11/31. Late-onset presentation of ornithine transcarbamylase deficiency in a young woman with hyperammonemic coma.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.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
12/31. Acute extrapyramidal syndrome in mild ornithine transcarbamylase deficiency: metabolic stroke involving the caudate and putamen without metabolic decompensation.A 6-year-old male with partial ornithine transcarbamylase (OTC) deficiency had acute and rapidly progressive symmetrical swelling of the head of the caudate nuclei and putamina. Clinical presentation was ataxia and dysarthria progressing to seizures and coma; these symptoms gradually resolved with supportive management. Although he had been recently treated for mild hyperammonemia, there was no evidence of acute metabolic decompensation prior to presentation, and plasma ammonia and amino acids were consistent with good metabolic control. This case is novel in that the neurological insult affected the neostriatum of the basal ganglia and the episode occurred in the absence of an apparent metabolic abnormality, unique observations in a patient with OTC deficiency. CONCLUSION: This case suggests that the pathophysiology of metabolic stroke is complicated. It also argues for an evaluation for metabolic stroke in patients with known inborn errors of metabolism who present with unusual neurological symptoms in the absence of biochemical abnormalities. Similarly, this case suggests that patients presenting with unexplained neurological insults might benefit from an evaluation for an inborn error of metabolism.- - - - - - - - - - ranking = 1.2keywords = deficiency (Clic here for more details about this article) |
13/31. Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder.OBJECTIVE: Transplantation of isolated hepatocytes in animal models has been shown to correct inborn errors of metabolism. Based on these studies and our experience with hepatocyte transplantation in a child with crigler-najjar syndrome, isolated hepatocyte transplantation was performed to attempt metabolic reconstitution in a male infant with severe ornithine transcarbamylase (OTC) deficiency. methods: An infant with an antenatal diagnosis of OTC deficiency was managed intensively to prevent hyperammonemia. Isolated hepatocytes were obtained by collagenase perfusion of donated livers not used for transplantation. hepatocytes were infused in batches over the first 4 weeks of life via an umbilical venous catheter positioned in the portal vein. immunosuppression consisted of tacrolimus and corticosteroids. RESULTS: Over 4 billion viable hepatocytes were transplanted during the first 3.5 weeks of life. A period of metabolic stability was achieved between days 20 and 31 during which normal protein intake was tolerated while phenylbutyrate was weaned. During this time, plasma ammonia and glutamine remained within normal limits. hyperammonemia reappeared abruptly on day 31 of life. Protein tolerance diminished to baseline; metabolic stability was subsequently reattained only following successful liver transplantation at 6 months of age. CONCLUSIONS: Isolated hepatocyte transplantation appeared to result in temporary relief of hyperammonemia and protein intolerance attributable to OTC deficiency. The metabolic stability achieved was lost after 11 days presumably because of rejection of the transplanted cells because of insufficient immunosuppression. Future attempts at isolated hepatocyte transplantation for inborn errors of metabolism in humans should include adequate immunosuppression and a liver biopsy as a means of proving hepatocyte engraftment and function.- - - - - - - - - - ranking = 0.6keywords = deficiency (Clic here for more details about this article) |
14/31. brain MR imaging in neonatal hyperammonemic encephalopathy resulting from proximal urea cycle disorders.We present brain MR images in three patients with neonatal-onset hyperammonemic encephalopathy resulting from urea-cycle disorders (two sisters with deficiency of the carbamyl phosphate synthetase I reaction step and one boy with an ornithine transcarbamylase deficiency). MR imaging revealed almost identical findings of injury to the bilateral lentiform nuclei and the deep sulci of the insular and perirolandic regions; to our knowledge, this pattern has not been previously reported. We hypothesize that these lesions presumably reflect the distribution of brain injury due to hypoperfusion secondary to hyperammonemia and hyperglutaminemia in the neonatal period.- - - - - - - - - - ranking = 0.4keywords = deficiency (Clic here for more details about this article) |
15/31. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer.We report the death of an 18-year-old male with partial ornithine transcarbamylase (OTC) deficiency who participated in a pilot (safety) study of gene therapy. The vector used for this trial was based on human adenovirus type 5, deleted in E1 and E4, and contained human OTC cDNA. It was infused into the right hepatic artery at a dose of 6x10(11)particles/kg. Approximately 18 h. following gene transfer the subject was noted to have altered mental status and jaundice--clinical signs not seen in any of the first 17 subjects in this study. Subsequently, his clinical course was marked by systemic inflammatory response syndrome, biochemically detectable disseminated intravascular coagulation, and multiple organ system failure, leading to death 98 h following gene transfer. Post-mortem examination was consistent with the clinical course, and vector dna sequences were readily detectable in most tissues. The subject had high serum levels of IL-6 and IL-10 but normal TNFalpha immediately after infusion of the vector. This experience points to the limitations of animal studies in predicting human responses, the steep toxicity curve for replication defective adenovirus vectors, substantial subject-to-subject variation in host responses to systemically administered vectors, and the need for further study of the immune response to these vectors.- - - - - - - - - - ranking = 0.2keywords = deficiency (Clic here for more details about this article) |
