Successful Early Management of a Female Patient With a Metabolic Stroke Due to Ornithine Transcarbamylase Deficiency

Tummolo, Albina; Favia, Vito; Bellantuono, R; Bellino, V.; Ranieri, A.; Morrone, Amelia; Palo, Tommaso De; Papadia, Francesco

doi:10.1097/pec.0b013e31828ec2b9

Cited by 9 publications

(4 citation statements)

References 14 publications

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“…Given its lack of significant toxicity, 24 NCG may be given orally in an emergency setting of undiagnosed first hyperammonemic episode, as in our patient. 2 Indeed, it has been used in single cases of ornithine transcarbamylase deficiency 25 and citrullinemia type 1. 26 Observations in CPS1D indicated that the deficiency must be partial to be NCG-sensitive, 11,12 and suggested that the specific mutations found in each patient can determine the degree of response to NCG.…”

Section: Discussionmentioning

confidence: 99%

N‐carbamoylglutamate‐responsive carbamoyl phosphate synthetase 1 (CPS1) deficiency: A patient with a novel CPS1 mutation and an experimental study on the mutation's effects

et al. 2019

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N ‐carbamoyl‐ l ‐glutamate (NCG), the N ‐acetyl‐ l ‐glutamate analogue used to treat N ‐acetylglutamate synthase deficiency, has been proposed as potential therapy of carbamoyl phosphate synthetase 1 deficiency (CPS1D). Previous findings in five CPS1D patients suggest that NCG‐responsiveness could be mutation‐specific. We report on a patient with CPS1D, homozygous for the novel p.(Pro1211Arg) CPS1 mutation, who presented at 9 days of life with hyperammonemic coma which was successfully treated with emergency measures. He remained metabolically stable on merely oral NCG, arginine, and modest protein restriction. Ammonia scavengers were only added after poor dietary compliance following solid food intake at age 1 year. The patient received a liver transplantation at 3.9 years of age, having normal cognitive, motor, and quality of life scores despite repeated but successfully treated episodes of hyperammonemia. Studies using recombinantly produced mutant CPS1 confirmed the partial nature of the CPS1D triggered by the p.(Pro1211Arg) mutation. This mutation decreased the solubility and yield of CPS1 as expected for increased tendency to misfold, and reduced the thermal stability, maximum specific activity ( V max ; ~2‐fold reduction), and apparent affinity (~5‐fold reduction) for ATP of the purified enzyme. By increasing the saturation of the NAG site in vivo, NCG could stabilize CPS1 and minimize the decrease in the effective affinity of the enzyme for ATP. These observations, together with prior experience, support the ascertainment of clinical responsiveness to NCG in CPS1 deficient patients, particularly when decreased stability or lowered affinity for NAG of the mutant enzyme are suspected or proven.

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Section: Discussionmentioning

confidence: 99%

N‐carbamoylglutamate‐responsive carbamoyl phosphate synthetase 1 (CPS1) deficiency: A patient with a novel CPS1 mutation and an experimental study on the mutation's effects

et al. 2019

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“…a, b) Axial FLAIR images (repetition time/echo time; 3000/100 ms) performed 3 months later indicated hyperintense areas in both insulae and frontal lobes treated with a combined therapy of continuous venovenous hemodialysis and N-carbamylglutamate. Her computed tomography examination performed a few weeks after the coma revealed a moderate hypoperfusion of the cerebral cortex without significant perfusive focal defects (7). Mutation analysis revealed a known nonsense spontaneous mutation c.67C>T (p.Arg23*) in exon 1 at heterozygous state at OTC gene in our patient (8).…”

Section: Successful Management Of Ornithine Transcarbamylase Deficienmentioning

confidence: 71%

Successful Management of Ornithine Transcarbamylase Deficiency Presenting with Reversible Metabolic Stroke in a Child

Dedeoğlu¹,

Kasapkara²,

Oğuz³

et al. 2018

jpr

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“…While a response to carbamylglutamate aids in the diagnosis, it is not in itself diagnostic of NAGS deficiency, as carbamylglutamate has been shown to be effective in some cases of other inherited metabolic disorders by augmenting ureagenesis and decreasing plasma ammonia, including CPS1 deficiency, ornithine transcarbamylase (OTC) deficiency, citrullinemia type I (argininosuccinic acid synthetase deficiency), methylmalonic acidemia (MMA), propionic acidemia (PA), isovaleric acidemia (IVA), carbonic anhydrase VA (CAVA) deficiency, and multiple acyl-CoA dehydrogenase deficiency (MADD). Carbamylglutamate has been used in acute treatment of hyperammonemia in some cases of CPS1 deficiency [47][48][49], OTC deficiency [50], PA [51][52][53][54][55], MMA [51][52][53][54][55][56], IVA [57], CAVA deficiency [58,59], and MADD [60] as well as long-term management of some cases of CPS1 deficiency [48,61], citrullinemia type I [62], OTC deficiency [50], PA [63,64], MMA [64], and MADD [60].…”

Section: Discussionmentioning

confidence: 99%

Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature

Kenneson

Singh

2020

Orphanet J Rare Dis

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Background N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia which can cause significant morbidity and mortality. Since its recognition in 1981, NAGS deficiency has been treated with carbamylglutamate with or without other measures (nutritional, ammonia scavengers, dialytic, etc.). We conducted a systematic literature review of NAGS deficiency to summarize current knowledge around presentation and management. Methods Case reports and case series were identified using the Medline database, as well as references from other articles and a general internet search. Clinical data related to presentation and management were abstracted by two reviewers. Results In total, 98 cases of NAGS deficiency from 79 families, in 48 articles or abstracts were identified. Of these, 1 was diagnosed prenatally, 57 were neonatal cases, 34 were post-neonatal, and 6 did not specify age at presentation or were asymptomatic at diagnosis. Twenty-one cases had relevant family history. We summarize triggers of hyperammonemic episodes, diagnosis, clinical signs and symptoms, and management strategies. DNA testing is the preferred method of diagnosis, although therapeutic trials to assess response of ammonia levels to carbamylglutamate may also be helpful. Management usually consists of treatment with carbamylglutamate, although the reported maintenance dose varied across case reports. Protein restriction was sometimes used in conjunction with carbamylglutamate. Supplementation with citrulline, arginine, and sodium benzoate also were reported. Conclusions Presentation of NAGS deficiency varies by age and symptoms. In addition, both diagnosis and management have evolved over time and vary across clinics. Prompt recognition and appropriate treatment of NAGS deficiency with carbamylglutamate may improve outcomes of affected individuals. Further research is needed to assess the roles of protein restriction and supplements in the treatment of NAGS deficiency, especially during times of illness or lack of access to carbamylglutamate.

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Successful Early Management of a Female Patient With a Metabolic Stroke Due to Ornithine Transcarbamylase Deficiency

Abstract: This case demonstrates that clinical benefits can be obtained by beginning aggressive treatment of OTC-D within a few hours of the onset of severe neurological symptoms even in the absence of altered biochemical markers.

Cited by 9 publications

References 14 publications

N‐carbamoylglutamate‐responsive carbamoyl phosphate synthetase 1 (CPS1) deficiency: A patient with a novel CPS1 mutation and an experimental study on the mutation's effects

N‐carbamoylglutamate‐responsive carbamoyl phosphate synthetase 1 (CPS1) deficiency: A patient with a novel CPS1 mutation and an experimental study on the mutation's effects

Successful Management of Ornithine Transcarbamylase Deficiency Presenting with Reversible Metabolic Stroke in a Child

Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature

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