New insights into the genetics of 5-oxoprolinase deficiency and further evidence that it is a benign biochemical condition

Calpena, Eduardo; Deshpande, Anup; Yap, Sufin; Kumar, Akhilesh; Manning, N. J.; Bachhawat, Anand K.; Espinós, Carmen

doi:10.1007/s00431-014-2397-0

Cited by 10 publications

(11 citation statements)

References 14 publications

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“…Relatively few cases have been reported to date. Inherited 5-oxoprolinase deficiency had previously been considered to be a benign biochemical condition rather than a severe disease [4]. 5-Oxoprolinuria may present as an epiphenomenon in other diseases, which could leave the diagnosis in confusion.…”

Section: Discussionmentioning

confidence: 99%

“…OPLAH gene is located on chromosome 8q24.3, including at least 26 exons [16]. Five mutations have been reported till now [2][3][4]. In 2012, c.2601_2602insC (p.H870Pfs * 92) mutation was identified from a 10-year-old boy.…”

Section: Discussionmentioning

confidence: 99%

“…5-Oxoprolinase deficiency is a very rare autosomal recessive disorder caused by mutations in the OPLAH gene (OMIM 614243). Only very few cases of 5-oxoprolinase deficiency have been documented worldwide [2][3][4]. The patients present with a number of clinical symptoms including mental retardation, enterocolitis, hypoglycemia, microcytic anemia, microcephaly and renal stones [5].…”

Section: Introductionmentioning

confidence: 99%

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Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5-oxoprolinase deficiencies

Yuan

Liu

et al. 2015

Brain and Development

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5-oxoprolinase deficiencies

Yuan

Liu

et al. 2015

Brain and Development

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“…Glutathione synthase deficiency is a rare autosomal recessive condition characterised by ataxia, haemolytic anaemia, chronic MA and progressive neurological symptoms [4,6]. Whilst neurological sequelae have been reported in some patients [4] with 5-oxoprolinase deficiency, this defect tends to be less severe and can exist as a benign condition [3]. These conditions usually have an insidious onset during childhood.…”

Section: Discussionmentioning

confidence: 99%

“…This reveals whether the acidosis is due to changes in bicarbonate or chloride or whether other anions are responsible for the disturbance. The anion gap is calculated as follows: [Na + +K + ]−[HCO 3 − +Cl − ]. A normal anion gap is 10-18 mmol/l.…”

Section: Introductionmentioning

confidence: 99%

Transient 5-oxoprolinuria: unusually high anion gap acidosis in an infant

et al. 2015

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Transient 5-oxoprolinuria is a phenomenon that is well recognised in adults. We illustrate an unusual paediatric case of transient 5-oxoprolinuria presenting during an episode of severe sepsis with concomitant paracetamol use. The 15-month-old patient had an extremely high anion gap metabolic acidosis. Adequate resuscitation failed to correct the biochemical disturbance, and high levels of 5-oxoproline were identified. A combination of haemofiltration, replenishment of glutathione stores with N-acetylcysteine and cessation of paracetamol administration resulted in the resolution of the acidosis. Subsequent testing following treatment of the sepsis revealed no ongoing 5-oxoprolinuria.Conclusion: Transient 5-oxoprolinuria has been previously reported in the adult population during episodes of severe sepsis and various pharmaceutical interventions. This case illustrates that it is a phenomenon that should be considered in paediatric patients where a very high anion gap metabolic acidosis exists that cannot be explained by the biochemical indices.

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Inborn errors of enzymes in glutamate metabolism

Rumping

Vringer

Houwen

et al. 2019

J of Inher Metab Disea

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Glutamate is involved in a variety of metabolic pathways. We reviewed the literature on genetic defects of enzymes that directly metabolise glutamate, leading to inborn errors of glutamate metabolism. Seventeen genetic defects of glutamate metabolising enzymes have been reported, of which three were only recently identified. These 17 defects affect the inter‐conversion of glutamine and glutamate, amino acid metabolism, ammonia detoxification, and glutathione metabolism. We provide an overview of the clinical and biochemical phenotypes of these rare defects in an effort to ease their recognition. By categorising these by biochemical pathway, we aim to create insight into the contributing role of deviant glutamate and glutamine levels to the pathophysiology. For those disorders involving the inter‐conversion of glutamine and glutamate, these deviant levels are postulated to play a pivotal pathophysiologic role. For the other IEM however—with the exception of urea cycle defects—abnormal glutamate and glutamine concentrations were rarely reported. To create insight into the clinical consequences of disturbed glutamate metabolism—rather than individual glutamate and glutamine levels—the prevalence of phenotypic abnormalities within the 17 IEM was compared to their prevalence within all Mendelian disorders and subsequently all disorders with metabolic abnormalities notated in the Human Phenotype Ontology (HPO) database. For this, a hierarchical database of all phenotypic abnormalities of the 17 defects in glutamate metabolism based on HPO was created. A neurologic phenotypic spectrum of developmental delay, ataxia, seizures, and hypotonia are common in the inborn errors of enzymes in glutamate metabolism. Additionally, ophthalmologic and skin abnormalities are often present, suggesting that disturbed glutamate homeostasis affects tissues of ectodermal origin: brain, eye, and skin. Reporting glutamate and glutamine concentrations in patients with inborn errors of glutamate metabolism would provide additional insight into the pathophysiology.

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New insights into the genetics of 5-oxoprolinase deficiency and further evidence that it is a benign biochemical condition

Abstract: Taken together, this report further suggests that hereditary 5-oxoprolinase deficiency is a benign biochemical condition caused by mutations in the OPLAH gene, which are transmitted in an autosomal recessive manner, but 5-oxoprolinuria may be a chance association in other disorders.

Cited by 10 publications

References 14 publications

Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5-oxoprolinase deficiencies

Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5-oxoprolinase deficiencies

Transient 5-oxoprolinuria: unusually high anion gap acidosis in an infant

Inborn errors of enzymes in glutamate metabolism

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