N-carbamylglutamate enhances ammonia detoxification in a patient with decompensated methylmalonic aciduria

Gebhardt, Boris; Vlaho, S; Fischer, Doris; Sewell, A. C.; Böhles, Hansjosef

doi:10.1016/s1096-7192(03)00095-7

Cited by 54 publications

(44 citation statements)

References 3 publications

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“…In this study, one out of four PA patients (patient A) did not initially respond to NCG. An insufficient NCG dose (75 mg/kg) may explain this finding, although one patient with organic aciduria responded to an initial dose of 70 mg/kg (Gebhardt et al 2003). Others reported initial doses ranging from 100 mg/kg to 250 mg/kg, all associated with reduction in ammonemia (Filippi et al 2010;Gebhardt et al 2003Gebhardt et al , 2005Jones et al 2008;Levrat et al 2008;Schwahn et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have suggested a role for NCG in the treatment of hyperammonemia in PA (Filippi et al 2010;Gebhardt et al 2003Gebhardt et al , 2005Jones et al 2008;Levrat et al 2008;Schwahn et al 2010). Since inhibition of N-acetylglutamate synthase may be a contributing factor to the hyperammonemia in PA, the use of NCG, a compound analogous to N-acetylglutamate, could stimulate CPSI in lieu of N-acetylglutamate (Hall et al 1958;Rubio and Grisolía 1981).…”

Section: Discussionmentioning

confidence: 99%

“…Other reports of use of NCG in PA are limited to the description of the trend of ammonia levels (Gebhardt et al 2003(Gebhardt et al , 2005Levrat et al 2008). Publication bias for successful NCG trials, various NCG doses, and concomitant dialysis and/or ammonia scavengers obscure the ability to draw accurate conclusions.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, N-carbamylglutamate (NCG), an analog of N-acetylglutamate, can activate CPSI, and NCG treatment has been shown to reduce hyperammonemia in initial, as well as subsequent, PA decompensation episodes (Filippi et al 2010;Gebhardt et al 2003Gebhardt et al , 2005Jones et al 2008;Levrat et al 2008;Schwahn et al 2010). Moreover, increased ureagenesis has been demonstrated in PA patients after administration of NCG (Ah Mew et al 2010).…”

Section: Introductionmentioning

confidence: 99%

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Short-Term Outcome of Propionic Aciduria Treated at Presentation with N-Carbamylglutamate: A Retrospective Review of Four Patients

et al. 2011

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N-carbamylglutamate (NCG) has been reported to decrease ammonia levels in patients with propionic aciduria (PA) and methylmalonic aciduria (MMA), but reports on clinical outcomes remain scant. Here, we report a retrospective series of four patients with neonatal PA treated with NCG at presentation. Patients presented between 2 and 9 days of age and peak plasma ammonia ranged from 524 to 1,572 mM. Patients received bolus (30-200 mg/kg) and sustaining (115-300 mg/kg per day) doses of NCG in addition to a standard treatment regimen that included ammonia scavenger drugs. Ammonia levels decreased significantly in three of the four cases within 2 h after administration of NCG and fell below 100 mM in all within 12-29 h. Two patients received NCG (bolus 200 mg/kg) while ammonia was above 500 mM (740 and 1,572) and their levels fell below 500 mM by 4 and 8 h post-treatment, respectively. Outcomes of these NGC-treated patients were not improved over previously reported PA patients who did not receive NCG: two died during the initial episode and one after his third metabolic decompensation at 46 days. The survivor is now 3 years old and has a well-controlled seizure disorder and a mild developmental delay mostly in language. We conclude that despite a trial of NCG and a rapid fall in plasma ammonia, the short-term outcome of these patients was not improved.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Short-Term Outcome of Propionic Aciduria Treated at Presentation with N-Carbamylglutamate: A Retrospective Review of Four Patients

et al. 2011

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“…Few recent reports exist on the use of NCG with conventional ammonia scavengers and dialysis for neonatal hyperammonaemia secondary to MMA [5,6,7]. There have been no trials to evaluate the effectiveness of using all these therapeutic treatments either singularly or in various combinations together with dietary manipulation.…”

