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

Yap, Sufin; Leong, Huey Yin; Aziz, Fadzlina Abdul; Hassim, Haszlin; Sthaneshwar, Pavai; Teh, Ser Huy; Abdullah, Ili Syazwana; Ngu, Lock Hock; Zeriouh, Mohamed

doi:10.1159/000443630

Cited by 14 publications

(11 citation statements)

References 19 publications

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“…There are reports on the rapid amelioration of patients’ clinical condition with precocious administration of NCG, regardless of the extent of hyperammonemia [ 7 – 11 ], suggesting that continuous NCG treatment may be effective. We report our highly positive clinical experience with continuous administration of NCG for 6 years in a patient with PA who presented frequently with hyperammonemia believed to reflect secondary blockage of NAG synthase by PA metabolites [ 2 , 3 ].…”

Section: Discussionmentioning

confidence: 99%

Long-term continuous N-carbamylglutamate treatment in frequently decompensated propionic acidemia: a case report

et al. 2018

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BackgroundPropionic acidemia is a rare autosomal recessive inherited metabolic disorder that can inhibit the synthesis of N-acetylglutamate, the obligatory activator in urea synthesis, leading to hyperammonemia. N-carbamylglutamate ameliorates hyperammonemia in decompensated propionic acidemia. The effects of long-term continuous N-acetylglutamate administration in such patients are unknown. We report our clinical experience with continuous administration of N-acetylglutamate for 6 years in a patient with propionic acidemia frequently presenting with hyperammonemia.Case presentationA male Caucasian patient with frequently decompensated propionic acidemia and hyperammonemia was admitted 78 times for acute attacks during the first 9 years of his life. Continuous daily treatment with oral N-carbamylglutamate 100 mg/kg (50 mg/kg after 6 months) was initiated. During 6 years of treatment, he had a significant decrease in his mean plasma ammonia levels (75.7 μmol/L vs. 140.3 μmol/L before N-carbamylglutamate therapy, p < 0.005 [normal range 50–80 μmol/L]) and fewer acute episodes (two in 6 years).ConclusionOur results suggest a benefit of N-acetylglutamate administration outside the emergency setting. If this observation is confirmed, future studies should aim to optimize the dosage and explore effects of the dosage requirements on other drugs and on protein tolerance.

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Section: Discussionmentioning

confidence: 99%

Long-term continuous N-carbamylglutamate treatment in frequently decompensated propionic acidemia: a case report

et al. 2018

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“…Indeed, the use of nutritional approaches to optimize meat fatty acid composition has been a popular research topic, for example, supplying specific additives in diets such as linseeds, plant extracts [4,5]. The application of N-carbamylglutamate (NCG) as a dietary supplement for the health of humans and animals also has gained increasing interest [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Meat Quality and Fatty Acid Profiles of Chinese Ningxiang Pigs Following Supplementation with N-Carbamylglutamate

Xing

Xie

et al. 2020

Animals

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The present study evaluated the effects of dietary N-carbamylglutamate (NCG) on carcass traits, meat quality, and fatty acid profiles in the longissimus dorsi muscle and adipose tissues of Chinese Ningxiang pigs. A total of 36 castrated female pigs with a similar initial weight (43.21 ± 0.57 kg) were randomly assigned to two treatments (with six pens per treatment and three pigs per pen) and fed either a basal diet or a basal diet supplemented with 0.08% NCG for 56 days. Results showed that dietary NCG reduced shear force (p = 0.004) and increased drip loss (p = 0.044) in longissimus dorsi muscle of Ningxiang pigs. Moreover, increased levels of oleic acid (C18:1n9c) (p = 0.009), paullinic acid (C20:1) (p = 0.004), and α-linolenic acid (C18:3n3) (p < 0.001), while significant reduction in the proportions of arachidonic acid (C20:4n6) (p < 0.001) and polyunsaturated fatty acid (PUFA) (p = 0.017) were observed in the longissimus dorsi muscle of pigs fed NCG when compared with those fed the control diet. As for adipose tissues, the C20:1 (p = 0.045) proportion in dorsal subcutaneous adipose (DSA), as well as the stearic acid (C18:0) (p = 0.018) level in perirenal adipose (PA) were decreased when pigs were fed the NCG diet compared with those of the control diet. In contrast, the margaric acid (C17:0) (p = 0.043) proportion in PA were increased. Moreover, the NCG diet produced PA with a greater proportion of total PUFAs (p = 0.001) (particularly linoleic acid (C18:2n6c) (p = 0.001)) compared with those produced by the control diet. These findings suggest that dietary NCG has beneficial effects by decreasing the shear force and improving the healthfulness of fatty acid profiles, providing a novel strategy for enhancing meat quality of pigs.

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“…The effect of NCG in these cases was quite remarkable and significant reduction of ammonia levels was achieved within 12 h in most cases with a dose of 100–250 mg/kg/day. The observed responses obviated the use of scavenger medications or hemodialysis after the stabilization of ammonia levels [43,47,49,53]. Recent biochemical studies using heavy-isotope labeled urea precursors revealed that the administration of NCG accelerated the production of urea, validating the effectiveness of NGC in PA [8,9,54].…”

Section: Further Characterization Of Efficacy Of Ncg In Various Comentioning

confidence: 99%

Efficacy of N-carbamoyl-L-glutamic acid for the treatment of inherited metabolic disorders

Chapel-Crespo

Diaz

Oishi

2016

Expert Review of Endocrinology & Metabolism

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Introduction N-carbamoyl-L-glutamic acid (NCG) is a synthetic analogue of N-acetyl glutamate (NAG) that works effectively as a cofactor for carbamoyl phosphate synthase 1 and enhances ureagenesis by activating the urea cycle. NCG (brand name, Carbaglu) was recently approved by the United States Food and Drug Administration (US FDA) for the management of NAGS deficiency and by the European Medicines Agency (EMA) for the treatment of NAGS deficiency as well as for the treatment of hyperammonenia in propionic, methylmalonic and isovaleric acidemias in Europe. Areas covered The history, mechanism of action, and efficacy of this new drug are described. Moreover, clinical utility of NCG in a variety of inborn errors of metabolism with secondary NAGS deficiency is discussed. Expert commentary NCG has favorable pharmacological features including better bioavailability compared to NAG. The clinical use of NCG has proven to be so effective as to make dietary protein restriction unnecessary for patients with NAGS deficiency. It has been also demonstrated to be effective for hyperammonemia secondary to other types of inborn errors of metabolism. NCG may have additional therapeutic potential in conditions such as hepatic hyperammonemic encephalopathy secondary to chemotherapies or other liver pathology.

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

Cited by 14 publications

References 19 publications

Long-term continuous N-carbamylglutamate treatment in frequently decompensated propionic acidemia: a case report

Long-term continuous N-carbamylglutamate treatment in frequently decompensated propionic acidemia: a case report

Meat Quality and Fatty Acid Profiles of Chinese Ningxiang Pigs Following Supplementation with N-Carbamylglutamate

Efficacy of N-carbamoyl-L-glutamic acid for the treatment of inherited metabolic disorders

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