Patients can become deficient in several amino acids, either through the low-protein diet or directly through the primary enzyme deficiency; this in turn can cause an acrodermatitis enteropathica-like dermatosis.
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PMID:Acrodermatitis enteropathica-like dermatosis associated with ornithine transcarbamylase deficiency. 1784 64


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