Home / Deep Research / Phenylketonuria

Phenylketonuria

1. Disease Information

2026-04-25
Falcon MONDO:0009861 Model: Edison Scientific Literature 33 citations

1. Disease Information

1.1 What is the disease?

PKU is defined in authoritative guideline and review literature as an autosomal recessive defect of phenylalanine metabolism due to phenylalanine hydroxylase (PAH) deficiency, causing elevated Phe in blood/brain and (if untreated) severe neurodevelopmental sequelae. (spronsen2017keyeuropeanguidelines pages 1-1, martinez2024state‐of‐the‐art2023on pages 1-3)

Direct abstract quote (European guideline): “Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency in the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine.” (spronsen2017keyeuropeanguidelines pages 1-1)

1.2 Key identifiers (requested: OMIM, Orphanet, ICD-10/ICD-11, MeSH, MONDO)

1.3 Synonyms and alternative names

Frequently used equivalents include: * PAH deficiency / phenylalanine hydroxylase deficiency (common in guidelines and mechanistic reviews). (spronsen2017keyeuropeanguidelines pages 1-1, martinez2024state‐of‐the‐art2023on pages 1-3) * Hyperphenylalaninemia (HPA) is often used as an umbrella phenotype category; PKU is typically reserved for higher untreated Phe ranges or clinically significant disease requiring treatment. (pinto2024bloodphenylalaninelevels pages 2-3, hofman2018dietaryadherencein pages 41-45)

1.4 Evidence sources: individual vs aggregated resources

Most core disease knowledge (definition, targets, thresholds) is derived from aggregated guideline and consensus processes (systematic evidence grading plus Delphi methods) as in the European guidelines. (spronsen2017keyeuropeanguidelines pages 1-1)

2. Etiology

2.1 Disease causal factors

Primary cause (genetic/mechanistic): biallelic PAH variants → reduced PAH enzyme activity → increased Phe and altered Tyr availability; PAH uses tetrahydrobiopterin (BH4) as a cofactor. (pinto2024bloodphenylalaninelevels pages 2-3, spronsen2017keyeuropeanguidelines pages 1-1)

2.2 Risk factors

  • Genetic: pathogenic PAH variants (many alleles; an example allele specifically noted in a recent European cohort paper is c.1222C>T (p.Arg408Trp)). (pinto2024bloodphenylalaninelevels pages 2-3)
  • Environmental / behavioral: the dominant modifiable “risk factor” for clinical deterioration is chronic exposure to elevated blood Phe, largely driven by difficulty adhering to restrictive diet over time. Age-related deterioration of metabolic control is documented in large European real-world data. (pinto2024bloodphenylalaninelevels pages 2-3)

2.3 Protective factors

2.4 Gene–environment interaction

PKU is a canonical gene–environment interaction disease: the genotype (residual PAH function; BH4 responsiveness) interacts with dietary Phe exposure to determine blood Phe and outcomes; guideline targets are operationalized as blood Phe thresholds for lifelong management. (spronsen2017keyeuropeanguidelines pages 1-1, spronsen2017keyeuropeanguidelines pages 4-5)

3. Phenotypes (clinical spectrum)

3.1 Phenotype spectrum and laboratory phenotype categories

A commonly used severity schema (based on untreated Phe) includes: * Mild hyperphenylalaninemia: ~120–600 µmol/L * Classic PKU: often >1200 µmol/L These categorical thresholds are summarized in recent literature and reviews. (alfadhel2024firstsuccessfuloutcomes pages 1-2, yu2025advancinggenetherapy pages 2-4)

3.2 Major clinical manifestations (with suggested HPO terms)

Untreated/late-treated PKU is associated with severe neurodevelopmental outcomes (intellectual disability, seizures/epilepsy, behavioral problems). (spronsen2017keyeuropeanguidelines pages 1-1)

