Hypothesis: proposals for the management of a neonate at risk of hyperammonaemia due to a urea cycle disorder

Leonard, James V.; Platt, Martin Ward; Morris, Andrew A. M.

doi:10.1007/s00431-007-0486-z

Cited by 18 publications

(13 citation statements)

References 25 publications

(28 reference statements)

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“…These may also be indicated in milder UCDs or for NAGSD (which has substitutive therapy) for psychological reasons and to prepare for perinatal management [82-84]. Among the techniques that can be used (Table 3), mutation- or disease allele-tracking using chorionic villus samples, amniotic fluid cells or cultures thereof [85,86] is the method of choice since it gives rapid and clear-cut results relatively early on, with little fetal risk.…”

Section: Prenatal Testingmentioning

confidence: 99%

Suggested guidelines for the diagnosis and management of urea cycle disorders

Häberle

Boddaert

Burlina

et al. 2012

Orphanet J Rare Dis

511

623

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Urea cycle disorders (UCDs) are inborn errors of ammonia detoxification/arginine synthesis due to defects affecting the catalysts of the Krebs-Henseleit cycle (five core enzymes, one activating enzyme and one mitochondrial ornithine/citrulline antiporter) with an estimated incidence of 1:8.000. Patients present with hyperammonemia either shortly after birth (~50%) or, later at any age, leading to death or to severe neurological handicap in many survivors. Despite the existence of effective therapy with alternative pathway therapy and liver transplantation, outcomes remain poor. This may be related to underrecognition and delayed diagnosis due to the nonspecific clinical presentation and insufficient awareness of health care professionals because of disease rarity. These guidelines aim at providing a trans-European consensus to: guide practitioners, set standards of care and help awareness campaigns. To achieve these goals, the guidelines were developed using a Delphi methodology, by having professionals on UCDs across seven European countries to gather all the existing evidence, score it according to the SIGN evidence level system and draw a series of statements supported by an associated level of evidence. The guidelines were revised by external specialist consultants, unrelated authorities in the field of UCDs and practicing pediatricians in training. Although the evidence degree did hardly ever exceed level C (evidence from non-analytical studies like case reports and series), it was sufficient to guide practice on both acute and chronic presentations, address diagnosis, management, monitoring, outcomes, and psychosocial and ethical issues. Also, it identified knowledge voids that must be filled by future research. We believe these guidelines will help to: harmonise practice, set common standards and spread good practices with a positive impact on the outcomes of UCD patients.

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Section: Prenatal Testingmentioning

confidence: 99%

Suggested guidelines for the diagnosis and management of urea cycle disorders

Häberle

Boddaert

Burlina

et al. 2012

Orphanet J Rare Dis

511

623

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“…The administration of N-carbamylglutamate (carglumic acid, NCG) has been reported to be of benefit in several different conditions presenting with hyperammonemia 1. NCG is a synthetic analog of N-acetylglutamate (NAG) that activates carbamoyl-phosphate synthase I (CPS-I),2 the enzyme of the first and rate-limiting step of the urea cycle stimulating ureagenesis3 (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

New developments in the treatment of hyperammonemia: emerging use of carglumic acid

Daniotti¹,

Marca²,

Fiorini³

et al. 2011

IJGM

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Hyperammonemia is a true neonatal emergency with high toxicity for the central nervous system and developmental delay. The causes of neonatal hyperammonemia are genetic defects of urea cycle enzymes, organic acidemias, lysinuric protein intolerance, hyperammonemia–hyperornithinemia– homocitrullinemia syndrome, transient hyperammonemia of the newborn, and congenital hyperinsulinism with hyperammonemia. In some of these conditions the high blood ammonia levels are due to the reduction of N-acetylglutamate, an essential cofactor necessary for the function of the urea cycle, or to the reduction of carbamoyl-phosphate synthase-I activity. In these cases, N-carbamylglutamate (carglumic acid) can be administered together with the conventional therapy. Carglumic acid is an analog of N-acetylglutamate that has a direct action on carbamoyl-phosphate synthase-I. Its effects are reactivation of the urea cycle and reduction of plasma ammonia levels. As a consequence it improves the traditional treatment, avoiding the need of hemodialysis and peritoneal dialysis. In this review we evaluate the possible field of application of carglumic acid and its effectiveness and safety.

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“…However, this is practically difficult in the clinical setting as there can be a considerable delay after birth before spontaneous voiding of urine begins. It has recently been questioned whether benzoate conjugation is efficient in the first days of life as the enzymes responsible appear to need induction in newborn rodents 5. Substantial hippurate excretion was, however, found within 15 h of birth in patient 2.…”

Section: Discussionmentioning

confidence: 99%