Diagnostic and Management Issues in Patients with Late-Onset Ornithine Transcarbamylase Deficiency

Ibrahim, Majitha Seyed; Gold, Jessica I.; Woodall, Alison; Yılmaz, Bilge; Gissen, Paul; Stępień, Karolina M.

doi:10.3390/children10081368

Cited by 6 publications

(2 citation statements)

References 83 publications

(179 reference statements)

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“…If severe, this can result in life-threatening hyperammonemia in the neonatal window. If mild, hyperammonemia may only occur with significant metabolic stress [2 ▪ ,4,5].…”

Section: Introductionmentioning

confidence: 99%

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Urea cycle disorders in critically Ill adults

Long,

Kruser,

Quinonez

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review Urea cycle disorders (UCDs) cause elevations in ammonia which, when severe, cause irreversible neurologic injury. Most patients with UCDs are diagnosed as neonates, though mild UCDs can present later - even into adulthood - during windows of high physiologic stress, like critical illness. It is crucial for clinicians to understand when to screen for UCDs and appreciate how to manage these disorders in order to prevent devastating neurologic injury or death. Recent findings Hyperammonemia, particularly if severe, causes time- and concentration-dependent neurologic injury. Mild UCDs presenting in adulthood are increasingly recognized, so broader screening in adults is recommended. For patients with UCDs, a comprehensive, multitiered approach to management is needed to prevent progression and irreversible injury. Earlier exogenous clearance is increasingly recognized as an important complement to other therapies. Summary UCDs alter the core pathway for ammonia metabolism. Screening for mild UCDs in adults with unexplained neurologic symptoms can direct care and prevent deterioration. Management of UCDs emphasizes decreasing ongoing ammonia production, avoiding catabolism, and supporting endogenous and exogenous ammonia clearance. Core neuroprotective and supportive critical care supplements this focused therapy.

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“…If severe, this can result in life-threatening hyperammonemia in the neonatal window. If mild, hyperammonemia may only occur with significant metabolic stress [2 ▪ ,4,5].…”

Section: Introductionmentioning

confidence: 99%

“…While most primary UCDs are diagnosed in the neonatal window, mild UCDs, sometimes termed “partial,” or “late-onset” do occur. Patients with mild UCDs can present at any age, even well into later adulthood [2 ▪ ,4,5].…”

Section: Introductionmentioning

confidence: 99%

Urea cycle disorders in critically Ill adults

Long,

Kruser,

Quinonez

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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The management and clinical outcomes of pregnancies in women with urea cycle disorders: A review of the literature and results of an international survey

Stepien,

Langendonk,

Dao

et al. 2023

J of Inher Metab Disea

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An increasing number of women with urea cycle disorders (UCDs) are reaching child‐bearing age and becoming pregnant. Improved diagnostics and increased awareness of inherited metabolic diseases has also led to more previously undetected women being diagnosed with a UCD during or shortly after pregnancy. Pregnancy increases the risk of acute metabolic decompensation with hyperammonemia—which can occur in any trimester, and/or the postpartum period, and may lead to encephalopathy, psychosis, coma, and even death, if not diagnosed promptly and treated appropriately. There are also (theoretical) concerns that a maternal UCD, or its treatment, may cause potential risks for the unborn child. Currently evidence on management and outcome of pregnancies in UCDs is limited to case reports and there are no clear guidelines. In order to inform management and investigate outcomes of pregnancies in women with a UCD, we performed a retrospective review of published cases and analyzed data collected from an international online survey. We conclude that, although risk during the intra‐ and postpartum period exists, multidisciplinary management by an experienced team and a prospective plan usually result in successful pregnancy, labor, delivery, and postpartum period. No deaths were reported in mothers managed accordingly. With the exception of male neonates with Ornithine Transcarbamylase deficiency, the clinical outcome of children born to mothers with UCDs appears positive, although follow‐up is limited. The outcome for women presenting with a first acute metabolic decompensation during pregnancy or postpartum is less favorable. Deaths were associated with diagnostic delay/late management of hyperammonemia in previously undiagnosed women.

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Genetic aetiologies of acute liver failure

Hegarty,

Thompson

2024

J of Inher Metab Disea

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Acute liver failure (ALF) is a rare, rapidly evolving, clinical syndrome with devastating consequences where definitive treatment is by emergency liver transplantation. Establishing a diagnosis can be challenging and, historically, the cause of ALF was unidentified in up to half of children. However, recent technological and clinical advances in genomic medicine have led to an increasing proportion being diagnosed with monogenic aetiologies of ALF. The conditions encountered include a diverse group of inherited metabolic disorders each with prognostic and treatment implications. Often these disorders are clinically indistinguishable and may even mimic disorders of immune regulation or red cell disorders. Rapid genomic sequencing for children with ALF is, therefore, a key component in the diagnostic work up today. This review focuses on the monogenic aetiologies of ALF.

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Diagnostic and Management Issues in Patients with Late-Onset Ornithine Transcarbamylase Deficiency

Cited by 6 publications

References 83 publications

Urea cycle disorders in critically Ill adults

Urea cycle disorders in critically Ill adults

The management and clinical outcomes of pregnancies in women with urea cycle disorders: A review of the literature and results of an international survey

Genetic aetiologies of acute liver failure

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