フェニルケトン尿症

Phenylalanine (Phe) accumulation in blood is a hallmark of phenylketonuria (PKU), a metabolic disorder that requires early diagnosis and lifelong monitoring to prevent irreversible neurological damage. Conventional analytical methods rely on centralized laboratory infrastructure, limiting their use in decentralized and point-of-care (POC) settings. Here, we report an enzymatic electrochemical biosensor based on screen-printed carbon-graphene electrodes modified with gold nanoparticles (AuNPs) and functionalized with phenylalanine dehydrogenase (PheDH). The biosensor exhibited a linear response across physiological and pathological Phe concentrations, with a sensitivity of 13.6 μC (mg dL-1)-1 and a limit of detection of 0.12 mg dL-1. Michaelis-Menten analysis yielded an apparent Km of 1.31 mg dL-1 and a maximum charge (Qmax) of 316 μC, indicating high affinity between the immobilized enzyme and Phe. The platform also enabled quantitative detection in spiked biological matrices, demonstrating its applicability to clinically relevant samples. Bioinformatic and structural analyses revealed that AuNPs promote a favorable enzyme orientation that enhances substrate accessibility and electron transfer. By integrating electrochemical measurements with molecular-level modeling, this work establishes a rational strategy for designing high-performance enzymatic biosensors. The compatibility of the platform with portable electrochemical instrumentation highlights its translational potential for decentralized and self-monitoring applications in PKU management, although further validation with larger clinical sample sets and long-term stability studies is required.

UNLABELLED: Phenylketonuria is an inherited metabolic disorder characterized by impaired phenylalanine (Phe) catabolism and toxic Phe accumulation. Current therapies are limited by poor long-term adherence, high cost, and biosafety concerns associated with existing or emerging approaches. Here, a non-replicative yet metabolically active platform was developed using anucleate minicells derived from Escherichia coli Nissle 1917 (EcN). A dual phenylalanine degradation system was introduced to engineer these minicells into synthetic microreactors, designated PCB101. In vitro, PCB101 degraded 10 mM Phe within 1.5 h. In a murine hyperphenylalaninemia model, intravenous injection of PCB101 (109 cells/mL) reduced plasma Phe by 87.5%, and oral administration (1010 cells/mL) achieved a 66% reduction in a dose-dependent manner. These results demonstrate that EcN-derived minicells provide a controllable and biosafe chassis for efficient Phe degradation both in vitro and in vivo, supporting their potential applicability in biotherapeutic strategies requiring stable dosing and prevention of microbial proliferation. IMPORTANCE: Engineered microbial systems are widely applied to perform defined metabolic functions, yet most designs rely on viable and replicating cells, intrinsically coupling functional output to population expansion. This growth-dependent paradigm complicates dose stability and raises biosafety concerns in practical applications. This study demonstrates that anucleate minicells derived from Escherichia coli Nissle 1917 retain translational and metabolic activity despite lacking chromosomal DNA and replicative capacity. By incorporating a dual phenylalanine degradation pathway, the engineered minicells efficiently reduced phenylalanine both in vitro and in vivo. This study illustrates that metabolic function can be preserved independently of cell division, providing a controllable microbial platform for applications requiring stable functional output without population expansion. This work expands the conceptual framework for non-replicative microbial systems in applied microbiology.

BACKGROUND: Phenylketonuria (PKU) is a rare inherited metabolic disorder requiring lifelong treatment. While early diagnosis and dietary management have substantially improved neurocognitive outcomes, less is known about how PKU affects sexual life, intimate relationships, and reproductive decision-making, particularly during the transition to adulthood. METHODS: This cross-sectional study included 152 adolescents and young adults with PKU and 183 age-matched healthy controls. A questionnaire-based approach was used to assess sociodemographic characteristics, sexual behavior, and reproductive attitudes. Additional analyses within the PKU group examined sex- and age-related differences and factors associated with awareness of maternal PKU syndrome. RESULTS: Individuals with PKU differed from controls primarily in psychosocial and reproductive domains rather than in sexual behavior itself. Participants with PKU were more likely to live with parents, less frequently sexually active, and less likely to have children, particularly men. Among sexually active individuals, no significant differences were observed between groups in age at sexual initiation, number of sexual partners, or condom use. Within the PKU cohort, women were more likely to be sexually active, to live independently, to have children, and to report that PKU influenced decisions related to sexual initiation and parenthood. Awareness of maternal PKU syndrome was uneven and strongly associated with female sex, older age, higher education, sexual activity, and parenthood, indicating substantial knowledge gaps among younger individuals and men. CONCLUSIONS: PKU appears to be associated with delayed psychosocial transitions and reduced parenthood rather than altered sexual behavior per se. Marked sex differences in reproductive attitudes and disease-related knowledge highlight an unequal distribution of reproductive responsibility. These findings underscore the need to integrate structured sexual and reproductive health education into lifelong care for individuals with PKU, particularly during adolescence and early adulthood.