Early-treated PKU (lifelong care): subtle but clinically relevant outcomes can persist, especially with higher Phe exposure: * Executive dysfunction (HP:0000726) * Attention deficit (HP:0007018) * Memory impairment (HP:0002354) * Anxiety (HP:0000739) * Depressive mood (HP:0000716) * Ataxia (HP:0001251) / tremor (HP:0001337) These associations are emphasized in cohort and guideline discussions linking blood Phe to neuropsychological and neurological outcomes. (pinto2024bloodphenylalaninelevels pages 2-3, spronsen2017keyeuropeanguidelines pages 4-5)

3.3 Age of onset, progression, and frequency

3.4 Quality of life (QoL) impact (recent primary data)

In a cross-sectional European study of 124 adults with early-treated classical PKU, most QoL domains showed “little or no impact,” and “more than three-quarters” rated their health status as good/very good/excellent; however, fatigue (“tiredness”), guilt about dietary non-adherence, and pregnancy-related Phe concerns were salient. (maissenabgottspon2023healthrelatedqualityof pages 1-2)

4. Genetic / Molecular Information

4.1 Causal genes

4.2 Pathogenic variants (current understanding)

A comprehensive variant catalogue is not present in the retrieved texts, but recent gene-therapy-oriented reviews note very large allelic heterogeneity (thousands of reported PAH variants) and population-specific common alleles; example common alleles are listed (e.g., R408W). (yu2025advancinggenetherapy pages 2-4)

4.3 BH4 responsiveness (therapeutic stratifier)

BH4 responsiveness is central to precision management: * European guidelines note that “some patients benefit from tetrahydrobiopterin (BH4).” (spronsen2017keyeuropeanguidelines pages 1-1) * Expert consensus highlights substantial non-responsiveness in more severe phenotypes; one expert consensus summary states “about 50–80% of patients, especially those with a more severe disease phenotype, are unresponsive to sapropterin.” (rocha2023expertconsensuson pages 1-2)

4.4 Modifier genes / epigenetics / chromosomal abnormalities

Not extractable from the currently retrieved texts.

5. Environmental Information

The dominant environmental determinant of phenotype severity is dietary phenylalanine exposure (and adherence to medical nutrition therapy), rather than exogenous toxins or infections. Restrictive dietary therapy itself can influence broader physiology (e.g., nutrient status), motivating ongoing monitoring and therapy optimization. (rocha2023expertconsensuson pages 1-2, pinto2024bloodphenylalaninelevels pages 2-3)

6. Mechanism / Pathophysiology

6.1 Causal chain (upstream → downstream)

  1. PAH deficiency reduces hepatic conversion of Phe → Tyr (BH4-dependent). (spronsen2017keyeuropeanguidelines pages 1-1, pinto2024bloodphenylalaninelevels pages 2-3)
  2. Elevated blood Phe and altered amino-acid balance leads to brain exposure.
  3. Neurotoxicity mechanisms include reduced transport of other large neutral amino acids across the blood–brain barrier and downstream neurotransmitter synthesis disruption.

Guidelines explicitly note that high Phe causes neurocognitive impairment via “reduced LNAA transport and decreases in neurotransmitter synthesis (↓Trp→↓serotonin; ↓Tyr→↓dopamine).” (spronsen2017keyeuropeanguidelines pages 4-5)

6.2 Neuroimaging/brain structure outcomes (recent studies)

Adult treated PKU still shows structural brain differences in contemporary cohorts: * In a neurodevelopmental disorders study (PKU n=35; controls n=22), adults with PKU had lower Full Scale IQ and reduced volumes in pallidum, hippocampus, amygdala, brainstem, and total cerebral white matter; blood Phe correlated negatively with pallidum and brainstem volumes. (pinto2024bloodphenylalaninelevels pages 2-3)

6.3 Suggested ontology terms

  • GO biological processes: phenylalanine catabolic process; aromatic amino acid family metabolic process; neurotransmitter biosynthetic process.
  • UBERON anatomical sites: liver (primary metabolic defect), brain/white matter/subcortical structures (major affected targets).
  • CHEBI: phenylalanine; tyrosine; tetrahydrobiopterin.

