A retrospective study on disease management in children and adolescents with phenylketonuria during the Covid-19 pandemic lockdown in Austria

Marion Herle,Johannes Spenger,Joachim Zobel,Dorothea Möslinger,Michaela Brunner-Krainz,Barbara Plecko,Sabine Scholl-Bürgi,Martina Huemer,Saskia B Wortmann,Bernadette Goeschl,Daniela Karall

doi:10.1186/s13023-021-01996-x

Abstract

BackgroundIn classical phenylketonuria (PKU) phenylalanine (Phe) accumulates due to functional impairment of the enzyme phenylalanine hydroxylase caused by pathogenic variants in the PAH gene. PKU treatment prevents severe cognitive impairment. Blood Phe concentration is the main biochemical monitoring parameter. Between appointments and venous blood sampling, Austrian PKU patients send dried blood spots (DBS) for Phe measurements to their centre. Coronavirus disease-19 (COVID-19), caused by the SARS CoV-2 virus, was classified as a pandemic by the World Health Organization in March 2020. In Austria, two nationwide lockdowns were installed during the first and second pandemic wave with variable regional and national restrictions in between. This retrospective questionnaire study compared the frequency of Phe measurements and Phe concentrations during lockdown with the respective period of the previous year in children and adolescents with PKU and explored potential influencing factors.Results77 patients (30 female, 47 male; mean age 12.4 [8–19] years in 2020) from five centres were included. The decline of venous samples taken on appointments in 2020 did not reach significance but the number of patients with none or only one DBS tripled from 4 (5.2%) in 2019 to 12 (15.6%) in 2020. Significantly more patients had a decline than a rise in the number of DBS sent in between 2019 and 2020 (p < 0.001; Chi2 = 14.79). Especially patients ≥ 16 years sent significantly less DBS in 2020 (T = 156, p = 0.02, r = 0.49). In patients who adhered to DBS measurements, Phe concentrations remained stable. Male or female sex and dietary only versus dietary plus sapropterin treatment did not influence frequency of measurements and median Phe.ConclusionDuring the COVID pandemic, the number of PKU patients who stopped sending DBS to their metabolic centre increased significantly, especially among those older than 16 years. Those who kept up sending DBS maintained stable Phe concentrations. Our follow-up system, which is based on DBS sent in by patients to trigger communication with the metabolic team served adherent patients well. It failed, however, to actively retrieve patients who stopped or reduced Phe measurements.

Highlights

In classical phenylketonuria (PKU) phenylalanine (Phe) accumulates due to functional impairment of the enzyme phenylalanine hydroxylase caused by pathogenic variants in the PAH gene
Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism in which the enzyme phenylalanine hydroxylase that metabolises Phe to tyrosine is functionally impaired due to variants in the PAH gene [1, 2]
Metabolic teams of five metabolic centres in Austria in which approximately 90% of the country’s paediatric PKU patients are followed answered survey questions on sex, year of birth and treatment, number of Phe measurements, Phe concentrations from dried blood spots (DBS) sent from home, number of regular metabolic clinic visits and Phe concentrations from venous samples taken on these occasions, and the number of telemedicine consultations in their patients with classical PKU

Summary

Introduction

In classical phenylketonuria (PKU) phenylalanine (Phe) accumulates due to functional impairment of the enzyme phenylalanine hydroxylase caused by pathogenic variants in the PAH gene. In Austria, two nationwide lockdowns were installed during the first and second pandemic wave with variable regional and national restrictions in between This retrospective questionnaire study compared the frequency of Phe measurements and Phe concentrations during lockdown with the respective period of the previous year in children and adolescents with PKU and explored potential influencing factors. Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism in which the enzyme phenylalanine hydroxylase that metabolises Phe to tyrosine is functionally impaired due to variants in the PAH gene [1, 2]. Classical PKU leads to severe, early cognitive impairment caused by Phe neurotoxicity. Phe concentration is the main biochemical monitoring parameter [1,2,3]

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Conclusion