Bridging the gap in access to filter paper monitoring in patients with phenylketonuria - a Medical Nutrition Therapy for Prevention (MNT4P) program initiative

Background: Filter paper (FP) or dried blood spot testing is the preferred method of monitoring blood levels of phenylalanine and tyrosine for patients diagnosed with phenylketonuria (PKU) in the state of Georgia. This cost effective and convenient at-home approach simplifies the nutritional assessment and management of patients with PKU and lessens the burden on patients and caretakers. Emory and a local specialty laboratory had a long-standing contract for FP testing, which included patient insurance and grant billing. When this laboratory abruptly ended FP testing in September 2020, an emergent alternative plan became essential to prevent potential disruptions in patient care while working on a sustainable solution for PKU monitoring, especially given the ongoing COVID-19 pandemic. Method(s): Emory's in-house laboratory was not contracted with outside laboratories to process FP testing and bill insurance. To mitigate any delays in FP testing, the MNT4P program conducted a vendor search and selected ARUP Laboratories to perform PKU FP testing. Eligible patients included those referred, enrolled, and consented to the MNT4P program. To streamline the FP submission process, customized FP cards and business reply envelopes were developed and distributed in collaboration with PerkinElmer, Emory Mail Services and the United States Postal Service. Patient outreach efforts were facilitated through email campaigns, MNT4P website updates, and in collaboration with Georgia PKU Connect. Result(s): 95 patients were referred to MNT4P program for FP paper monitoring. During the 4-month period, a total of 239 FPs were collected from patients with PKU and processed with corresponding results reported to Emory Clinic, allowing registered dietitians to continue nutrition management without disruption. Once the patient-centered business prototype was established, FP testing was successfully transferred from the MNT4P program to Emory's inhouse laboratory. FP testing is now a part of Emory's test catalog, and results are available to providers through electronic health records. Conclusion(s): The MNT4P program successfully worked with Emory's in-house laboratory to develop a sustainable solution for FP monitoring. It prevented interruption in long-term follow up of patients with PKU. MNT4P continues to be the payor of FP tests for uninsured and underinsured patients.Copyright © 2022 Elsevier Inc. All rights reserved.

Development of an overdue outreach program to improve adherence to PKU management

Background: Phenylketonuria (PKU) is an inherited autosomal recessive disorder caused by variants in the PAH gene which encodes for phenylalanine hydroxylase (PAH). PKU, left untreated, can cause intellectual disability, psychiatric symptoms, and behavioral abnormalities. Lifelong management of PKU is challenging, and many adult patients become lost to follow-up, despite recommendations for lifelong management. Method(s): The PKU clinic team is a multidisciplinary team consisting of an APN Director, physician, dieticians, diet tech, genetic counselor, registered nurse, and social worker. After establishing formal guidelines, algorithms were created to determine thresholds for initiating patient outreach based on both age and type of PKU treatment. EMRbased data collection is used to track adherence to both clinic visits and consistent submission of Phe levels. Data was collected and analyzed for roughly 250 PKU patients. Baseline levels for adherence to clinic visits and filter card submission were collected at time of implementation. Data was then reviewed after 18 months, and has been further analyzed for a second 18 months (which correlates with the start of the COVID-19 pandemic) Results: Overall baseline adherence across the population for annual clinic visitswas 72% (144/200). Clinic visit adherence increased to 88% at 18 months, and then was similar at 86% through COVID-19 pandemic. In the adult population, 54% (57/106) were adherent at baseline with clinic follow-up. With implementation compliance increased to 80% initially and was then reported to be 74% during the pandemic. Baseline for all PKU patients showed 81% (161/200) filter card submission within the last 12 months. Submission increased to 91% after 18 months of overdue outreach, and as of October 2021, 85% of all patients had submitted a filter card within the last calendar year. Adult patients specifically showed an increase, with 53% at baseline to 69% after implementation. Conclusion(s): Implementation of an overdue outreach program is successful in re-engaging patients with the PKU clinic and improving adherence to treatment recommendations. We have seen increased patient adherence across all domains and have maintained this improved adherence despite the global COVID-19 pandemic.Copyright © 2022 Elsevier Inc. All rights reserved.

