Switch from Sodium Phenylbutyrate to Glycerol Phenylbutyrate Improved Metabolic Stability in an Adolescent with Ornithine Transcarbamylase Deficiency

Laemmle, Alexander; Stricker, Tamar; Häberle, Johannes

doi:10.1007/8904_2016_551

Cited by 7 publications

(6 citation statements)

References 16 publications

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“…Therefore, our experience suggests that GPB reduced HAC, which improves metabolic profile. This is consistent with the clinical experience of Leamle et al, with an adolescent suffering from ornithine transcarbamylase deficiency who underwent a significant reduction in ammonia and glutamine levels in plasma and an improved metabolic stability (from 8.7 hospitalizations per year to one hospitalization in seven months) after switching to GPB [ 20 ].…”

Section: Discussionsupporting

confidence: 89%

“…However, fasting glutamine correlated weakly with daily glutamine exposure and was not a significant HAC predictor [ 30 ]. In clinical practice, Yeo et al established that glutamine levels were broadly unchanged after the switch [ 21 ]; however, plasma glutamine levels for the unstable patient reported by Laemle et al decreased and were almost maintained within the reference range after starting GPB treatment [ 20 ]. In our experience, glutamine levels decreased with GPB treatment, and were higher in patients with HAC.…”

Section: Discussionmentioning

confidence: 99%

“…Although research with GPB has produced the largest amount of controlled study data in UCD patients to date, there are limited data on chronic GPB therapy in clinical practice [ 20 , 21 ]. The primary objective of this study was to analyze the efficacy and safety of GPB in clinical practice in Spanish UCD patients switching from another ammonia scavenger, during the first year of treatment.…”

Section: Introductionmentioning

confidence: 99%

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Switching to Glycerol Phenylbutyrate in 48 Patients with Urea Cycle Disorders: Clinical Experience in Spain

Martín‐Hernández

Quijada‐Fraile

Correcher³

et al. 2022

JCM

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Background and objectives: Glycerol phenylbutyrate (GPB) has demonstrated safety and efficacy in patients with urea cycle disorders (UCDs) by means of its clinical trial program, but there are limited data in clinical practice. In order to analyze the efficacy and safety of GPB in clinical practice, here we present a national Spanish experience after direct switching from another nitrogen scavenger to GPB. Methods: This observational, retrospective, multicenter study was performed in 48 UCD patients (age 11.7 ± 8.2 years) switching to GPB in 13 centers from nine Spanish regions. Clinical, biochemical, and nutritional data were collected at three different times: prior to GPB introduction, at first follow-up assessment, and after one year of GPB treatment. Number of related adverse effects and hyperammonemic crisis 12 months before and after GPB introduction were recorded. Results: GPB was administered at a 247.8 ± 102.1 mg/kg/day dose, compared to 262.6 ± 126.1 mg/kg/day of previous scavenger (46/48 Na-phenylbutyrate). At first follow-up (79 ± 59 days), a statistically significant reduction in ammonia (from 40.2 ± 17.3 to 32.6 ± 13.9 μmol/L, p < 0.001) and glutamine levels (from 791.4 ± 289.8 to 648.6 ± 247.41 μmol/L, p < 0.001) was observed. After one year of GPB treatment (411 ± 92 days), we observed an improved metabolic control (maintenance of ammonia and glutamine reduction, with improved branched chain amino acids profile), and a reduction in hyperammonemic crisis rate (from 0.3 ± 0.7 to less than 0.1 ± 0.3 crisis/patients/year, p = 0.02) and related adverse effects (RAE, from 0.5 to less than 0.1 RAEs/patients/year p < 0.001). Conclusions: This study demonstrates the safety of direct switching from other nitrogen scavengers to GPB in clinical practice, which improves efficacy, metabolic control, and RAE compared to previous treatments.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Switching to Glycerol Phenylbutyrate in 48 Patients with Urea Cycle Disorders: Clinical Experience in Spain

Martín‐Hernández

Quijada‐Fraile

Correcher³

et al. 2022

JCM

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“…GPB has recently become a widely available pharmacological treatment for patients with UCDs. Beside its efficacy in lowering ammonia levels 3 and promoting metabolic stability, 4 its better taste and easier administration method compared with NaPBA are important advantages especially for the treatment of pediatric patients. Yeowell et al have recently performed a study to assess the burden of pharmacological treatment and the effects of the transition to GPB on health‐related quality of life 5 .…”

Section: Discussionmentioning

confidence: 99%

Severe loss of appetite and refusal to eat as severe side effect of glycerol phenylbutyrate

2022

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Glycerol phenylbutyrate (GPB) is an ammonia scavenger drug commonly used in the therapy of patients with urea cycle defects. Reported side effects include body odor, abdominal pain, nausea, burning sensation in mouth, vomiting, and heartburn. We report on a 3‐year‐old late diagnosed female patient with ornithine transcarbamylase deficiency that experienced severe loss of appetite under treatment with GBP. Due to catabolism (calory intake about 400 kcal/day) and the associated risk of metabolic decompensation, GBP treatment was discontinued. Her appetite and eating behavior normalized within 1 day after discontinuation of GBP and switch to sodium benzoate. Our case demonstrates that GBP can cause severe loss of appetite that may put patients at risk of metabolic decompensation and require discontinuation of therapy.

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“…Finally, the patient successfully received a liver transplant at 15 years of age. Details of the years before liver transplantation were published elsewhere [14]. .…”

Section: Presentation Of the Casementioning

confidence: 99%

Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder

Mourad

Häberle

Whitehead

et al. 2016

IJNS

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Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes, cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological effects include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of the plasma ammonia level at presentation and duration of a hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days of life with plasma ammonia and glutamine of 677 and 4024 micromol/L respectively, and was found to have a missense mutation in Exon 4 (p. R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. Despite compliance, he suffered recurrent acute hyperammonemic episodes triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI-based disease biomarkers.

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Switch from Sodium Phenylbutyrate to Glycerol Phenylbutyrate Improved Metabolic Stability in an Adolescent with Ornithine Transcarbamylase Deficiency

Cited by 7 publications

References 16 publications

Switching to Glycerol Phenylbutyrate in 48 Patients with Urea Cycle Disorders: Clinical Experience in Spain

Switching to Glycerol Phenylbutyrate in 48 Patients with Urea Cycle Disorders: Clinical Experience in Spain

Severe loss of appetite and refusal to eat as severe side effect of glycerol phenylbutyrate

Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder

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