Survival after Treatment with Phenylacetate and Benzoate for Urea-Cycle Disorders

Enns, Gregory M.; Berry, Susan A.; Berry, Gerard T.; Rhead, William J.; Brusilow, Saul W.; Hamosh, Ada

doi:10.1056/nejmoa066596

Cited by 309 publications

(266 citation statements)

References 26 publications

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“…Lactic acidosis at admission is unusual in OTCD crises but may be explained in the present case by either an initial vasomotor instability related to brain edema or by transient ischemic brain damage, in accordance with the severity of this episode. The presence of a coma at admission was reported to be associated with a lower survival rate, particularly in OTCD patients (Enns et al 2007), and neurological symptoms persisted even after decreasing ammonemia levels under 100 mmol/L. In UCD, the function of excretion of nitrogen as urea is impaired and leads to accumulate ammonia and glutamine, two toxic molecules for the brain.…”

Section: Discussionmentioning

confidence: 99%

Intracranial Pressure Monitoring Demonstrates that Cerebral Edema Is Not Correlated to Hyperammonemia in a Child with Ornithine Transcarbamylase Deficiency

et al. 2015

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Background: Ornithine transcarbamylase deficiency (OTCD) is an inborn error of urea cycle resulting in increased plasma levels of ammonia and glutamine and cerebral edema. However, the underlying mechanism of brain cytotoxicity remains controversial. Our objective is to present an unusual acute hyperammonemic crisis suggesting a key role of brain glutamine to mediate ammonia neurotoxicity and the interest of intracerebral pressure (ICP) monitoring to maintain adequate cerebral perfusion pressure and to prevent neurological damages.Patient: A 6-year-old boy with OTCD was admitted for an acute hyperammonemic encephalopathy following viral infection. At admission, he presented vomiting, confusion, lethargy (Glasgow scale 7/15), and bilateral papilledema, suggesting cerebral edema. Plasma ammonia level was slightly increased (194 mmol/L, rr 25-50 mmol/L), contrasting with the severity of neurological deterioration and with high levels of glutamine in plasma (1,949 mmol/L, rr 335-666 mmol/L) and the brain (10-fold increase on in vivo MR spectroscopy). The patient was placed on neuroprotective treatments and respiratory support.Main Results: With a hypercaloric protein-free diet and nitrogen scavenger drugs, plasma levels of ammonia and glutamine rapidly decreased without neurological improvement. Continuous ICP monitoring showed repetitive peaks of pressure up to 60 mmHg in the first four days and was helpful to manage neuroprotective treatments. After several days, the patient progressively recovered without cognitive or motor disability.Conclusion: This case report highlights the discrepancy between the severity of neurological impairment, presumably related to high level of brain glutamine, and plasma levels of ammonia or glutamine in a child with acute hyperammonemic encephalopathy related to OTCD. In this situation, continuous ICP monitoring was helpful to manage neuroprotective treatments and prevent brain damages. Abbreviations CPPCerebral perfusion pressure ICP Intracranial pressure OTCD Ornithine transcarbamylase deficiency rr Reference range

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Section: Discussionmentioning

confidence: 99%

Intracranial Pressure Monitoring Demonstrates that Cerebral Edema Is Not Correlated to Hyperammonemia in a Child with Ornithine Transcarbamylase Deficiency

et al. 2015

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“…Patient-specific factors -when comparing pediatric patients with IEM with adults, it may be reasonable to assume that those patients who survive to adulthood have less severe disease and therefore are less likely to require a transplant for survival. While it is true that the survival rate of patients presenting over the age of 12 years with conditions like urea cycle defects and symptomatic hyperammonemia is much higher than those with earlier onset presentations (Enns et al 2007), mortality rate is high in patients with severe symptoms of an IEM regardless of age. For example, 25 % of female OTC patients who present with coma (Enns et al 2007) and 29 % of adults with acute presentations of MCAD (Lang 2009) will die.…”

Section: Discussionmentioning

confidence: 99%

“…While it is true that the survival rate of patients presenting over the age of 12 years with conditions like urea cycle defects and symptomatic hyperammonemia is much higher than those with earlier onset presentations (Enns et al 2007), mortality rate is high in patients with severe symptoms of an IEM regardless of age. For example, 25 % of female OTC patients who present with coma (Enns et al 2007) and 29 % of adults with acute presentations of MCAD (Lang 2009) will die. These publications (Enns et al 2007, Lang 2009) reflect a publication bias in that they focus on symptomatic cases and many adult patients with IEM such as MCAD will be asymptomatic.…”

Section: Discussionmentioning

confidence: 99%

“…For example, 25 % of female OTC patients who present with coma (Enns et al 2007) and 29 % of adults with acute presentations of MCAD (Lang 2009) will die. These publications (Enns et al 2007, Lang 2009) reflect a publication bias in that they focus on symptomatic cases and many adult patients with IEM such as MCAD will be asymptomatic. However, it is clear from these publications that adults with severe symptoms of their IEM may have poor outcomes.…”

Section: Discussionmentioning

confidence: 99%

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Barriers to Transplantation in Adults with Inborn Errors of Metabolism

Sirrs¹,

Faghfoury²,

Yoshida³

et al. 2012

JIMD Reports

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“…Algunos de ellos han sido empleados con éxito en pacientes con trastornos del ciclo de la urea (55), otros se han desarrollado específicamente para el tratamiento de la EH en pacientes con cirrosis hepática (56).…”

Section: Moduladores Del Metabolismo Del Amoniacounclassified