Custom parenteral nutrition for critically ill patients with aminoacidopathies

Background: Nutrition therapy is crucial in the management of aminoacidopathies. The goal during critical illness is to reverse catabolism by providing sufficient energy and non-offending amino acids (AAs). If the patient's condition is unstable, tolerance of adequate enteral nutrition (EN) to promote anabolism may not be feasible. Parental nutrition (PN) may be necessary to meet nutrition goals, however standard preparations of PN are contraindicated. Integrity Compounding Pharmacy [Sandy Springs, GA] offers specialty compounding options tailored to provide PN to critically ill patients with aminoacidopathies void of offending AAs. Method(s): Retrospective chart review was performed. Patient Awas a 4-day old twin female born at 31-weeks gestation with phenylketonuria (PKU) hospitalized for prematurity and respiratory failure. Patient B was a 4-day old female, sibling of patient A, also with PKU hospitalized due to prematurity, respiratory failure and ductal dependent pulmonic stenosis. Patient C was a 26 year old male with maple syrup urine disease (MSUD) admitted for metabolic decompensation and respiratory failure in the setting of novel Covid-19 virus. Patient Dwas an 8 year old female with MSUD presenting with nausea and vomiting in the setting of novel Covid-19 virus. All four patients experienced elevated blood levels of offending AAs and inadequate EN intake. Custom PN from Integrity Compounding Pharmacy was utilized in all four patients ranging from 6 to 11 days. Patient A, B and D received custom PN as sole source nutrition for a period of time while transitioning to EN. Patient C tolerated a small amount of EN as well as custom PN to meet nutrition goals. Result(s): The Integrity custom PN provided appropriate AAs to optimize nutrition until full EN could be tolerated. This essential nutrition therapy helped reverse catabolism, achieve metabolic control and prevent further sequelae. Conclusion(s): Custom PN should be considered in critically ill patients with aminoacidopathies that have significant EN intolerance.Copyright © 2022 Elsevier Inc. All rights reserved.

The effect of the COVID-19 pandemic on newborn hyperphenylalaninemia screening program

Phenylketonuria is an inherited metabolic disease that can be treated if detected early and can easily be screened with phenylalanine as a biomarker. Phenylketonuria is included in the National Neonatal Screening Program. We aimed to investigate the possible effects of the pandemic on phenylketonuria screening in our country during coronavirus disease 2019 (COVID-19) era. We retrospectively evaluated patients who were referred to our center due to elevated blood phenylalanine levels detected by national screening program retrospective- and prospectively within one-year as of 11 March 2020, the date when first COVID-19 case was detected in our country. Multivariate analysis showed birth region and phenylalanine levels to be independently associated with the time period until the first admission to hospital, but none of the parameters were significantly associated with the pandemic. There was no evidence that the COVID-19 pandemic affected the screening of newborn phenylketonuria, however since the data was limited to our center and to draw generalized conclusions larger scaled multicentric studies are needed.

Gut-on-a-chip for disease models.

The intestinal tract is a vital organ responsible for digestion and absorption in the human body and plays an essential role in pathogen invasion. Compared with other traditional models, gut-on-a-chip has many unique advantages, and thereby, it can be considered as a novel model for studying intestinal functions and diseases. Based on the chip design, we can replicate the in vivo microenvironment of the intestine and study the effects of individual variables on the experiment. In recent years, it has been used to study several diseases. To better mimic the intestinal microenvironment, the structure and function of gut-on-a-chip are constantly optimised and improved. Owing to the complexity of the disease mechanism, gut-on-a-chip can be used in conjunction with other organ chips. In this review, we summarise the human intestinal structure and function as well as the development and improvement of gut-on-a-chip. Finally, we present and discuss gut-on-a-chip applications in inflammatory bowel disease (IBD), viral infections and phenylketonuria. Further improvement of the simulation and high throughput of gut-on-a-chip and realisation of personalised treatments are the problems that should be solved for gut-on-a-chip as a disease model.

Starting the conversation on gene therapy for phenylketonuria: Current perspectives of patients, caregivers, and advocates.