(These ontology mappings are consistent with the mechanistic chain described in guidelines and cohort papers, though explicit ontology annotations are not contained in the retrieved texts.) (pinto2024bloodphenylalaninelevels pages 2-3, spronsen2017keyeuropeanguidelines pages 4-5)

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

9.1 Inheritance

Autosomal recessive inheritance is consistently stated in guidelines and contemporary reviews. (spronsen2017keyeuropeanguidelines pages 1-1, martinez2024state‐of‐the‐art2023on pages 1-3)

9.2 Epidemiology / prevalence / incidence

Not extractable from the currently retrieved texts.

9.3 Real-world metabolic-control statistics (Europe 2012–2018)

A 9-centre European/Turkish retrospective study of 1323 patients (age 1–57 years) reported that the percentage of Phe values within target declined with increasing age, with a particularly low proportion in older adults (≥41 years: 40%). (pinto2024bloodphenylalaninelevels pages 2-3)

10. Diagnostics

10.1 Screening

Newborn screening is the standard population screening approach for early identification and prevention of severe sequelae. (spronsen2017keyeuropeanguidelines pages 1-1)

10.2 Key diagnostic biomarker and targets

Blood phenylalanine (Phe) is the core biomarker for diagnosis and management. (spronsen2017keyeuropeanguidelines pages 1-1, pinto2024bloodphenylalaninelevels pages 2-3)

European 2017 guideline targets and treatment thresholds: * Targets: 120–360 µmol/L (0–12 years and maternal PKU) and 120–600 µmol/L (>12 years, non-pregnant). (spronsen2017keyeuropeanguidelines pages 1-1, spronsen2017keyeuropeanguidelines pages 4-5) * Threshold logic: no intervention if untreated Phe <360 µmol/L; treat to age 12 when untreated Phe is 360–600 µmol/L; lifelong treatment if untreated Phe >600 µmol/L. (spronsen2017keyeuropeanguidelines pages 1-1)

11. Outcome / Prognosis

11.1 Prognostic factors

Blood Phe exposure is repeatedly emphasized as the key modifiable prognostic factor; higher Phe is associated with worse neurocognitive and some structural brain outcomes. (pinto2024bloodphenylalaninelevels pages 2-3, spronsen2017keyeuropeanguidelines pages 4-5)

11.2 Maternal PKU (teratogenic risk)

European guidelines specify tighter pregnancy targets (120–360 µmol/L) and note that women with untreated Phe <360 µmol/L may not require lowering for pregnancy, reflecting the established fetal risk from elevated maternal Phe. (spronsen2017keyeuropeanguidelines pages 4-5)

12. Treatment (current practice, 2023–2024 developments)

12.1 Medical nutrition therapy (MNT)

MNT (low-Phe diet + protein substitutes/medical foods) remains foundational. Expert consensus in adults (Delphi panel) concluded MNT has limited long-term effectiveness, is associated with high treatment burden, and many adults cannot achieve adequate metabolic control on diet alone—supporting an “unmet need” in adult PKU. (rocha2023expertconsensuson pages 1-2)

Expert opinion signal: The same consensus notes an 85% agreement statement that adults should be offered pharmacologic options when available. (rocha2023expertconsensuson pages 4-5)

12.2 Sapropterin (BH4 analogue)

Sapropterin (BH4) is used for responsive patients with residual PAH activity. In the European cohort (n=1323), sapropterin-treated patients (n=222) had statistically lower mean Phe and higher proportion within target than diet-only, though the mean difference was modest. (pinto2024bloodphenylalaninelevels pages 2-3)

