3-Methylglutaconic aciduria, a frequent but underrecognized finding in carbamoyl phosphate synthetase I deficiency

Rokicki, Dariusz; Pajdowska, Magdalena; Trubicka, Joanna; Thong, Meow‐Keong; Ciara, Elżbieta; Piekutowska‐Abramczuk, Dorota; Pronicki, Maciej; Sikora, R.; Haidar, Rijad; Ołtarzewski, Mariusz; Jabłońska, Ewa; Muthukumarasamy, Premala; Sthaneswar, Pavai; Gan, Chin Seng; Krajewska‐Walasek, M; Carrozzo, Rosalba; Verrigni, Daniela; Semeraro, Michela; Rizzo, Cristiano; Taurisano, Roberta; Alhaddad, Bader; Kovács-Nagy, Réka; Haack, Tobias B.; Dionisi‐Vici, Carlo; Pronicka, Ewa; Wortmann, Saskia B.

doi:10.1016/j.cca.2017.05.023

Cited by 13 publications

(15 citation statements)

References 18 publications

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“…Carbamoyl phosphate synthetase 1 deficiency (CPS1D; MIM237300) is an autosomal recessive genetic disorder, characterized by devastating metabolic disease dominated by severe hyperammonemia, and some patients also suffer from brain white matter changes . The time of onset presents as either in neonates or in a more insidious late‐onset.…”

Section: Introductionmentioning

confidence: 80%

“…is an autosomal recessive genetic disorder, characterized by devastating metabolic disease dominated by severe hyperammonemia, and some patients also suffer from brain white matter changes. 1,2 The time of onset presents as either in neonates or in a more insidious late-onset. The morbidity of CPS1D is estimated 1:50 000-1:300 000 in worldwide, of which 1:800 000 in Japan and 1:50 000-1:100 000 in European population.…”

Section: Introductionmentioning

confidence: 99%

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Two novel CPS1 mutations in a case of carbamoyl phosphate synthetase 1 deficiency causing hyperammonemia and leukodystrophy

Chen

Yuan

Sun

et al. 2018

Clinical Laboratory Analysis

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This study described the specific clinical characteristics and the variations of physiological and biochemical indices in a Chinese neonatal patient with CPS1D, which facilitated the diagnosis and mechanism research of the disease. Two novel causative missense mutations were identified, which enriched the mutation spectrum of CPS1D in China and worldwide. Advice of prenatal diagnosis was given to the family for a new pregnancy.

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Section: Introductionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Two novel CPS1 mutations in a case of carbamoyl phosphate synthetase 1 deficiency causing hyperammonemia and leukodystrophy

Chen

Yuan

Sun

et al. 2018

Clinical Laboratory Analysis

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“…Carbamoyl phosphate synthetase I (CPS1) deficiency (CPS1D) is a rare autosomal recessive urea cycle disorder, characterized by hyperammonemia with the incidence of 1/50,000 to 1/300,000 (Díez-Fernández et al, 2015). CPS1D is currently divided into two types of neonatal onset and late onset, whereas CPS1D with severe manifestations of hyperammonemia is common in neonatal-onset patients (Choi et al, 2017; Rokicki et al, 2017; Yang et al, 2017; Zhang et al, 2018). Typically, the neonatal-onset patient with CPS1D appears to be healthy at birth, but deteriorates rapidly into severe hyperammonemia, presenting poor feeding, vomiting, hypotonia, irritability, seizures, hypothermia, lethargy, coma, apnea, and even death after first feeding (Funghini et al, 2012; Choi et al, 2017; Rokicki et al, 2017; Zhang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…It is difficult to timely diagnose CPS1D due to atypical manifestations like sudden onset, rapid progress, and low morbidity, as well as complicated and non-recurrent genetic mutations in CPS1 gene (Choi et al, 2017; Rokicki et al, 2017; Zhang and Li, 2017). For more than a decade, the diagnosis of CPS1D has been mainly relied on the laboratory tests of tandem mass spectrometry (MS/MS) including liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC/MS).…”

Section: Introductionmentioning

confidence: 99%

“…However, this technology cannot differentiate CPS1D from N -acetylglutamate synthase deficiency (NAGSD) in UCDs due to their similar intermediate metabolites. Until recently, next-generation sequencing (NGS), a powerful DNA sequencing technology, has revolutionized genomic research with great utility in the molecular diagnosis of genetic disorders (Choi et al, 2017; Jia et al, 2017; Rokicki et al, 2017; Li et al, 2018; Zhang et al, 2018), and has been proven reliable and important to detect CPS1 mutation for early diagnosis of CPS1D, as the severity of clinical manifestations in CPS1D patients is determined by the extent of CPS1 deficiency (Choi et al, 2017; Chen et al, 2018; Zhang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Novel Neonatal Variants of the Carbamoyl Phosphate Synthetase 1 Deficiency: Two Case Reports and Review of Literature

et al. 2019

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Carbamoyl phosphate synthetase I (CPS1) deficiency (CPS1D), is a rare autosomal recessive disorder, characterized by life-threatening hyperammonemia. In this study, we presented the detailed clinical features and genetic analysis of two patients with neonatal-onset CPS1D carrying two compound heterozygous variants of c.1631C > T (p.T544M)/c.1981G > T (p.G661C), and c.2896G > T (p.E966X)/c622-3C > G in CPS1 gene, individually. Out of them, three variants are novel, unreported including a missense (c.1981G > T, p.G661C), a nonsense (c.2896G > T, p.E966X), and a splicing change of c.622-3C > G. We reviewed all available publications regarding CPS1 mutations, and in total 264 different variants have been reported, with majority of 157 (59.5%) missense, followed by 35 (13.2%) small deletions. This study expanded the mutational spectrum of CPS1 . Moreover, our cases and review further support the idea that most (≥90%) of the mutations were “private” and only ∼10% recurred in unrelated families.

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Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision

Häberle

Burlina²,

Chakrapani

et al. 2019

J of Inher Metab Disea

318

478

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In 2012, we published guidelines summarizing and evaluating late 2011 evidence for diagnosis and therapy of urea cycle disorders (UCDs). With 1:35 000 estimated incidence, UCDs cause hyperammonemia of neonatal (~50%) or late onset that can lead to intellectual disability or death, even while effective therapies do exist. In the 7 years increased awareness among health professionals and patient families. However, underrecognition and delayed diagnosis of UCDs still appear widespread. It was therefore necessary to revise the original guidelines to ensure an up-to-date frame of reference for professionals and patients as well as for awareness campaigns. This was accomplished by keeping the original spirit of providing a trans-European consensus based on robust evidence (scored with GRADE methodology), involving professionals on UCDs from nine countries in preparing this consensus. We believe this revised guideline, which has been reviewed by several societies that are involved in the management of UCDs, will have a positive impact on the outcomes of patients by establishing common standards, and spreading and harmonizing good practices. It may also promote the identification of knowledge voids to be filled by future research.

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3-Methylglutaconic aciduria, a frequent but underrecognized finding in carbamoyl phosphate synthetase I deficiency

Cited by 13 publications

References 18 publications

Two novel CPS1 mutations in a case of carbamoyl phosphate synthetase 1 deficiency causing hyperammonemia and leukodystrophy

Two novel CPS1 mutations in a case of carbamoyl phosphate synthetase 1 deficiency causing hyperammonemia and leukodystrophy

Novel Neonatal Variants of the Carbamoyl Phosphate Synthetase 1 Deficiency: Two Case Reports and Review of Literature

Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision

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