Phenylketonuria (PKU) is a rare genetic condition caused by inborn error(s) in the gene for the enzyme phenylalanine hydroxylase. Resulting loss of phenylalanine (Phe) metabolism requires strict dietary therapy and/or medication to prevent toxic accumulation of Phe. Novel investigational therapies, including gene therapies that aim to address underlying causes of PKU, are now entering clinical trials. However, perceptions of this technology in the PKU community have not been assessed. We conducted a qualitative survey recruiting adult patients, caregivers, and patient advocates from the US and 3 EU countries to assess the impact of living with PKU and the perceptions of gene therapy. Telephone interviews were conducted for up to 60 min following a standardized discussion guide. Interviewers classified each participant by their level of knowledge regarding gene therapy as either: low (little or no prior awareness); moderate (awareness of gene therapy as a concept in PKU); or high (working knowledge of gene therapy, e.g., vectors). In total, 33 participants were recruited (patients, n = 24; caregivers, n = 5; advocates, n = 4). The patient sample was well balanced among age groups, sex, and US/EU geographies. The participants' experiences and burden of living with PKU were largely negative, characterized by frustrations with current management consistent with prior reports. Most participants (n = 18/33) were identified as displaying moderate gene-therapy knowledge, 10/33 as displaying high knowledge, and 5/33 as displaying low knowledge. Both positive and negative perceptions were observed; positive perceptions were often linked to "hope" that gene therapy may represent a cure, whereas negative perceptions were linked to the "uncertainty" of outcomes. High knowledge of gene therapy appeared to trend with negative perceptions; 7/10 participants from this group reported high levels of concern over gene therapy. In contrast, participants who displayed low knowledge reported low (n = 3/5) or moderate (n = 2/5) concern, with predominantly positive perceptions. These data highlight the need for education around the theoretical risk:benefit profile of gene therapy. Despite current unknowns around gene therapy, our study demonstrates the important role of healthcare providers as educators who can use available data to provide balanced information to patients and caregivers.

A retrospective analysis of metabolic control in children with PKU in the COVID-19 era.

Background: Patients with phenylketonuria (PKU) must maintain a lifelong natural protein-restricted diet to prevent neuro-cognitive damage. Early diagnosis is established with newborn screening, with diet subsequently controlled by regular phenylalanine (Phe) monitoring. During the COVID-19 pandemic, significant lockdown measures were introduced that may have influenced the above. Aim of our study: To establish whether the diagnosis was delayed in neonates during the pandemic. In addition, metabolic control was further assessed during the COVID-19 pandemic era (CE) compared to the same period a year prior (non-COVID-19 era, NCE). The lockdown periods (LD) were also compared with unrestricted periods (URP). Patients methods: Six neonates born during the CE and eight neonates born during NCE were included in the newborn screening analysis. Seventy-two classical PKU patients aged 2-18 years and categorized as children (2-12 years; 51 patients) and adolescents (>13 years; 21 patients) were included in the metabolic control analysis. The frequency of dried blood spot (DBS) sampling and Phe levels were assessed according to the different periods. Results: There was no diagnostic or therapeutic delay in reaching the recommended Phe range in neonates born during CE compared to those born in NCE (median [interquartile range, IQR]: 23.5 [22.5-24] vs. 22 [18.0-27] days, p = NS). The cumulative DBS sampling frequency in children increased by 9.9% in the CE while no change was noted in the adolescent group. The median Phe level increased significantly in both age groups in the CE, but remained within the recommended target range. During CE, changes in Phe levels differed in the two age groups: children had the highest median Phe in the second lockdown period (LD2), while the adolescents had an increased Phe in URP.There were significant negative correlations between DBS sampling frequencies and Phe levels in both age groups in NCE (children: r - 0.43, p = 0.002; adolescents r = -0.37, p = 0.012), and in adolescents in CE (r = -0.62, p = 0.006). Conclusion: The pandemic did not impact newborn metabolic screening. The increased frequency of DBS sampling in CE and good target Phe levels suggest a better compliance in a very sensitive period. Since many factors may impact metabolic control in the different age groups, further studies are needed to analyse their respective role.

eP276: Development of an overdue outreach program to improve adherence to phenylketonuria management