BACKGROUND: Phenylketonuria (PKU) is a rare metabolic disorder requiring lifelong dietary management. While clinical stability hinges on strict treatment adherence, this adherence is largely sustained by unpaid family caregiving, particularly in pediatric contexts. Yet, the lived experience of caregivers remains conceptually underexamined and largely absent from PKU research. This integrative review synthesizes empirical findings on caregiver burden in pediatric PKU and maps a multilevel burden structure that traces its structural, relational, and psychological dimensions. METHODS: Using Whittemore and Knafl's integrative methodology, 31 empirical studies-20 quantitative, 7 qualitative, and 4 mixed-methods-published between 2010 and 2025 were included. Studies were included if they reported on caregivers of pediatric PKU patients; studies focusing on adult patients or without caregiver data were excluded. Thematic coding and axial analysis were applied to identify macro (structural), meso (relational), and micro (psychological) patterns. Methodological triangulation enhanced both analytical rigor and conceptual depth. Studies were identified via a structured PubMed search (updated April 2025) and manual reference screening. RESULTS: The review included 31 empirical studies encompassing over 3000 caregivers across 12 countries. At the macro level, key themes included policy fragmentation, the feminization of caregiving roles, and financial precarity. Meso-level patterns revealed persistent emotional asymmetry, compounded relational overload, and hierarchical caregiving dynamics within family systems. At the micro level, caregivers reported chronic emotional depletion, elements of moral injury, and progressive role engulfment. Collectively, these findings outline a relational ecology of care in which emotional and physical caregiving labor operates as a compensatory mechanism for structural and institutional neglect. CONCLUSION: Family caregivers in pediatric PKU are not peripheral supporters but central contributors to clinical stability. Yet their role remains structurally unsupported and emotionally overburdened. Their psychosocial burden has direct clinical consequences for both the caregivers' health and the children's treatment outcomes. Sustainable PKU care-and by extension, care for other rare and chronic pediatric conditions-requires systemic investment in caregiving infrastructure, not as an act of goodwill, but as a clinical imperative. Findings should be interpreted in light of contextual heterogeneity and limited representation from low-income settings. SYSTEMATIC REVIEW REGISTRATION: Not registered.

Background/Objectives: In phenylketonuria (PKU), high blood phenylalanine (Phe) levels during pregnancy negatively influence foetal organogenesis and growth, leading to maternal PKU syndrome. Pregnancies must be carefully planned in order to maintain blood Phe levels ≤ 360 µmol/L pre-conception and throughout pregnancy. Our aim was to study metabolic control in PKU pregnancies across Europe. Methods: Eleven centres managing PKU participated. Data on blood Phe levels (µmol/L), natural protein intake (g/day), protein substitute intake (g/day) and maternal weight (kg) during pregnancy were collected retrospectively from dietetic records between 2012 and 2018. Results: In total, 84 female patients with PKU, accounting for 102 pregnancies (mean age: 30.4 ± 4.8 years), participated. Of these, 7 had hyperphenylalaninemia (HPA), 26 had mild PKU, 55 had classical PKU and 14 were unclassified. Sapropterin was prescribed in two pregnancies. Only 27% (28/102) of pregnancies successfully achieved consistent blood Phe levels ≤ 360 µmol/L for at least 2 weeks pre-conception. During pregnancy, 88% of blood Phe levels were ≤360 µmol/L, with a mean Phe of 229 ± 65 µmol/L. The mean number of blood Phe samples was 60 (1.5 per week) per pregnancy. In pre-pregnancy, over a mean of 2.9 years, only 35% of blood Phe levels were ≤360 µmol/L and 61% were <600 µmol/L. Post-pregnancy, over a mean of 2.8 years, 43% of Phe levels were <600 µmol/L with mean Phe 462 ± 226 µmol/L and 724 ± 230 µmol/L, respectively. 25% (25/102) had no levels performed post-pregnancy (mean of 2.8 ± 1.6 years) compared to 7% (7/102) pre-pregnancy (mean of 2.9 ± 1.5 years). Mean prescribed Phe intake pre-/during/post-pregnancy was 810 ± 721 vs. 787 ± 552 vs. 1110 ± 722 mg/day. Natural protein intake was 17 ± 15 vs. 17 ± 11 vs. 23 ± 15 g/day. Protein equivalent from protein substitute intake was 57 ± 21 vs. 66 ± 16 vs. 50 ± 23 g/day and total protein remained stable, 73 ± 14 vs. 83 ± 14 vs. 71 ± 19 g/day (1.1 ± 0.3 vs. 1.1 ± 0.4 vs. 1.0 ± 0.4 g/kg/day). Conclusions: Although a high level of metabolic control was maintained during pregnancy, fewer than 30% of pregnancies achieved constant Phe levels ≤ 360 µmol/L prior to conception, with minimal monitoring post-pregnancy. The long-term impact on the offspring remains unknown and requires further investigation.