12.3 Pegvaliase (enzyme substitution therapy)

A 2023 update of the web-based GMDI/SERN PKU nutrition management guideline incorporated pegvaliase implementation and monitoring, noting regulatory approvals (FDA 2018; EMA 2019) and the possibility of substantial diet liberalization with successful therapy. (cunningham2023nutritionmanagementof pages 1-2)

Quantitative efficacy and safety (PAL-003 extension): In a long-term phase 2 extension (n=68 entering extension), mean Phe decreased ~59% to ~542 µmol/L at Week 48; thresholds ≤120, ≤360, and ≤600 µmol/L were achieved by ~79–83% of participants. Injection-site reactions, erythema, headache, and arthralgia were common; most AEs were mild/moderate. (longo2018longtermsafetyand pages 1-2)

12.4 Emerging therapies (2024–2026 clinical development)

JNT-517 (oral small-molecule; Otsuka) — clinical trials

  • NCT06971731 (Phase 3 adults; n≈120): randomized placebo-controlled trial with primary endpoint percent change in plasma Phe at Weeks 2/4/6 for 150 mg BID; includes responder thresholds such as <600, <360, <120 µmol/L. (NCT06971731 chunk 1)
  • NCT06637514 (Phase 2 adolescents 12–<18; n≈10): primary objectives safety/tolerability/PK; secondary outcomes include changes in plasma and urinary Phe. (NCT06637514 chunk 1)
  • NCT05781399 (First-in-human, healthy + PKU adults): includes urinary amino-acid change measures and PK comparisons. (NCT05781399 chunk 2)
  • NCT06628128 (Phase 3 open-label extension): long-term safety (TEAEs) and metabolic outcomes (plasma/urinary Phe; dietary intake). (NCT06628128 chunk 1)

AAV gene therapy (liver-directed PAH gene addition) — clinical trials

  • BMN 307 (BioMarin) — NCT04480567 (Phase 1/2; open-label; dose escalation; n≈100): primary outcome is change from baseline in mean plasma Phe at Week 12; secondary outcomes include Phe and dietary protein intake at Week 96 and TEAEs up to 5 years. (NCT04480567 chunk 1)
  • Reviews of gene therapy note ongoing/terminated AAV programs and highlight safety concerns (e.g., transaminase elevations) and challenges for long-term expression, particularly in younger patients. (martinez2024state‐of‐the‐art2023on pages 10-12, yu2025advancinggenetherapy pages 11-12)

12.5 Suggested MAXO terms (examples)

  • Dietary phenylalanine restriction / medical nutrition therapy (MAXO: dietary therapy)
  • Sapropterin pharmacotherapy (MAXO: pharmacotherapy)
  • Pegvaliase enzyme therapy (MAXO: enzyme replacement/enzyme substitution therapy)
  • AAV-based gene transfer (MAXO: gene therapy)

(Explicit MAXO identifiers were not present in retrieved texts; these are conceptual mappings.)

13. Prevention

14. Other species / natural disease

Not addressed in the retrieved evidence.

15. Model organisms

A 2024 gene-therapy review notes that murine models replicate key aspects of human pathology and are extensively used for liver-directed gene therapy proof-of-principle, including multiple vector/editing approaches; a classic model referenced is the homozygous enu2/2 mouse. (martinez2024state‐of‐the‐art2023on pages 10-12)

Recent developments (prioritizing 2023–2024)

  1. Guideline/practice update for pegvaliase nutrition management (Jun 2023) with implementation toolkits for initiation, monitoring, and special populations. URL: https://doi.org/10.1186/s13023-023-02751-0 (cunningham2023nutritionmanagementof pages 1-2)
  2. Delphi expert consensus (Sep 2023) highlighting limitations/burden of lifelong diet therapy in adults and recommending pharmacologic options when available. URL: https://doi.org/10.3390/nu15183940 (rocha2023expertconsensuson pages 4-5)
  3. Large multi-centre real-world European dataset (Jun 2024) quantifying age-associated deterioration in metabolic control and association of monitoring frequency with control. URL: https://doi.org/10.3390/nu16132064 (pinto2024bloodphenylalaninelevels pages 2-3)
  4. Gene therapy state-of-the-art (Aug 2024) summarizing AAV, lentiviral, and nonviral/LNP mRNA approaches and the translational barriers. URL: https://doi.org/10.1002/jimd.12651 (martinez2024state‐of‐the‐art2023on pages 1-3)