Introduction: Phenylketonuria (PKU) is an inherited autosomal recessive disorder caused by variants in the PAH gene which encodes for phenylalanine hydroxylase (PAH). PAH deficiency leads to phenylalanine (Phe) accumulation, which untreated can cause intellectual disability, microcephaly, delayed speech, seizures, psychiatric symptoms, and behavioral abnormalities. Early detection of elevated Phe through newborn screening allows for rapid initiation of a Phe-restricted diet to prevent severe neurological outcomes;however, suboptimal Phe control throughout the lifespan is associated with increased rates of psychiatric illness and deficits in executive function even in early treated patients. Lifelong management of PKU is challenging, and it is well documented that many adult patients become lost to follow-up, despite the American College of Medical Genetics recommendation for lifelong management. Here we describe and evaluate efforts to improve follow-up care for patients with PKU of all ages at one center through formalization of clinic guidelines and creation of an overdue outreach program. Methods: The PKU clinic team is a multidisciplinary team consisting of an APN Director, physician, dieticians, diet tech, genetic counselor, registered nurse, and social worker. Regular meetings were scheduled with all clinic staff members to review PKU treatment guidelines, recommended lab monitoring, and visit frequency. After establishing formal guidelines, algorithms were created to determine thresholds for initiating patient outreach based on both age and type of PKU treatment. EMR-based data collection is used to track adherence to both clinic visits and consistent submission of Phe levels. Data was collected and analyzed for Lurie Children’s PKU program, which consists of roughly 250 patients. Baseline levels for adherence to clinic visits and filter card submission were collected at time of implementation. Data was then collected and analyzed initially after 18 months, and has been further analyzed for a second 18 months (which correlates with the start of the COVID-19 pandemic). Results: Overall baseline adherence across the PKU patient population for annual clinic visits was 72% (144/200). Clinic visit adherence increased to 88% at 18 months, and then was essentially unchanged at 86% through COVID-19 pandemic. In the pediatric patient population, annual clinic follow-up adherence was 92% (79/86) at baseline, which increased to 98% with implementation and maintained 98% during the pandemic. In the adult patient population, 54% (57/106) were adherent at baseline with clinic follow-up. With implementation compliance increased to 80% initially and was then reported to be 74% during the pandemic. Baseline for all PKU patients showed 81% (161/200) filter card submission within the last 12 months. Submission increased to 91% after 18 months of overdue outreach, and as of October 2021, 85% of all patients had submitted a filter card within the last calendar year. Adult patients specifically showed an increase, with 53% at baseline to 69% after implementation. Hyperphenylalaninemia (hyperphe) patients over the age of 2 showed an 18% (5/28) submission at baseline. With the overdue outreach program, this increased to 31% of patients initially and has further increased to 39%. Clinic visits for patients greater than 7 years old rose from 13% (3/24) initially to 57% and has further increased to 67%. Conclusion: Implementation of a coordinated overdue outreach program is successful in re-engaging patients with the PKU clinic and improving adherence to treatment recommendations. We have seen increased patient adherence across all domains, and have maintained this improved adherence despite the global COVID-19 pandemic. We believe that integrating overdue outreach guidelines into clinical practice is a replicable model for PKU clinics.

From PKU Online Lessons for Dietetics Students to the PKU Sandwiches Album

The purpose of the manuscript is to present to academic teachers, doctors and nutritionists how practical online classes with dietetics students can be used to develop ready-made tools at work and for the education of phenylketonuria (PKU) patients and their caregivers/parents. During online classes in 2020, as part of the subject—diet therapy of metabolic blocks, 53 students prepared PKU sandwiches at home. Each PKU sandwich has a calculated nutritional value, and phenylalanine exchanger content, but does not include low-protein bread. The selection of a particular type of PKU bread depends solely on the PKU patient, hence it was deliberately not included in the calculations. The sandwiches, made by students and assessed by academic teachers, will be published with the following title “The PKU Sandwiches Album”. The Album with more than 400 colorful pictures of PKU sandwiches, will be expected to inspire patients and help them add appeal to their diet, enriching it with new tastes, at the same time facilitating the memorizing process of ingredients, thanks to visualization and presented calculations, and motivating them to comply with strict dietary recommendation. The same nutritional calculations and ideas for sandwiches, with the use of different bread, e.g., gluten-free, may be useful in other diseases, such as celiac disease.

Phenylketonuria Patients' and Their Caregivers' Perception of the Pandemic Lockdown: The Results of a National Online Survey.

