Molecular genetics of PKU in Poland and potential impact of mutations on BH4 responsiveness

Tetrahydrobiopterin (BH4) has been recently approved as a treatment of patients with phenylketonuria. However, as a confirmation of BH4-responsiveness, it might require a very expensive trial treatment with BH4 or prolonged BH4-loading procedures. The selection of patients eligible for BH4-therapy by means of genotyping of the PAH gene mutations may be recommended as a complementary approach. A population-wide genotyping study was carried out in 1286 Polish phenyloketonuria-patients. The aim was to estimate the BH4 demand and to cover prospectively the treatment by a National Health Fund. A total of 95 types of mutations were identified. Genetic variants corresponding with probable BH4-responsiveness were found in 28.2% of cases. However, patients with mild or classical phenylketonuria who require continuous treatment accounted for 11.4% of the studied population only. Analysis of the published data shows similar percentage of the "BH4-responsive" variants of a PAH gene in patients from other countries of Eastern Europe. Therefore, it can be concluded, that the proportion of phenylketonuria-patients who could benefit from the use of BH4 reaches approximately 10% in the entire region

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

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

Deficiency of long-chain polyunsaturated fatty acids in phenylketonuria: a cross-sectional study

The etiology of altered blood fatty acid (FA) profile in phenylketonuria (PKU) is understood only partially. We aimed to determine whether FAs deficiency is dependent on the diet or metabolic disturbances. The study comprised 40 PKU patients (20 female, 20 male; aged 11 to 35 years; 12 children and 28 adults) and 40 healthy subjects (HS; 20 female, 20 male, aged 18 to 33 years). We assessed the profile of FAs (gas chromatography/mass spectrometry) and analyzed the 72-hour dietary recalls. The amount of C14:0, C16:0 and C16:1n-7, C18:1n-9 did not differ between the analyzed groups. The percentage of C18:0 was higher, while C20:3n-9, C18:2n-6, C20:2n-6, C20:4n-6, C22:4n-6, C22:5n-6 and C22:6n-3 was lower in PKU than in HS. However, C18:3n-6, C18:3n-3 and n-6/n-3 ratio were higher in PKU patients. The C20:4n-6/C20:3n-6 ratio (reaction catalyzed by Δ5-desaturase), the C22:5n-6/C22:4n-6 and the C22:6n-3/C22:5n-3 ratio (both reactions catalyzed by Δ6 desaturase) were significantly lower in PKU patients. Therefore, the deficiency of long-chain polyunsaturated fatty acids in PKU patients may result not only from inadequate supply but also from metabolic disturbances

Vitamin K Status in Adherent and Non-Adherent Patients with Phenylketonuria: A Cross-Sectional Study

This is the first study to evaluate vitamin K status in relation to dietary intake and phenylalanine dietary compliance in patients with phenylketonuria (PKU). The dietary and PKU formula intake of vitamin K was calculated in 34 PKU patients, with vitamin K status determined by the measurement of prothrombin induced by vitamin K absence (PIVKA-II). Blood phenylalanine concentrations in the preceding 12 months were considered. There were significantly more phenylalanine results exceeding 6 mg/dL in patients with normal PIVKA-II concentrations than in those with abnormal PIVKA-II levels (p = 0.035). Similarly, a higher total intake of vitamin K and dietary vitamin intake expressed as μg/day (p = 0.033 for both) and %RDA (p = 0.0002 and p = 0.003, respectively) was observed in patients with normal PIVKA-II levels. Abnormal PIVKA-II concentrations were associated with a lower OR (0.1607; 95%CI: 0.0273–0.9445, p = 0.043) of having a median phenylalanine concentration higher than 6 mg/dL. In conclusion, vitamin K deficiency is not uncommon in phenylketonuria and may also occur in patients with adequate vitamin K intake. PKU patients with better dietary compliance have a higher risk of vitamin K deficiency. The present findings highlight the need for further studies to re-evaluate dietary recommendations regarding vitamin K intake, both concerning formula-based and dietary consumption of natural products

Professional activity, gender and disease-related emotions: The impact on parents' experiences in caring for children with phenylketonuria

Introduction: Clinical management of rare diseases often fails to acknowledge the challenges faced by caregivers. Whilst management of phenylketonuria (PKU) may not be considered as dire as other conditions, most studies primarily concentrate on clinical issues, dietary adherence, or the quality of life of the PKU patients, leaving caregivers in the background. The aim of the study was to evaluate the psychosocial effects of PKU on family caregivers. Methods: Between October 30th, 2022 and February 28th, 2023, we collected data from caregivers of children with PKU using an anonymous, self-administered, computer-assisted online questionnaire. The survey was distributed among to patients during their regular visits to five Polish PKU treatment centers. Results: A total of 159 Polish caregivers of children with PKU completed the survey. This research shows that while women caregivers were more likely to be unemployed due to their responsibilities for childcare (50.3% compared to 0% for men), and men caregivers were more likely to be employed full-time (93.8% compared to 40.6% for women), the former reported higher emotional engagement in caregiving (88.1% vs 56.3% respectively). Significantly, unemployed mothers reported higher levels of loneliness, helplessness, and emotional control problems, and lacked psychological/emotional support more often than employed mothers. This research also shows a statistically significant positive correlation between mothers' education level and financial situation (p < 0.05) and education level and professional activity (p < 0.01). Additionally, a significant positive correlation was found between perceived financial situation and feeling of happiness (p < 0.001), and between financial situation and professional activity (p < 0.001). Finally, a significant positive correlation was observed between feeling of happiness and professional activity (p < 0.05). Conclusions: According to our findings, there is a link between subjective happiness, financial situation, and professional activity among female caregivers. The relationship between these factors goes beyond just the income earned from work. The results of our study imply that there could even be a therapeutic advantage for working mothers. It is crucial to recognize the emotional difficulties that employed mothers may experience while taking care of a child with PKU, and to provide them with the necessary assistance and resources to meet their needs. Additionally, our results may provide a foundation for redefining the support system for caregivers in Poland

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

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