Impact of the COVID-19 Era on Phenylalanine Levels and Classical Phenylketonuria Patients Follow-Up: A Retrospective Analysis

Year 2024, Articles Online First, 1 - 5

Ayca Burcu Kahraman , Yılmaz Yıldız , Neslihan Nisa Geçici , Kısmet Çıkı , İzzet Erdal , Halil Tuna Akar , Ali Dursun , Ayşegül Tokatli , Serap Sivri

https://doi.org/10.12956/tchd.1537456

Abstract

Objective: Phenylketonuria is a metabolic disorder resulting from mutations in the PAH gene, causing elevated blood phenylalanine (Phe) levels which can lead to severe neurological damage if untreated. The primary treatment is a lifelong low-protein diet with amino acid substitutes and micronutrient supplements. During the COVID-19 pandemic, classical phenylketonuria (PKU) patients faced significant challenges, including restricted access to routine care like clinical visits and metabolic control monitoring. The aim of the this study was to examine the disruptions in outpatient visits, the variances in pre- and post-pandemic Phe levels, and clinical severity among patients who contracted COVID-19.

Material and Methods: Starting from the pandemic date of March 11, 2020, demographic data, laboratory characteristics, and details about COVID-19 infection were retrospectively reviewed for classical PKU patients with accessible electronic records from March 2018 to March 2022.

Results: When the median blood Phe levels before and after the pandemic were compared, a significant difference was found. We observed that adult patients diagnosed with classical PKU often defaulted on their follow-up appointments.

Conclusion: The COVID-19 pandemic significantly disrupted the follow-up and management of classical PKU patients. However, no severe COVID-19 cases were reported among this population, suggesting they did not face an increased risk from the infection. This study emphasizes the critical need to develop robust strategies for patient engagement and follow-up, especially for adult classical PKU patients who are at risk of discontinuing routine care.

Keywords

Classical phenylketonuria, COVID-19, Phenylalanine levels, SARS-CoV-2

Ethical Statement

This study received approval from the Hacettepe University Ethics Committee for Non-Interventional Clinical Studies (GO22/176, 2022/08–23).

Supporting Institution

The authors received no financial support for the research.

Project Number

GO22/176

COVİD-19 Döneminin Fenilalanin Düzeyleri ve Klasik Fenilketonüri Hastalarının Takibi Üzerindeki Etkisi: Retrospektif Bir Analiz

Abstract

Amaç: Fenilketonüri, PAH genindeki mutasyonlardan kaynaklanan ve tedavi edilmediği takdirde ciddi nörolojik hasara yol açabilecek yüksek kan fenilalanin (Phe) seviyelerine neden olan bir metabolik bozukluktur. Birincil tedavi, ömür boyu düşük proteinli diyet ve amino asit ikameleri ile mikro besin takviyeleridir. COVİD-19 pandemisi sırasında, klasik fenilketonüri (PKU) hastaları, klinik ziyaretler ve metabolik kontrol izlemeleri gibi rutin bakıma erişimde önemli zorluklarla karşılaştı. Bu çalışmanın amacı, ayakta hasta ziyaretlerindeki aksaklıkları, pandemi öncesi ve sonrası Phe seviyelerindeki farklılıkları ve COVİD-19’a yakalanan hastalar arasındaki klinik şiddeti incelemekti.

Gereç ve Yöntemler: Pandemi başlangıç tarihi olan 11 Mart 2020’den itibaren, Mart 2018’den Mart 2022’ye kadar elektronik kayıtlara erişilebilen klasik PKU hastaları için demografik veriler, laboratuvar özellikleri ve COVİD-19 enfeksiyonu ile ilgili detaylar retrospektif olarak incelendi.

Bulgular: Pandemi öncesi ve sonrası medyan kan Phe seviyeleri karşılaştırıldığında, anlamlı bir fark bulundu. Klasik PKU tanısı alan yetişkin hastaların takip randevularını sıklıkla aksattıkları gözlemlendi.

Sonuç: COVİD-19 pandemisi, klasik PKU hastalarının takibi ve yönetimini önemli ölçüde aksattı. Bununla birlikte, bu popülasyon arasında ciddi COVİD-19 vakaları bildirilmemiştir, bu da enfeksiyon açısından artmış bir riskle karşı karşıya olmadıklarını düşündürmektedir. Bu çalışma, özellikle rutin bakımı aksatma riski taşıyan yetişkin klasik PKU hastaları için, hasta katılımı ve takip konusunda sağlam stratejiler geliştirilmesi gerekliliğini vurgulamaktadır.