The first pandemic lockdown dramatically impacted many aspects of everyday life, including healthcare systems. The purpose of this study was to identify problems of patients with phenylketonuria (PKU) and their parents/caregivers during that time. We aimed to analyse potential differences in the self-reported compliance and characteristics of contacts with a doctor/dietitian before and during the pandemic lockdown and the perception of access to special food and opinions on remote contacts between a particular group of respondents. All participants (n = 614) were asked to complete an online questionnaire that consisted of 31 questions on pandemic-related events and circumstances which may have directly or indirectly impacted health and treatment. The people who completed the survey were divided into three groups: parents of PKU children (n = 403), parents of PKU adults (n = 58) and PKU patients older than 16 years (n = 153). The differences among the three analysed groups were found in the number of contacts, the way of contacting a doctor/dietitian during the pandemic and satisfaction with remote contact. Caregivers of children with PKU reported better therapy compliance, more frequent contacts with specialists and more satisfaction with remote visits than adult patients. We also observed a relationship between satisfaction from remote contact and self-reported frequency of contacts with a doctor/dietitian, as well as a relationship between satisfaction from remote contact and recommended blood Phe levels reported by both patients and caregivers. Travel time exceeding three hours from the respondents' location to their doctor was associated with higher odds of their recognition of remote contact as a method of PKU treatment only in the group of caregivers. In the caregiver groups, the reported worse access to low-Phe products during the lockdown was linked to the perceived difficulty of maintaining the diet. However, such a relationship was not found among patients. In conclusion, significant differences in the perception of the pandemic lockdown and its impact on health and treatment-related issues were found.

COVID-19-related anxiety in phenylketonuria patients.

BACKGROUND: Phenylketonuria (PKU) is an inherited disorder of amino acid metabolism, the treatment of which often requires a special diet to prevent adverse neuropsychiatric outcomes. In the COVID-19 pandemic, which has had a substantial effect on the whole world since the beginning of 2020, PKU patients represent a vulnerable population because they may be dependent on special nutritional products, have limited access to routine care and display increased levels of anxiety. METHODS: For this reason, an online questionnaire assessing the anxiety levels and various personal opinions and practices regarding the pandemic was sent to the PKU patients managed at our clinic, who were 12 years of age or older. Ninety-eight patients responded to the questionnaire. Median age of the participants was 19 years. RESULTS: Most patients were compliant with the hygiene and social distancing recommendations regarding the spread of COVID-19. Of the patients, 61.2% felt more anxious since the pandemic. The most common concern was the possibility of not being able to obtain special nutritional products (58.2%). Anxiety level was significantly higher in females. CONCLUSIONS: These data suggest that food security is an important issue of concern in PKU patients. In line with the changing world after the pandemic, different strategies should be considered in the management of patients with inborn errors of metabolism, including PKU.

Telehealth and COVID-19: Empowering Standards of Management for Patients Affected by Phenylketonuria and Hyperphenylalaninemia.

Phenylketonuria (PKU) and Hyperphenylalaninemia (HPA) are inborn errors of metabolism (IEM) due to mutations in the PAH gene resulting in increased blood phenylalanine (Phe) concentrations. Depending on the Phe levels, a lifelong dietary intervention may be needed. During the COVID-19 pandemic, finding new strategies to ensure follow-up and metabolic control for such patients became mandatory and telehealth was identified as the most eligible tool to provide care and assistance beyond barriers. The aim of this study was to evaluate how telehealth use may have impacted disease follow-ups. Seven hundred and fifty-five patients affected by PKU/HPA in follow-ups at the Clinical Department of Pediatrics (San Paolo Hospital, ASST Santi Paolo e Carlo, University of Milan, Italy) were included in this study. The data regarding the used telehealth model, type of performed consultations and patients' perspectives were retrospectively collected and analyzed after a one-year experience of implemented follow-ups. The results demonstrated that telehealth seemed to be a useful tool to improve the adherence to treatment and that it could guarantee continuous assistance and care beyond the surrounding epidemiological status. Patients expressed great satisfaction with the offered services and requested that they were implemented in standards of care on a long-term basis. Our results suggested the implementation of telehealth in the management guidelines for PKU/HPA patients.

The Impact of the First 2020 COVID-19 Lockdown on the Metabolic Control of Patients with Phenylketonuria.

The present study assessed patients' metabolic control of phenylketonuria (PKU) during the first 2020 COVID-19 lockdown in Poland. Blood (phenylalanine) Phe results of the tests of 535 patients, performed in 2019 and in the first months of 2020, were analysed. The six-week lockdown period was compared to the preceding six-week period as well as to the two corresponding periods of 2019 (three non-lockdown periods). More patients failed to perform Phe tests in the lockdown period (32.7%) than in non-lockdown periods (15.6%, 15.1%, 17.2%; p < 0.001 for all). The median Phe levels for those patients who performed testing in all the four periods did not differ between periods. However, these patients tended to perform only one test during the lockdown (ORs: 1.43 to 1.60; 95% CI: from 1.01-2.04 to 1.11-2.30, p-value 0.02 to 0.005). Patients who did not take blood during the lockdown (46.7%) performed significantly fewer blood tests in the remaining periods (median : 1 <0-1> vs. 2 <1-4>; p < 0.001). In conclusion, direct assessment of patients' compliance based upon Phe levels during the pandemic lockdown was not possible. Pre-pandemic non-compliant patients frequently failed to perform the test during the lockdown, whereas the previously compliant ones were more likely to perform only one test. This strongly suggests that metabolic control might have worsened.