Section: Introductionmentioning

confidence: 99%

N-Carbamylglutamate Is an Effective Treatment for Acute Neonatal Hyperammonaemia in a Patient with Methylmalonic Aciduria

Yap¹,

Leong²,

Aziz³

et al. 2016

Neonatology

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N-carbamylglutamate (NCG) has been used in combination with ammonia scavengers (sodium benzoate, sodium phenylbutyrate) and dialysis to treat hyperammonaemia in methylmalonic aciduria (MMA). The sole use of NCG for acute neonatal hyperammonaemia secondary to MMA is demonstrated in a neonate presenting at day 9 with encephalopathy, severe metabolic acidosis, hyperammonaemia (1,089 μmol/l), ketonuria and urinary methylmalonic acids. Emergency treatment included discontinuing protein feeds, providing high calories, carnitine and hydroxocobalamin. NCG 200 mg given at 0 and 90 min decreased plasma ammonia dramatically from 1,089 to 567 µmol/l at 90 min and further to 236 µmol/l at 6 h. Normalisation of ammonia was achieved at 12 h with two further doses of NCG 100 mg. This allowed for early re-institution of feeds at 14 h, followed by metabolic stabilization and recovery. Due to the effectiveness of NCG in this case, the use of the more invasive conventional ammonia-lowering therapeutic options could be avoided.

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Methylmalonic and propionic aciduria

Deodato

Boenzi

Santorelli

et al. 2006

American J of Med Genetics Pt C

237

186

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Methylmalonic and propionic aciduria (PA) are the most frequent forms of branched-chain organic acidurias. These autosomal recessive disorders result from deficient activity of methylmalonyl-CoA mutase and propionyl-CoA carboxylase, respectively. Clinically, acute or chronic neurologic signs are caused by the accumulation of toxic compounds proximal to the metabolic block. Phenotype varies from severe neonatal-onset forms with high mortality and poor outcome to milder forms with a later onset. In both cases the clinical course is dominated by the risk of relapses of life-threatening episodes of metabolic decompensation and of severe organ failure. Despite improvement of treatment, the overall outcome remains disappointing with no major differences between the two diseases. The diagnosis is based on the presence of characteristic compounds in body fluids as detected by organic acid analysis in urine and acylcarnitine profile in blood. Therapy is based on low-protein high-energy diet, carnitine supplementation, and metronidazole. Some patients with methylmalonic aciduria (MMA) respond to pharmacological doses of vitamin B12. Given the poor long-term prognosis, liver transplantation has been recently attempted as an alternative therapy to conventional medical treatment to cure the underlying metabolic defect. Nevertheless, the overall experience to date does not clearly demonstrate its effectiveness in preventing further deterioration or improving survival and quality of life. The recent implementation of neonatal screening by electrospray tandem mass spectrometry has decreased early mortality and improved the short-term outcome, without changing the detection rate of both diseases in the screening population compared to clinically detected cases. However, the limited number of patients and the short duration of their follow-up do not yet permit drawing final conclusions on its effect on the long-term outcome of methylmalonic and propionic acidemia.

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N-carbamylglutamate enhances ammonia detoxification in a patient with decompensated methylmalonic aciduria

Cited by 54 publications

References 3 publications

Short-Term Outcome of Propionic Aciduria Treated at Presentation with N-Carbamylglutamate: A Retrospective Review of Four Patients

Short-Term Outcome of Propionic Aciduria Treated at Presentation with N-Carbamylglutamate: A Retrospective Review of Four Patients

N-Carbamylglutamate Is an Effective Treatment for Acute Neonatal Hyperammonaemia in a Patient with Methylmalonic Aciduria

Methylmalonic and propionic aciduria

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