Data gaps vs requested template

Several template elements could not be completed from the currently retrieved texts, notably: MONDO/MeSH/Orphanet/ICD identifiers; prevalence/incidence and carrier frequencies; detailed PAH variant spectra with ClinVar/gnomAD frequencies; modifier genes/epigenetics; comprehensive organ-system comorbidity statistics from the 2024 somatic comorbidity SLR (full numeric extraction was not available in the retrieved snippets); and detailed cross-species natural disease information. Where these items are essential for a knowledge base entry, direct database retrieval (Orphanet/MONDO/MeSH/ICD; ClinVar; gnomAD; registry epidemiology sources) and full-text extraction of the SLR’s included primary studies would be required. (whitehall2024systematicliteraturereview pages 49-49)

References

  1. (pinto2024bloodphenylalaninelevels pages 2-3): Alex Pinto, Kirsten Ahring, Manuela Ferreira Almeida, Catherine Ashmore, Amaya Bélanger-Quintana, Alberto Burlina, Turgay Coşkun, Anne Daly, Esther van Dam, Ali Dursun, Sharon Evans, François Feillet, Maria Giżewska, Hulya Gökmen-Özel, Mary Hickson, Yteke Hoekstra, Fatma Ilgaz, Richard Jackson, Alicja Leśniak, Christian Loro, Katarzyna Malicka, Michał Patalan, Júlio César Rocha, Serap Sivri, Iris Rodenburg, Francjan van Spronsen, Kamilla Strączek, Ayşegül Tokatli, and Anita MacDonald. Blood phenylalanine levels in patients with phenylketonuria from europe between 2012 and 2018: is it a changing landscape? Nutrients, 16:2064, Jun 2024. URL: https://doi.org/10.3390/nu16132064, doi:10.3390/nu16132064. This article has 14 citations.

  2. (spronsen2017keyeuropeanguidelines pages 1-1): Francjan J van Spronsen, Annemiek MJ van Wegberg, Kirsten Ahring, Amaya Bélanger-Quintana, Nenad Blau, Annet M Bosch, Alberto Burlina, Jaime Campistol, Francois Feillet, Maria Giżewska, Stephan C Huijbregts, Shauna Kearney, Vincenzo Leuzzi, Francois Maillot, Ania C Muntau, Fritz K Trefz, Margreet van Rijn, John H Walter, and Anita MacDonald. Key european guidelines for the diagnosis and management of patients with phenylketonuria. The Lancet Diabetes & Endocrinology, 5:743-756, Sep 2017. URL: https://doi.org/10.1016/s2213-8587(16)30320-5, doi:10.1016/s2213-8587(16)30320-5. This article has 551 citations and is from a highest quality peer-reviewed journal.

  3. (martinez2024state‐of‐the‐art2023on pages 1-3): Michael Martinez, Cary O. Harding, Gerald Schwank, and Beat Thöny. State‐of‐the‐art 2023 on gene therapy for phenylketonuria. Journal of Inherited Metabolic Disease, 47:80-92, Aug 2024. URL: https://doi.org/10.1002/jimd.12651, doi:10.1002/jimd.12651. This article has 43 citations and is from a peer-reviewed journal.