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.

There is agreement that the pandemic has affected the healthcare system and behaviour of patients. This study aims to identify problems encountered by patients with phenylketonuria (PKU) and their parents/caregivers during the six-week pandemic lockdown in Poland (15 March to 30 April 2020). To determine the factors that influenced health and treatment-related issues, as well as the respondents' perception of the impact of the pandemic, study participants were asked to complete a non-validated online questionnaire comprising 31 questions (including 27 single-choice, two multiple-choice and two open-ended ones). A total of 571 patients or their parents completed the questionnaire, with 9.5% of respondents not performing any blood phenylalanine (Phe) test in the analysed period, 21.3% declaring a blood Phe increase, and 15.3% a decrease. Increased problems in contacting the doctor or dietitian were reported by 26.1% of subjects, whereas 39.3% of them felt restricted access to dietary products. Most (63.4%) participants were satisfied with remote contact with their PKU clinic. Better compliance was associated with higher odds of acceptance of remote contact and of reporting fewer problems with contacting the doctor, and with lower odds of missing Phe testing. Self-reported high stress was associated with higher odds of reporting the limited availability of low-Phe products and Phe-free formulas, as well as with increased Phe concentrations and non-PKU-related health problems. These patients also had poor dietary compliance and experienced more problems in contacting specialists. Health and treatment-related problems experienced during the pandemic lockdown were related to a higher intensity of stress in patient's family and worse therapy compliance before the pandemic. Previous experience of remote visits resulted in a better perception of this method of contact. It seems that this form of communication should be popularized and improved to increase therapy effectiveness in case of different limitations in the future. Special attention should be paid to vulnerable patients who may be at extra risk when the provision of standard care is affected.

PKU and COVID19: How the pandemic changed metabolic control.

BACKGROUND: COVID19 pandemic urged the need to take severe measures for reducing the epidemic spread. Lockdowns were imposed throughout countries and even Inborn errors of metabolism (IEMs) affected patients had to face it and adapt, with management strategies changes coming along. Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism causing, when not treated, blood Phe increases and consequent central nervous system (CNS) damage. Dietary intervention is the main recognized treatment and must be maintained long-life, however adherence is often suboptimal in adulthood. Aim of this study was to evaluate whether and how the pandemic had impacted PKUs metabolic control and what factors may have played a role as potential modifiers. METHODS: Patients ≥4 yo and in follow-up at our Metabolic Clinic were enrolled in this study, divided into subgroups according to age (GROUP A < 12 yo; GROUP B ≥ 12 yo). Videoconsults were conducted on a minimum monthly basis and collected DBS were studied and compared to previous year same time-period in order to evaluate possible changes. RESULTS: 39% of patients (n = 121) increased the number of performed DBS. "Non-compliant" patients were reduced (11-3%) with a - 14% of patients with mean Phe levels >600 umol/l and a - 8% of patients with 100% DBS above same level. GROUP A maintained substantially unchanged metabolic control among two analyzed time-periods. On the contrary, GROUP B demonstrated significant reductions in mean blood Phe concentrations (p < 0.0001) during the pandemic (mean 454 umol/l, SD ± 252, vs. 556.4 umol/l, SD ± 301). DISCUSSION: COVID19 pandemic strongly impacted people's life with lifestyle habits changing consistently. PKU patients had to adapt their dietary restrictions to the new environment they were exposed to and, if younger patients could have been less exposed (meals strictly according to diet plan independently from setting), adolescent and adults strongly reflected the obligation to stay home by showing better metabolic control. Multiple factors could have played a role in that and the availability of teleconsultancy may have contributed allowing easier connections, but our data demonstrate how the pandemic and the environment can strongly impact PKUs adherence to treatment and how removing distance barriers can ameliorate and optimize metabolic compliance.