Keywords

Klasik fenilketonüri, COVİD-19, Fenilalanin seviyeleri, SARS-CoV-2

Project Number

GO22/176

References

• Van Spronsen F, Huijbregts S, Bosch A, Leuzzi V. Cognitive, neurophysiological, neurological and psychosocial outcomes in early-treated PKU-patients: a start toward standardized outcome measurement across development. Mol Genet Metab 2011;104:S45-S51.
• Homaei SC, Barone H, Kleppe R, Betari N, Reif A, Haavik J. ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications. Neurosci Biobehav Rev 2022;132:838-56.
• Özalp I, Coşkun T, Ceyhan M, Tokol S, Oran O, Erdem G, et al. Incidence of Phenylketonuria and Hyperphenylalaninaemia in a Sample of the Turkish Newborn Population. in: Addison, GM, Harkness RA, Isherwood DM, Pollitt RJ. (eds) Practical Developments in Inherited Metabolic Disease: DNA Analysis, Phenylketonuria and Screening for Congenital Adrenal Hyperplasia. Springer 1st ed 1986:237-39.
• Akar H, Karaboncuk Y, Çıkı K, Kahraman A, Erdal İ, Coşkun T, et al. COVID-19-related anxiety in phenylketonuria patients. Turk J Pediatr 2021;63:790-800.
• Coşkun T, Çoker M, Mungan NÖ, Özel HG, Sivri HS. Recommendations on phenylketonuria in Turkey. Turk J Pediatr 2022;64:413-34.
• Chiesa A, Spécola N, Poubel M, Vela-Amieva M, Jurecki E, Vilela DR, et al. Adherence to PKU guidelines among patients with phenylketonuria: A cross-sectional national multicenter survey-based study in Argentina, Brazil, and Mexico. Mol Genet Metab Rep 2024;38:101026.
• Berry SA, Brown C, Grant M, Greene CL, Jurecki E, Koch J, et al. Newborn screening 50 years later: access issues faced by adults with PKU. Genet Med 2013;15:591-9.
• Walkowiak D, Mikołuć B, Mozrzymas R, Kałużny Ł, Didycz B, Jaglowska J, et al. The impact of the First 2020 COVID-19 Lockdown on the metabolic control of patients with Phenylketonuria. Nutrients 2021;13:2024.
• Herle M, Brunner-Krainz M, Karall D, Goeschl B, Möslinger D, Zobel J, et al. A retrospective study on disease management in children and adolescents with phenylketonuria during the Covid-19 pandemic lockdown in Austria. Orphanet J Rare Dis 2021;16:367.
• Burton BK, Leviton L. Reaching out to the lost generation of adults with early-treated phenylketonuria (PKU). Mol Genet Metab 2010;101:146-8.
• Walkowiak D, Mikołuć B, Mozrzymas R, Kałużny Ł, Didycz B, Korycińska-Chaaban D, et al. The impact of the COVID-19 pandemic on the perception of health and treatment-related issues among patients with Phenylketonuria in Poland—The results of a National Online Survey. Int J Environ Res and Public Health 2021;18:6399.
• Walkowiak D, Mikołuć B, Mozrzymas R, Kałużny Ł, Didycz B, Korycińska-Chaaban D, et al. Phenylketonuria patients’ and their caregivers’ perception of the pandemic lockdown: the results of a National Online Survey. Children 2022;9:131.
• Çelik MY, Canda E, Erdem F, Uçar SK, Çöker M. Impact of the COVID-19 Pandemic on Inherited Metabolic Diseases: Evaluation of Enzyme Replacement Treatment Adherence with Telemedicine. J Pediat Res 2022;9:391-6.
• Cannizzo S, Quoidbach V, Giunti P, Oertel W, Pastores G, Relja M, et al. The COVID-19 pandemic impact on continuity of care provision on rare brain diseases and on ataxias, dystonia and PKU. A scoping review. Orphanet J Rare Dis 2024;19:81.
• Koç Yekedüz M, Doğulu N, Sürücü Kara İ, Öncül Ü, Bakirarar B, Kullu P, et al. Pros and cons of telemedicine for inherited metabolic disorders in a developing country during the COVID-19 pandemic. Telemed J E Health 2022;28:1604-12.
• McBride H, Evans S, Pinto A, Daly A, Ashmore C, Ilgaz F, et al. Patient and carer perceptions of video, telephone and in-person clinics for Phenylketonuria (PKU). Orphanet J Rare Dis 2024;19:303.
• Rovelli V, Zuvadelli J, Ercoli V, Montanari C, Paci S, Dionigi AR, et al. PKU and COVID19: how the pandemic changed metabolic control. Mol Genet Metab Rep 2021;27:100759.
• Zubarioglu T, Hopurcuoglu D, Uygur E, Ahmadzada S, Oge-Enver E, Isat E, et al. The impact of telemedicine for monitoring and treatment of phenylketonuria patients on metabolic outcome during coronavirus disease-19 outbreak. Telemed J E Health 2022;28:258-65.
• Becsei D, Kiss E, Szatmári I, Arató A, Reusz G, Szabó AJ, et al. A retrospective analysis of metabolic control in children with PKU in the COVID-19 era. Mol Genet Metab Rep 2022;32:100897.
• Dessie ZG, Zewotir T. Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423,117 patients. BMC Infect Dis 2021;21:855.