Disorder of phenylalanine metabolism

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ORPHA:284814
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4Active trials23Specialists8Treatment centers

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UniteRare data is sourced from FDA.gov, ClinicalTrials.gov, Orphanet, OMIM, and NORD.
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Overview

Disorder of phenylalanine metabolism is a group of conditions where the body has trouble processing an amino acid called phenylalanine (often shortened to 'Phe'). Amino acids are the building blocks of protein, and phenylalanine is found in many foods we eat. Normally, the body converts phenylalanine into another amino acid called tyrosine using a specific enzyme. When this process does not work properly, phenylalanine can build up in the blood and brain, potentially causing harm to the nervous system. The most well-known condition in this group is phenylketonuria (PKU), but this broader category also includes milder forms sometimes called hyperphenylalaninaemia (HPA) and conditions caused by problems making or recycling the cofactor (called BH4 or tetrahydrobiopterin) that the enzyme needs to work. Symptoms can range from very mild (no noticeable problems) to severe, including intellectual disability, seizures, behavioral issues, and a musty body odor if left untreated. The good news is that newborn screening programs in many countries can detect elevated phenylalanine levels within the first few days of life. Early diagnosis and treatment — usually through a strict low-protein diet and sometimes medication — can prevent most of the serious complications. Treatment options have expanded in recent years, including the FDA-approved medication sapropterin (Kuvan) for BH4-responsive forms and pegvaliase (Palynziq) for adults with PKU. Ongoing management throughout life is important to maintain good health and brain function.

Key symptoms:

Intellectual disability if untreatedSeizuresMusty or mousy body odorLight skin, hair, and eyes compared to family membersEczema or skin rashesBehavioral problems such as hyperactivityAnxiety and depressionDifficulty concentratingTremors or movement problems (especially in BH4 deficiency)Delayed development in untreated infantsIrritabilityMicrocephaly (small head size) if untreatedPoor growth in severe untreated cases

Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Neonatal

Begins at or shortly after birth (first 4 weeks)

Orphanet ↗NORD ↗

FDA & Trial Timeline

9 events
Mar 2026Multiomics Approach in Adult Patients With Phenylketonuria

University Hospital, Tours

TrialNOT YET RECRUITING
Jan 2026The Psychosocial Functioning of Adults With Phenylketonuria.

Central Hospital, Nancy, France

TrialNOT YET RECRUITING
Jan 2026Assessment of Gut Microbiota-Derived Amino Acid Metabolite Production in Patients With MASLD

Hospices Civils de Lyon — NA

TrialNOT YET RECRUITING
Dec 2025To Evaluate the Safety and Efficacy of GS1168 Injection in Adult Phenylketonuria

Gritgen Therapeutics Co., Ltd. — EARLY_PHASE1

TrialNOT YET RECRUITING
Dec 2025Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers

University of Missouri-Columbia — NA

TrialRECRUITING
Jul 2025A Phase 2 Study of JNT-517 in Adolescent Participants With Phenylketonuria

Otsuka Pharmaceutical Development & Commercialization, Inc. — PHASE2

TrialRECRUITING
Jun 2025A Study to Evaluate the Long-Term Safety and Efficacy of JNT-517 in Participants With Phenylketonuria

Otsuka Pharmaceutical Development & Commercialization, Inc. — PHASE3

TrialNOT YET RECRUITING
Nov 2022A Global, Multicenter Study to Assess Maternal, Fetal and Infant Outcomes of Exposure to Palynziq® (Pegvaliase) During Pregnancy and Breastfeeding

BioMarin Pharmaceutical — NA

TrialRECRUITING
Sep 2020AAV Gene Therapy Study for Subjects with PKU

BioMarin Pharmaceutical — PHASE1, PHASE2

TrialACTIVE NOT RECRUITING

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Treatments

No FDA-approved treatments are currently listed for Disorder of phenylalanine metabolism.

4 clinical trialsare actively recruiting — trials can provide access to cutting-edge therapies.

