Significant Hepatic Involvement in Patients with Ornithine Transcarbamylase Deficiency

Gallagher, Renata C.; Lam, Christina; Wong, Derek A.; Cederbaum, Stephen D.; Sokol, Ronald J.

doi:10.1016/j.jpeds.2013.12.024

Cited by 57 publications

(50 citation statements)

References 58 publications

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“…We reviewed the medical records of patients (n=71) enrolled in the longitudinal study at two centers to assess what proportion with OTCD had evidence of “liver failure” (defined as INR ≥ 2.0), liver dysfunction (INR 1.5–1.99), or hepatocellular injury (AST/ALT≥ 250 IU/L) [21]. 57% of the 49 patients with symptomatic OTCD had abnormal liver function tests: 29% met the criteria above for liver failure, 20% had liver dysfunction, and 8% had isolated hepatocellular injury.…”

Section: Resultsmentioning

confidence: 99%

A longitudinal study of urea cycle disorders

Batshaw

Tuchman

Summar

et al. 2014

Molecular Genetics and Metabolism

165

135

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The urea cycle disorders consortium (UCDC) is a member of the NIH funded Rare Diseases Clinical Research Network and is performing a longitudinal study of 8 urea cycle disorders (UCD) with initial enrollment beginning in 2006. The consortium consists of 14 sites in the U.S., Canada and Europe. This report summarizes data mining studies of 614 patients with UCD enrolled in the UCDC’s longitudinal study protocol. The most common disorder is ornithine transcarbamylase deficiency, accounting for more than half of the participants. We calculated the overall prevalence of urea cycle disorders to be 1/35,000, with 2/3rds presenting initial symptoms after the newborn period. We found the mortality rate to be 24% in neonatal onset cases and 11% in late onset cases. The most common precipitant of clinical hyperammonemic episodes in the post-neonatal period was intercurrent infections. Elevations in both blood ammonia and glutamine appeared to be biomarkers for neurocognitive outcome. In terms of chronic treatment, low protein diet appeared to result in normal weight but decreased linear growth while N-scavenger therapy with phenybutyrate resulted in low levels of branched chain amino acids. Finally, we found an unexpectedly high risk for hepatic dysfunction in patients with ornithine transcarbamylase deficiency. This natural history study illustrates how a collaborative study of a rare genetic disorder can result in an improved understanding of morbidity and disease outcome.

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Section: Resultsmentioning

confidence: 99%

A longitudinal study of urea cycle disorders

Batshaw

Tuchman

Summar

et al. 2014

Molecular Genetics and Metabolism

165

135

View full text Add to dashboard Cite

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“…Besides the neurologic involvement, extraneurological symptoms are also present and the liver is the main affected organ. Hepatic involvement in argininemia can vary from mild hepatocellular injury with transient elevations of liver transaminases to coagulation abnormalities and hepatic failure as in other UCD [7-9, 12]. …”

Section: Discussionmentioning

confidence: 99%

Coagulation Disturbances in Patients with Argininemia

et al. 2018

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Background: Argininemia is an autosomal recessive urea cycle disorder (UCD). Unlike other UCD, hyperammonemia is rarely seen. Patients usually present in childhood with neurological symptoms. Uncommon presentations like neonatal cholestasis or cirrhosis have been reported. Although transient elevations of liver transaminases and coagulopathy have been reported during hyperammonemia episodes, a permanent coagulopathy has never been reported. Methods: In this retrospective study, coagulation disturbances are examined in 6 argininemia patients. All of the patients were routinely followed up for hepatic involvement due to argininemia. Laboratory results, including liver transaminases, albumin, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and clotting factor levels, were assessed in all of the patients. Results: All of the patients had a prolonged PT and an increased INR, while none of the patients had a prolonged aPTT. Five patients had slightly elevated liver transaminases. A liver biopsy was performed in 1 patient but neither cirrhosis nor cholestasis was documented. Five of the 6 patients had low factor VII and factor IX levels, while other clotting factors were normal. Conclusions: Argininemia patients should be investigated for coagulation disorders even if there is no apparent liver dysfunction or major bleeding symptoms.

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“…Some patients with OTCD experience liver damage evidenced by elevated plasma alanine aminotransferase (ALT) and prolonged coagulation time resulting in increased international normalized ratio (INR) (Burlina et al, 2006; Mustafa and Clarke, 2006; Ihara et al, 2013; Gallagher et al, 2014). Among female study subjects who did not receive liver transplant, two with neonatal onset OTCD, 25 with late onset OTCD and 12 asymptomatic participants had mildly elevated plasma ALT when they joined the study (Fig.…”

Section: Genotype and Phenotype Of Patients In The Longitudinal Studymentioning

confidence: 99%

Genotype–Phenotype Correlations in Ornithine Transcarbamylase Deficiency: A Mutation Update

Caldovic

Abdikarim

Narain

et al. 2015

Journal of Genetics and Genomics

131

137

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Ornithine transcarbamylase (OTC) deficiency is an X-linked trait that accounts for nearly half of all inherited disorders of the urea cycle. OTC is one of the enzymes common to both the urea cycle and the bacterial arginine biosynthesis pathway; however, the role of OTC has changed over evolution. For animals with a urea cycle, defects in OTC can trigger hyperammonemic episodes that can lead to brain damage and death. This is the fifth mutation update for human OTC with previous updates reported in 1993, 1995, 2002, and 2006. In the 2006 update, 341 mutations were reported. This current update contains 417 disease-causing mutations, and also is the first report of this series to incorporate information about natural variation of the OTC gene in the general population through examination of publically available genomic data and examination of phenotype/genotype correlations from patients participating in the Urea Cycle Disorders Consortium Longitudinal Study and the first to evaluate the suitability of systematic computational approaches to predict severity of disease associated with different types of OTC mutations.

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Significant Hepatic Involvement in Patients with Ornithine Transcarbamylase Deficiency

Cited by 57 publications

References 58 publications

A longitudinal study of urea cycle disorders

A longitudinal study of urea cycle disorders

Coagulation Disturbances in Patients with Argininemia

Genotype–Phenotype Correlations in Ornithine Transcarbamylase Deficiency: A Mutation Update

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