  4. (cunningham2023nutritionmanagementof pages 1-2): Amy Cunningham, Fran Rohr, Patricia Splett, Shideh Mofidi, Heather Bausell, Adrya Stembridge, Aileen Kenneson, and Rani H. Singh. Nutrition management of pku with pegvaliase therapy: update of the web-based pku nutrition management guideline recommendations. Orphanet Journal of Rare Diseases, Jun 2023. URL: https://doi.org/10.1186/s13023-023-02751-0, doi:10.1186/s13023-023-02751-0. This article has 32 citations and is from a peer-reviewed journal.

  5. (maissenabgottspon2023healthrelatedqualityof pages 1-2): Stephanie Maissen-Abgottspon, Raphaela Muri, Michel Hochuli, Péter Reismann, András Gellért Barta, Ismail Mucahit Alptekin, Álvaro Hermida-Ameijeiras, Alessandro P. Burlina, Alberto B. Burlina, Chiara Cazzorla, Jessica Carretta, Roman Trepp, and Regula Everts. Health-related quality of life in a european sample of adults with early-treated classical pku. Orphanet Journal of Rare Diseases, Sep 2023. URL: https://doi.org/10.1186/s13023-023-02917-w, doi:10.1186/s13023-023-02917-w. This article has 14 citations and is from a peer-reviewed journal.

  6. (spronsen2017keyeuropeanguidelines pages 4-5): Francjan J van Spronsen, Annemiek MJ van Wegberg, Kirsten Ahring, Amaya Bélanger-Quintana, Nenad Blau, Annet M Bosch, Alberto Burlina, Jaime Campistol, Francois Feillet, Maria Giżewska, Stephan C Huijbregts, Shauna Kearney, Vincenzo Leuzzi, Francois Maillot, Ania C Muntau, Fritz K Trefz, Margreet van Rijn, John H Walter, and Anita MacDonald. Key european guidelines for the diagnosis and management of patients with phenylketonuria. The Lancet Diabetes & Endocrinology, 5:743-756, Sep 2017. URL: https://doi.org/10.1016/s2213-8587(16)30320-5, doi:10.1016/s2213-8587(16)30320-5. This article has 551 citations and is from a highest quality peer-reviewed journal.

  7. (rocha2023expertconsensuson pages 1-2): Júlio César Rocha, Kirsten K. Ahring, Heather Bausell, Deborah A. Bilder, Cary O. Harding, Anita Inwood, Nicola Longo, Ania C. Muntau, André L. Santos Pessoa, Fran Rohr, Serap Sivri, and Álvaro Hermida. Expert consensus on the long-term effectiveness of medical nutrition therapy and its impact on the outcomes of adults with phenylketonuria. Nutrients, 15:3940, Sep 2023. URL: https://doi.org/10.3390/nu15183940, doi:10.3390/nu15183940. This article has 15 citations.

  8. (rocha2023expertconsensuson pages 4-5): Júlio César Rocha, Kirsten K. Ahring, Heather Bausell, Deborah A. Bilder, Cary O. Harding, Anita Inwood, Nicola Longo, Ania C. Muntau, André L. Santos Pessoa, Fran Rohr, Serap Sivri, and Álvaro Hermida. Expert consensus on the long-term effectiveness of medical nutrition therapy and its impact on the outcomes of adults with phenylketonuria. Nutrients, 15:3940, Sep 2023. URL: https://doi.org/10.3390/nu15183940, doi:10.3390/nu15183940. This article has 15 citations.

  9. (martinez2024state‐of‐the‐art2023on pages 10-12): Michael Martinez, Cary O. Harding, Gerald Schwank, and Beat Thöny. State‐of‐the‐art 2023 on gene therapy for phenylketonuria. Journal of Inherited Metabolic Disease, 47:80-92, Aug 2024. URL: https://doi.org/10.1002/jimd.12651, doi:10.1002/jimd.12651. This article has 43 citations and is from a peer-reviewed journal.

  10. (hofman2018dietaryadherencein pages 41-45): DL Hofman. Dietary adherence in phenylketonuria (pku) and effects on cognitive function and quality of life. Unknown journal, 2018.

