Prenatal diagnosis of the urea cycle diseases: A survey of the european cases

Kamoun, P.; Fensom, A. H.; Shin, Yoon S.; Bakker, Egbert; Colombo, Jean‐Pierre; Münnich, Arnold; Bird, Sara; Canini, Silvana; Huijmans, J. G. M.; Chadefaux-Vekemans, Bernadette; Whitfield, A. E.; Kleijer, W. J.

doi:10.1002/ajmg.1320550220

Cited by 20 publications

(13 citation statements)

References 18 publications

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“…However, such an intervention is associated with a higher risk of complications, as compared with CVS or amniocentesis. In contrast to DNA-based prenatal diagnosis, enzymatic diagnosis of CPS1 deficiency by fetal liver biopsy may yield an ambiguous (Yoshino et al, 1997), or even misleading, result, as reported in one from eight diagnoses in a recent survey of European cases (Kamoun et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1

et al. 1998

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Carbamoyl phosphate synthetase I (CPS1) deficiency is an autosomal recessive metabolic disorder affecting the first enzymatic step of urea cycle. We report a consanguineous family in which the index patient died at 11 days of age from a severe form of CPS1 deficiency. Initial diagnosis was based on clinical histopathological, and enzymatic investigations. Direct sequencing of the complete CPS1 coding region revealed a disease-associated homozygous Thr544Met mutation in CPS1. On the basis of the molecular data, prenatal diagnosis was established for genomic DNA and performed at gestational week 12, after chorionic villus sampling. The fetus was homozygous for the Thr544Met mutation, and termination of pregnancy was elected. Histopathological signs of the hepatocellular metabolic disorder similar to that of the index patient were found in fetal liver thus giving morphological evidence for this hereditary error of urea cycle function as early as gestational week 12.

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Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1

et al. 1998

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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. Amniotic fluid citrulline and ASA determinations are also suitable for respective ASSD and ASLD prenatal diagnosis [86-88].…”

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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“…Elevated levels of argininosuccinic acid in the amniotic fluid can also reliably detect affected fetuses 40, 41, 42 . Analysis of enzyme activity by either direct methods from chorionic villus tissue or amniocytes or indirect methods such as 14 C-citrulline incorporation in uncultured chorionic villus samples, have been successfully performed 24, 43 .…”

Section: Diagnosismentioning

confidence: 99%

Argininosuccinate lyase deficiency

Nagamani

Erez

Lee

2012

Genetics in Medicine

100

105

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SUMMARY The urea cycle consists of six consecutive enzymatic reactions that convert waste nitrogen into urea. Deficiencies of any of these enzymes of the cycle result in urea cycle disorders (UCD), a group of inborn errors of hepatic metabolism that often result in life threatening hyperammonemia. Argininosuccinate Lyase (ASL) catalyzes the fourth reaction in this cycle resulting in the breakdown of argininosuccinic acid to arginine and fumarate. Argininosuccinate Lyase deficiency (ASLD) is the second most common UCD with a prevalence of ~1 in 70,000 live births. ASLD can manifest as either a severe neonatal onset form with hyperammonemia within the first few days after birth or as a late onset form with episodic hyperammonemia and/or long term complications that include liver dysfunction, neuro-cognitive deficits and hypertension. These long term complications can occur in the absence of hyperammonemic episodes implying that ASL has functions outside of its role in ureagenesis and the tissue specific lack of ASL may be responsible for these manifestations. The biochemical diagnosis of ASLD is typically established with elevation of plasma citrulline together with elevated argininosuccinic acid in the plasma or urine. Molecular genetic testing of ASL and assay of ASL enzyme activity are helpful when the biochemical findings are equivocal. However, there is no correlation between the genotype, or enzyme activity and clinical outcome. Treatment of acute metabolic decompensations with hyperammonemia involves discontinuing oral protein intake; supplementing oral intake with intravenous lipids and/or glucose, and use of intravenous arginine and nitrogen scavenging therapy. Dietary restriction of protein and dietary supplementation with arginine are the mainstays in long-term management. Orthotopic liver transplantation is best considered only in patients with recurrent hyperammonemia or metabolic decompensations resistant to conventional medical therapy.

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Prenatal diagnosis of the urea cycle diseases: A survey of the european cases

Cited by 20 publications

References 18 publications

Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1

Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1

Suggested guidelines for the diagnosis and management of urea cycle disorders

Argininosuccinate lyase deficiency

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