View clinical trials →

Clinical Trials

4 recruitingView all trials with filters →
Phase 21 trial
A Phase 2 Study of JNT-517 in Adolescent Participants With Phenylketonuria
Phase 2
Actively Recruiting
· Sites: Dallas, Texas · Age: 1217 yrs
N/A2 trials
Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers
N/A
Actively Recruiting
PI: Shawn Christ · Sites: Columbia, Missouri · Age: 1860 yrs
A Global, Multicenter Study to Assess Maternal, Fetal and Infant Outcomes of Exposure to Palynziq® (Pegvaliase) During Pregnancy and Breastfeeding
N/A
Actively Recruiting
PI: Medical Director, MD (BioMarin Pharmaceutical) · Sites: Wilmington, North Carolina; Calgary +2 more

Specialists

23 foundView all specialists →
LM
Louis J Elsas, MD
Specialist
PI on 1 active trial1 Disorder of phenylalanine metabolism publication
HM
Hans C Andersson, MD
NEW ORLEANS, LA
Specialist
PI on 1 active trial
SP
Shoji Yano, MD, Ph.D.
LOS ANGELES, CA
Specialist
PI on 1 active trial
JM
Joshua Lilienstein, M.D.
JAMAICA PLAIN, MA
Specialist
PI on 1 active trial
RP
Rajavel Elango, PhD
Vancouver, British Columbia
Specialist

Rare Disease Specialist

PI on 5 active trials
AM
Annette Feigenbaum, MD
SAN DIEGO, CA
Specialist
PI on 1 active trial1 Disorder of phenylalanine metabolism publication
KM
Komudi Siriwardena, MD
Specialist
PI on 1 active trial
MM
Minjoo Kim, MS
PALMETTO, FL
Specialist
PI on 1 active trial
RM
Raed Selmi, MD-PhD
Specialist
PI on 1 active trial
AP
Anita MacDonald, BSc PhD
Specialist
PI on 1 active trial
RR
Rani H Singh, PhD, RD
DECATUR, GA
Specialist
PI on 1 active trial1 Disorder of phenylalanine metabolism publication
RM
Richard Koch, M.D.
Specialist
PI on 1 active trial
JM
John M Miles, MD
Specialist
PI on 1 active trial
DR
Denise M Ney, PhD, RD
Specialist
PI on 1 active trial
SP
Sandra Van Calcar, PhD
Specialist
PI on 1 active trial
AP
Anita MacDonald, Pr.
Specialist
PI on 1 active trial
ŞD
Şenay ÇETİNKAYA, Doç. Dr.
Specialist
PI on 1 active trial
JP
Joyanna Hansen, PhD
PORTLAND, OR
Specialist
PI on 1 active trial
RL
Rani H Singh, PhD, RD, LD
DECATUR, GA
Specialist
PI on 1 active trial
BM
Bobbye M. Rouse, M.D.
Specialist
PI on 1 active trial
RM
Reuben Matalon, M.D.
Specialist
PI on 1 active trial

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to Disorder of phenylalanine metabolism.

Search all travel grants →NORD Financial Assistance ↗

Community

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Latest news about Disorder of phenylalanine metabolism

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Caregiver Resources

NORD Caregiver Resources

Support, advocacy, and financial assistance for caregivers of rare disease patients.

Mental Health Support

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Family & Caregiver Grants

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Social Security Disability

Learn how rare disease patients may qualify for SSDI/SSI benefits.

Questions for your doctor

Bring these to your next appointment

  • Q1.What specific type of phenylalanine metabolism disorder does my child have, and what gene variants were found?,What is the target phenylalanine blood level we should aim for, and how often should we test?,Is my child a candidate for sapropterin (Kuvan) or other medications?,How do I work with a metabolic dietitian to plan safe and nutritious meals?,What are the long-term risks if phenylalanine levels are not well controlled?,Are there any clinical trials or new treatments we should know about?,What special considerations are needed for pregnancy planning in the future?

Common questions about Disorder of phenylalanine metabolism

What is Disorder of phenylalanine metabolism?

Disorder of phenylalanine metabolism is a group of conditions where the body has trouble processing an amino acid called phenylalanine (often shortened to 'Phe'). Amino acids are the building blocks of protein, and phenylalanine is found in many foods we eat. Normally, the body converts phenylalanine into another amino acid called tyrosine using a specific enzyme. When this process does not work properly, phenylalanine can build up in the blood and brain, potentially causing harm to the nervous system. The most well-known condition in this group is phenylketonuria (PKU), but this broader cate

How is Disorder of phenylalanine metabolism inherited?

Disorder of phenylalanine metabolism follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Disorder of phenylalanine metabolism typically begin?

Typical onset of Disorder of phenylalanine metabolism is neonatal. Age of onset can vary across affected individuals.

Are there clinical trials for Disorder of phenylalanine metabolism?

Yes — 4 recruiting clinical trials are currently listed for Disorder of phenylalanine metabolism on UniteRare. See the clinical trials section on this page for phase, sponsor, and site details sourced from ClinicalTrials.gov.

Which specialists treat Disorder of phenylalanine metabolism?

23 specialists and care centers treating Disorder of phenylalanine metabolism are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.