  11. (alfadhel2024firstsuccessfuloutcomes pages 1-2): Majid Alfadhel and Rayyan Albarakati. First successful outcomes of pegvaliase (palynziq) in children. BMC Medical Genomics, Mar 2024. URL: https://doi.org/10.1186/s12920-024-01847-1, doi:10.1186/s12920-024-01847-1. This article has 3 citations and is from a peer-reviewed journal.

  12. (yu2025advancinggenetherapy pages 2-4): In-sun Yu and Jaemin Jeong. Advancing gene therapy for phenylketonuria: from precision editing to clinical translation. International Journal of Molecular Sciences, 26:8722, Sep 2025. URL: https://doi.org/10.3390/ijms26178722, doi:10.3390/ijms26178722. This article has 3 citations.

  13. (longo2018longtermsafetyand pages 1-2): Nicola Longo, Roberto Zori, Melissa P. Wasserstein, Jerry Vockley, Barbara K. Burton, Celeste Decker, Mingjin Li, Kelly Lau, Joy Jiang, Kevin Larimore, and Janet A. Thomas. Long-term safety and efficacy of pegvaliase for the treatment of phenylketonuria in adults: combined phase 2 outcomes through pal-003 extension study. Orphanet Journal of Rare Diseases, Jul 2018. URL: https://doi.org/10.1186/s13023-018-0858-7, doi:10.1186/s13023-018-0858-7. This article has 37 citations and is from a peer-reviewed journal.

  14. (NCT06971731 chunk 1): A Study to Evaluate the Safety and Efficacy of JNT-517 in Participants With Phenylketonuria (PKU). Otsuka Pharmaceutical Development & Commercialization, Inc.. 2025. ClinicalTrials.gov Identifier: NCT06971731

  15. (NCT06637514 chunk 1): A Phase 2 Study of JNT-517 in Adolescent Participants With Phenylketonuria. Otsuka Pharmaceutical Development & Commercialization, Inc.. 2025. ClinicalTrials.gov Identifier: NCT06637514

  16. (NCT05781399 chunk 2): First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria. Otsuka Pharmaceutical Development & Commercialization, Inc.. 2022. ClinicalTrials.gov Identifier: NCT05781399

  17. (NCT06628128 chunk 1): A Study to Evaluate the Long-Term Safety and Efficacy of JNT-517 in Participants With Phenylketonuria. Otsuka Pharmaceutical Development & Commercialization, Inc.. 2025. ClinicalTrials.gov Identifier: NCT06628128

  18. (NCT04480567 chunk 1): AAV Gene Therapy Study for Subjects with PKU. BioMarin Pharmaceutical. 2020. ClinicalTrials.gov Identifier: NCT04480567

  19. (yu2025advancinggenetherapy pages 11-12): In-sun Yu and Jaemin Jeong. Advancing gene therapy for phenylketonuria: from precision editing to clinical translation. International Journal of Molecular Sciences, 26:8722, Sep 2025. URL: https://doi.org/10.3390/ijms26178722, doi:10.3390/ijms26178722. This article has 3 citations.

  20. (whitehall2024systematicliteraturereview pages 49-49): Kaleigh B. Whitehall, Sarah Rose, Gillian E. Clague, Kirsten K. Ahring, Deborah A. Bilder, Cary O. Harding, Álvaro Hermida, Anita Inwood, Nicola Longo, François Maillot, Ania C. Muntau, André L. S. Pessoa, Júlio C. Rocha, Fran Rohr, Serap Sivri, Jack Said, Sheun Oshinbolu, and Gillian C. Sibbring. Systematic literature review of the somatic comorbidities experienced by adults with phenylketonuria. Orphanet Journal of Rare Diseases, Aug 2024. URL: https://doi.org/10.1186/s13023-024-03203-z, doi:10.1186/s13023-024-03203-z. This article has 12 citations and is from a peer-reviewed journal.