A non-interventional observational study to identify and validate clinical outcome assessments for adults with phenylketonuria for use in clinical trials

Burton, Barbara K.; Skalicky, Anne; Baerwald, Christoph; Bilder, Deborah A.; Harding, Cary O.; Ilan, Aaron B.; Jurecki, Elaina; Longo, Nicola; Madden, David T.; Sivri, Hatice Serap; Wilcox, Gisela; Thomas, Janet A.; Delaney, Kathleen

doi:10.1016/j.ymgmr.2021.100810

Cited by 3 publications

(4 citation statements)

References 35 publications

(54 reference statements)

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“…When this initial screening is positive, the entire BRIEF should be completed to understand the spectrum and severity of deficits in executive functioning. It is recognized that results obtained on screening tools, such as the BRIEF, may reflect the impact of limited self-awareness, which can be present in some patients with PKU due to the neurocognitive impairments, complicating self-assessment of symptoms [69,70]. In such situations, alternate versions of the BRIEF are available, permitting perspectives from another informant (e.g., spouse, parent or caregiver), while rating scales could also be combined with more objective performancebased tasks.…”

Section: %mentioning

confidence: 99%

Management of early treated adolescents and young adults with phenylketonuria: Development of international consensus recommendations using a modified Delphi approach

Burton

Hermida

Bélanger-Quintana

et al. 2022

Molecular Genetics and Metabolism

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confidence: 99%

Management of early treated adolescents and young adults with phenylketonuria: Development of international consensus recommendations using a modified Delphi approach

Burton

Hermida

Bélanger-Quintana

et al. 2022

Molecular Genetics and Metabolism

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“…Unaffected individuals may sometimes more accurately reflect the impact of a disease and its treatment due to adaptation of patients to a particular health state [ 102 ]. In PKU, QoL assessments are further complicated by the fact that elevated blood Phe concentrations can lead to clouded judgement, hampering self-evaluation of the impact of PKU and its management on a patient’s QoL [ 26 , 103 ]. Similar to other clinical outcome assessments, generic QoL measurement tools have limited validity in PKU due to the lack of sensitivity to assess the impact of problems specifically encountered by patients with PKU [ 81 , 82 , 103 , 104 ].…”

Section: Resultsmentioning

confidence: 99%

“…In PKU, QoL assessments are further complicated by the fact that elevated blood Phe concentrations can lead to clouded judgement, hampering self-evaluation of the impact of PKU and its management on a patient’s QoL [ 26 , 103 ]. Similar to other clinical outcome assessments, generic QoL measurement tools have limited validity in PKU due to the lack of sensitivity to assess the impact of problems specifically encountered by patients with PKU [ 81 , 82 , 103 , 104 ]. When applying a PKU-specific QoL questionnaire that considered the burden of diet among other PKU-specific QoL domains, the highest impact scores were indeed related to the emotional impact of PKU and its disease management [ 81 , 82 ].…”

Section: Resultsmentioning

confidence: 99%

Expert Consensus on the Long-Term Effectiveness of Medical Nutrition Therapy and Its Impact on the Outcomes of Adults with Phenylketonuria

Rocha,

Ahring,

Bausell

et al. 2023

Nutrients

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Many adults with phenylketonuria (PKU) rely on medical nutrition therapy (MNT; low phenylalanine (Phe) diet with protein substitutes/medical foods) to maintain blood Phe concentrations within recommended ranges and prevent PKU-associated comorbidities. Despite disease detection through newborn screening and introduction of MNT as early as birth, adherence to MNT often deteriorates from childhood onwards, complicating the assessment of its effectiveness in the long term. Via a modified Delphi process, consensus (≥70% agreement) was sought on 19 statements among an international, multidisciplinary 13-member expert panel. After three iterative voting rounds, the panel achieved consensus on 17 statements related to the limitations of the long-term effectiveness of MNT (7), the burden of long-term reliance on MNT (4), and its potential long-term detrimental health effects (6). According to the expert panel, the effectiveness of MNT is limited in the long term, is associated with a high treatment burden, and demonstrates that adults with PKU are often unable to achieve metabolic control through dietary management alone, creating an unmet need in the adult PKU population.

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“…Regarding examinations, it should be noted that there is a lack of validated screening tools for the adult population. In addition, AwPKU who have been exposed to high blood Phe often experience impairment in neurocognition that can further complicate the completion of self-assessments [82]. Therefore, it is recommended to combine these assessments with more objective performancebased tasks, such as the index finger tapping rate and Archimedes spiral [83].…”

Section: Discussionmentioning

confidence: 99%

Characterisation and differential diagnosis of neurological complications in adults with phenylketonuria: literature review and expert opinion

et al. 2023

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Objective Phenylketonuria (PKU) is a rare inherited metabolic disorder characterised by elevated phenylalanine (Phe) concentrations that can exert neurotoxic effects if untreated or upon treatment discontinuation. This systematic review supported by expert opinion aims to raise awareness among the neurological community on neurological complications experienced by adults with PKU (AwPKU). Methods The PubMed database was searched for articles on neurological signs and symptoms in AwPKU published before March 2022. In addition, two virtual advisory boards were held with a panel of seven neurologists and two metabolic physicians from Germany and Austria. Findings are supported by three illustrative patient cases. Results Thirty-nine articles were included. Despite early diagnosis and treatment, neurological signs and symptoms (e.g. ataxia, brisk tendon reflexes, tremor, visual impairment) can emerge in adulthood, especially if treatment has been discontinued after childhood. In PKU, late-onset neurological deficits often co-occur with cognitive impairment and psychiatric symptoms, all of which can be completely or partially reversed through resumption of treatment. Conclusion Ideally, neurologists should be part of the PKU multidisciplinary team, either to bring lost to follow-up patients back to clinic or to manage symptoms in referred patients, considering that symptoms are often reversible upon regaining metabolic control. The current findings have been combined in a leaflet that will be disseminated among neurologists in Germany and Austria to create awareness.

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A non-interventional observational study to identify and validate clinical outcome assessments for adults with phenylketonuria for use in clinical trials

Cited by 3 publications

References 35 publications

Management of early treated adolescents and young adults with phenylketonuria: Development of international consensus recommendations using a modified Delphi approach

Management of early treated adolescents and young adults with phenylketonuria: Development of international consensus recommendations using a modified Delphi approach

Expert Consensus on the Long-Term Effectiveness of Medical Nutrition Therapy and Its Impact on the Outcomes of Adults with Phenylketonuria

Characterisation and differential diagnosis of neurological complications in adults with phenylketonuria: literature review and expert opinion

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