<i>N</i>‐Carbamylglutamate protects patients with decompensated propionicaciduria from hyperammonaemia

Gebhardt, Boris; Dittrich, S; Parbel, S; Vlaho, S; Matsika, O; Böhles, Hansjosef

doi:10.1007/s10545-005-5260-7

Cited by 66 publications

(49 citation statements)

References 7 publications

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“…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). One reported patient had no response to a dose of 25 mg/kg (Jones et al 2008).…”

Section: Discussionmentioning

confidence: 96%

“…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%

“…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: 96%

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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“…Gebhardt et al described two patients with PA and hyperammonaemia who were treated with N-carbamylglutamate (NCG), an analog of N-acetylglutamate. Their blood ammonia levels were decreased even by first dose of NCG and normalized in a 6-h period (Gebhardt et al 2005). Since then, other cases of hyperammonaemia secondary to PA treated with NCG have …”

Section: Discussionmentioning

confidence: 97%

Nutritional and Pharmacological Management during Chemotherapy in a Patient with Propionic Acidaemia and Rhabdomyosarcoma Botryoides

et al. 2012

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We present the nutritional and pharmacological management of a 2-year-old girl with a severe form of propionic acidaemia and a genitourinary embryonal rhabdomyosarcoma. This association has not been described before, nor the utilization of chemotherapy in patients with propionic acidaemia.The patient is a girl with neonatal onset of propionic acidaemia, homozygous for the c.2041-2924del3889 mutation in PCCA gene. At 23 months of age she was diagnosed with genitourinary embryonal rhabdomyosarcoma. Conservative surgery, brachytherapy and nine cycles of chemotherapy with iphosphamide, vincristine and actinomycin were recommended by oncologists. Due to the possibility that the child could present decompensations, we elaborated three different courses of treatment: when the patient was stable (treatment 1), intermittent bolus feeding through gastrostomy, containing 70 kcal/kg/day and 1.4 g/kg/day of total protein (0.6 g/kg/day of natural protein and 0.8 g/kg/ day of amino acid-based formula) was prescribed; on the chemotherapy-days (treatment 2), diet consisted on continuous feeding, with the same energy and amino acid-based formula but half of natural protein intake; in case of decompensation (treatment 3), we increased by 10% the energy intake, and completely stopped natural protein in the diet but maintaining the amino acid-based formula. On chemotherapy-days carnitine was increased from 100 mg/kg/day to 150 mg/kg/ day, and N-carbamylglutamate was added.Through the 7 months with chemotherapy the patient did not suffer decompensations, while she maintained good nutritional status.Enteral continuous feeding by gastrostomy, amino acidbased formula, and preventive use of N-carbamylglutamate during chemotherapy-days are the principal measures we propose in these situations. Sentence Summary This article describes, for the first time, the management of a patient with propionic acidaemia through 7 months with chemotherapy. Enteral continuous feeding, amino acid-based formula, and preventive use of N-carbamylglutamate during the days of chemotherapy are the principal measures we propose in these situations. AbbreviationsE. Martín-Hernández : P. Quijada-Fraile : L. Oliveros-Leal :

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“…For instance, in propionic acidemia (PA), or a congenital deficiency of propionyl-CoA carboxylase, a decrease in NAG synthesis may occur either from competitive inhibition of NAGS by propionyl-CoA [29][30][31][32] or a relative depletion of hepatic acetyl-CoA or free coenzyme A [32]. Individual case reports suggest that NCG is helpful in the treatment of PA [33][34][35][36][37], but these are uncontrolled studies performed during an acute illness in which the effect of NCG is difficult to differentiate from that of standard care.…”

Section: Evaluating the Efficacy Of Therapeuticsmentioning

confidence: 99%

Stable isotopes in the diagnosis and treatment of inherited hyperammonemia

Tuchman

Mew

2016

J Pediatr Biochem

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Stable isotopes have greatly contributed to our understanding of nitrogen metabolism and the urea cycle. The measurement of urea flux via isotopic methods has traditionally been utilized to determine total body protein synthesis in subjects with an intact urea cycle. However, isotopic studies of nitrogen metabolism are also a useful adjunct to conventional clinical investigations in the diagnosis and management of the inherited hyperammonemias. Such studies offer a safe noninvasive method of measuring the reduction of in vivo hepatic ureagenesis, and thus may provide a more accurate measure of phenotypic severity in affected patients. In addition, isotopic methods are ideally suited to evaluate the efficacy of novel therapies to augment urea production.

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N‐Carbamylglutamate protects patients with decompensated propionicaciduria from hyperammonaemia

Cited by 66 publications

References 7 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

Nutritional and Pharmacological Management during Chemotherapy in a Patient with Propionic Acidaemia and Rhabdomyosarcoma Botryoides

Stable isotopes in the diagnosis and treatment of inherited hyperammonemia

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