Browsing by Author "Ammous, Zineb"

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    Lessons learned from 5 years of pegvaliase in US clinics: A case series
    (Elsevier, 2024-12-26) Cooney, Erin; Ammous, Zineb; Bender, Tricia; Clague, Gillian E.; Clifford, Marilyn; Crutcher, Angela; Davis-Keppen, Laura; Havens, Kirsten; Lah, Melissa; Sacharow, Stephanie; Sanchez-Valle, Amarilis; Vucko, Erika; Wardley, Bridget; Wessenberg, Leah; Andersson, Hans C.; Medical and Molecular Genetics, School of Medicine
    Objective: To provide insights and strategies for pegvaliase management in challenging cases with phenylketonuria (PKU) based on the first 5 years of experience with pegvaliase in real-world clinical practice. Methods: Twelve PKU experts gathered during a one-day, in-person meeting to discuss clinical cases illustrating important lessons from their experiences treating patients with pegvaliase in real-world clinical practice. Challenges with pegvaliase experienced prior to and during treatment and corresponding strategies to overcome them were discussed. Results: Twelve cases of adults with PKU (eight females and four males, aged 18 to 68 years) receiving pegvaliase were reviewed and discussed. Challenges of the cases included medical or mental health comorbidities, executive function deficits, challenging social or socioeconomic situations, logistical or geographic barriers, or a combination of these; one was considering pregnancy. Despite challenges, pegvaliase was initiated successfully in most cases. Strategies to overcome barriers included individualized education, including side effect action plans, help from support organizations, collaboration with local providers, and use of telemedicine. Recommendations from the clinicians included that comorbid conditions should be monitored closely after treatment initiation and may require collaboration with other healthcare providers. A collaborative relationship with the clinic, ongoing education, and supportive relatives or friends can help individuals to remain adherent to pegvaliase. Suboptimal adherence may be addressed by a daily reminder system, telemedicine, in-home support, or a modified titration plan. Treated individuals with eating disorders require additional follow-up and support to achieve a healthy relationship with food. In most cases, including late-diagnosed individuals, reduced blood Phe levels resulted in improved PKU-related symptoms, including neurological issues. Conclusion: Experience from the presented cases and 5 years of expert experience with pegvaliase in the real-world setting provide insight and guidance for healthcare professionals initiating and managing pegvaliase treatment in complex PKU cases. These cases demonstrate that, through comprehensive assessment and addressing barriers, pegvaliase treatment can be successful in adults with PKU, regardless of prior treatment success, age, socioeconomic, cognitive, or executive function challenges, as well as in those with comorbidities or considering pregnancy. Ongoing documentation of clinical experience is crucial for advancing the management of individuals receiving this treatment.
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    Rapid quantification of underivatized alloisoleucine and argininosuccinate using mixed-mode chromatography with tandem mass spectrometry
    (Elsevier, 2019-10) Griffin, Chandler; Ammous, Zineb; Vance, Gail H.; Graham, Brett H.; Miller, Marcus J.; Medical and Molecular Genetics, School of Medicine
    Plasma elevations of the amino acids alloisoleucine and argininosuccinic acid (ASA) are pathognomonic for maple syrup urine disease and argininosuccinate lyase deficiency, respectively. Reliable detection of these biomarkers is typically achieved using methods with tedious sample preparations or long chromatographic separations, and many published amino acid assays report poor specificity and/or sensitivity for one or both of these compounds. This report describes a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method that provides rapid quantification of alloisoleucine and ASA in human plasma. The basis of this method is a mixed-mode solid phase separation that achieves baseline resolution of alloisoleucine from isobaric interferents without the use of derivatization or ion pairing agents. The inject-to-inject time is 6 min including elution, column washing and re-equilibration. Validation studies demonstrate excellent limits of quantification (1 μmol/L), linearity (r = 0.999 from 1 to 250 μmol/L), accuracy (bias = −3.8% and −10.1%), and inter-assay imprecision (CV < 8.06%) for plasma analyses. Data from long-term clinical application confirms chromatographic consistency equivalent to more traditional reversed-phase or HILIC based columns. Additional matrix studies indicate low suppression (<10%) for a wide range of amino acids and compatibility with other matrixes such as blood spot analyses. Finally, analysis of our first 257 clinical specimens demonstrates high analytic specificity and sensitivity, allowing the detection of subtle but clinically relevant elevations of alloisoleucine and ASA that may be missed by other less sensitive methods. In conclusion, the novel LC-MS/MS method reported here overcomes a number of the challenges associated with alloisoleucine and ASA quantification. Combining this approach with published incomplete amino acid quantification methods allows, for the first time, a rapid and comprehensive LC-MS/MS analysis of underivatized amino acids without the use of ion pairing agents.