16/31. Acute postpartum mental status change and coma caused by previously undiagnosed ornithine transcarbamylase deficiency.BACKGROUND: Acute postpartum mental status change usually represents postpartum blues or depression. Psychosis and coma are rare. This is a case report of a patient with previously undiagnosed ornithine transcarbamylase deficiency presenting as postpartum acute mental status change and coma. CASE: A 28-year-old multipara developed acute mental status change and coma 3 days after cesarean delivery. A metabolic profile and neurologic workup were unrevealing. An electroencephalogram revealed diffusely slow brain activity. She developed hyperammonemia and hyperglutaminemia and was diagnosed with ornithine transcarbamylase deficiency. Her newborn son was diagnosed with ornithine transcarbamylase deficiency on the previous day. Treatment with oral lactulose resulted in normalization of her ammonia level and resolution of her coma within 48 hours. She suffers no long-term sequelae. Dietary avoidance of protein was advised; outpatient treatment with sodium benzoate, sodium phenylacetate, and lactulose was initiated. A pedigree analysis is ongoing. CONCLUSION: Ornithine transcarbamylase deficiency should be included in the differential diagnosis of acute postpartum coma. hyperammonemia, hyperglutaminemia, and orotic aciduria are diagnostic, facilitate early treatment, and mitigate the risk of permanent neurologic impairment or death.- - - - - - - - - - ranking = 1.6keywords = deficiency (Clic here for more details about this article) |
17/31. Unusual causes of hyperammonemia in the ED.plasma ammonia measurement is a simple yet important screening in the ED for patients with unexplained stupor or delirium. Acute hyperammonemia is a medical emergency for which immediate steps must be taken to minimize permanent brain damage. Although the most common causes of hyperammonemia are severe abnormal liver function, the absence of liver disease in some cases has been observed. This brief report describes four hyperammonemia cases with normal liver function in the ED. On careful history and speculated examinations, ornithine carbamoyltransferase (OTC) deficiency, hematologic malignancy, and the side effects of valproic acid and 5-fluorouracil (5-FU) were considered. Therapy was first aimed at correcting the hyperammonemia. Once a specific diagnosis was reached, protein restriction, essential amino acid supplementation, efficient chemotherapy, and valproic acid and 5-FU level discontinuance were instituted. In this report, the clinical presentation, pathogenesis, and diagnostic workup for various hyperammonemia causes are discussed. Every EP should understand that the clinical symptoms for hyperammonemia and prognosis are related to early diagnosis.- - - - - - - - - - ranking = 0.2keywords = deficiency (Clic here for more details about this article) |
18/31. adult onset ornithine transcarbamylase deficiency: an unusual cause of semantic disorders.Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder. This condition usually presents in neonates or children. This report describes the clinical case of a 21 year old woman who was diagnosed in adulthood during the course of an unexplained coma. After recovery from the coma, she presented very unusual neuropsychological disorders involving memory and the meaning of certain words, suggesting a semantic deficit. The discovery of OTCD in adulthood is rare and the neuropsychological consequences may be unique.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
19/31. Fatal presentation of ornithine transcarbamylase deficiency in a 62-year-old man and family studies.Ornithine transcarbamylase deficiency (OTCD) resulting from deficiency of the mitochondrial enzyme OTC shows extensive phenotypic heterogeneity influenced by allelic heterogeneity and modifying environmental influences such as protein intake. We report the fatal late-onset presentation of OTCD in a 62-year-old man with the V337L mutation, a previous presentation in his grandson and negative clinical and biochemical screening of the proband's three daughters.- - - - - - - - - - ranking = 1.2226403865459keywords = deficiency, late-onset (Clic here for more details about this article) |
20/31. Intermittent hyperammonemic encephalopathy in a child with ornithine transcarbamylase deficiency.Ornithine transcarbamylase (OTC) deficiency is an X-linked disorder and the most common inherited cause of hyperammonemia. Clinical manifestations are more severe in hemizygous males who often present in neonatal period. Heterozygous females may be asymptomatic until juvenile or adulthood. Fluctuating concentration of ammonia, glutamine and other excitotoxic amino acids result in a chronic or episodically recurring encephalopathy. The authors report a heterozygous female with OTC deficiency who presented with recurrent encephalopathy.- - - - - - - - - - ranking = 1.2keywords = deficiency (Clic here for more details about this article) |
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