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Orphanet: Phenylketonuria
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class="row g-0"> <div class="col-12"> <div class="result-detail"> <div class="d-flex justify-content-between mb-4 mx-4"> <h2>Phenylketonuria</h2> <div class="btn text-white bg-orpa-blue" role="button" id="suggest-modal-btn" data-orphacode="716"> <span id="spinner" class="spinner-border-sm" role="status" aria-hidden="true"></span> <i class="fas fa-pen me-1"></i>Suggest an update </div> </div> <div class="alert d-none mx-4"> <span class="success d-none"> Your message has been sent </span> <span class="error d-none"> Your message has not been sent. Please contact an administrator. </span> </div> <div class="modal fade" id="suggest-modal" tabindex="-1" aria-labelledby="#suggest-modal" aria-hidden="true"> <div class="modal-dialog modal-xl"> <div class="modal-content rounded-0"> <div class="modal-header rounded-0 py-0 justify-content-between text-white px-2 bg-orpa-blue"> Comment Form <div type="button" class="p-1" data-bs-dismiss="modal" aria-label="Close">X</div> </div> <div class="modal-body" data-orphacode="716"> </div> </div> </div> </div> <div class="mx-4 mb-4 p-4 service-color-box"> <strong class="d-block mb-3 service-color">Disease definition</strong> <p> A rare inborn error of amino acid metabolism characterized by elevated blood phenylalanine and low levels or absence of phenylalanine hydroxylase enzyme. If not detected early or left untreated, the disorder manifests with mild to severe mental disability. </p> </div> <div class="mx-4 mb-4 p-4 bg-gray"> <p class="fs-5 d-block mb-2 fw-bold">ORPHA:716</p> <p> <a href=" /en/disease/classification/list/name/Phenylketonuria?orphaCode=716">Classification level: Disorder</a> </p> <div class="row"> <div class="col-6"> <strong>Synonym(s): </strong> <ul class="list-unstyled"> <li class="m-2">PAH deficiency</li> <li class="m-2">PKU</li> <li class="m-2">Phenylalanine hydroxylase deficiency</li> </ul> </div> <div class="col-3"> <p class="mt-3"> <strong>Prevalence: </strong> <span>1-9 / 100 000</span> </p> <p><strong>Inheritance: </strong><span>Autosomal recessive</span></p> <p><strong>Age of onset: </strong><span>Infancy</span></p> </div> <div class="col-3"> <p> <strong>ICD-10: </strong> E70.0 , E70.1 </p> <p><strong>ICD-11: </strong> <a target="_blank" href="https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/444122923">5C50.0</a> </p> <p><strong>OMIM: </strong> <a target="_blank" href="//omim.org/entry/261600">261600</a> </p> <p><strong>UMLS: </strong> C0031485 </p> <p><strong>MeSH: </strong> D010661 </p> <p><strong>GARD: </strong> <a target="_blank" href="//rarediseases.info.nih.gov/diseases/7383/index">7383</a> </p> <p><strong>MedDRA: </strong> <span> 10034872 </span> </p> </div> </div> </div> <div class="h2 ms-4 mb-4">Summary</div> <div class="mx-4 summary"> <div class="fs-5 orpha-blue">Epidemiology</div> <p class="mx-4">The prevalence of phenylketonuria (PKU) shows considerable geographic variation. It is estimated to be 1/10,000 live births in Europe with a higher rate in some countries (Ireland, Italy). Prevalence is particularly high in Turkey: 1/4,000 live births. PKU is far rarer in the Finnish, African and Japanese populations.</p> <div class="fs-5 orpha-blue">Clinical description</div> <p class="mx-4">In the absence of neonatal diagnosis, symptoms develop within a few months of birth, may be very mild to severe and include gradual developmental delay, stunted growth, microcephaly, seizures, tremors, eczema, vomiting, and musty odor. Untreated patients subsequently develop intellectual disability, behavioral disorders (hyperactivity) and motor disorders. Patients often have fair coloring as a result of tyrosine deficiency. The most common form of the condition is known as classical phenylketonuria and is characterized by severe symptoms. A mild form has also been described (mild PKU), and an even milder form known as mild hyperphenylalaninemia (mild HPA or non-PKU HPA). A subset of patients with milder phenotypes has been found to be responsive to tetrahydrobiopterin (BH4), the cofactor of phenylalanine hydroxylase (BH4-responsive HPA).</p> <div class="fs-5 orpha-blue">Etiology</div> <p class="mx-4">PKU is caused by a wide range of variants in the <i>PAH</i> gene (12q22-q24.2) coding for phenylalanine hydroxylase. Non-<i>PAH</i> variants have been reported to cause a disorder known as hyperphenylalaninemia due to BH4 deficiency. Variant frequency varies among different ethnic groups. Lower levels or absence of the phenylalanine hydroxylase enzyme underlie the clinical manifestations, as a result of toxic accumulation of phenylalanine in the blood and brain.</p> <div class="fs-5 orpha-blue">Diagnostic methods</div> <p class="mx-4">The disorder is usually diagnosed through neonatal screening programs.</p> <div class="fs-5 orpha-blue">Differential diagnosis</div> <p class="mx-4">PKU should be distinguished from BH4 deficiency.</p> <div class="fs-5 orpha-blue">Genetic counseling</div> <p class="mx-4">Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child at each pregnancy.</p> <div class="fs-5 orpha-blue">Management and treatment</div> <p class="mx-4">The mainstay of treatment is a low-phenylalanine diet and amino acids mixture for the forms that require treatment. According to the European guidelines for the management of PKU, the recommended maintenance level is usually between 120 and 360 micromol/L in newborns, with treatment considered essential in older patients with levels above 600 micromol/L.</p> <div class="fs-5 orpha-blue">Prognosis</div> <p class="mx-4">Prognosis is variable, but favorable if diagnosed early and treated properly.</p> <span class="expert-list fst-italic fw-lighter"> Last update: <span class="fw-bold">December 2020</span> </span> <span class="expert-list fst-italic fw-lighter"> - Expert reviewer(s): <span class="fw-bold">Pr Nenad BLAU </span> </span> </div> <div class="mx-4 mb-3 mt-4 fw-bold"> <i class="fas fa-book orpha-blue fs-4"></i> A summary on this disease is available in <span> <a href="/fr/disease/detail/716">Fran莽ais</a> (2020) </span> <span> <a href="/es/disease/detail/716">Espa帽ol</a> (2020) </span> <span> <a href="/de/disease/detail/716">Deutsch</a> (2020) </span> <span> <a href="/it/disease/detail/716">Italiano</a> (2020) </span> <span> <a href="/pt/disease/detail/716">Portugu锚s</a> (2012) </span> <span> <a href="/nl/disease/detail/716">Nederlands</a> (2020) </span> <span> <a href="/pl/disease/detail/716">Polski</a> (2025) </span> <span> <a href="https://www.orpha.net/data/patho/FI/FenyyliketonuriaPKU-FifiAbs611-p-ivitys-2014.pdf">Suomi</a> (2012.pdf) </span> <span> <a href="http://www.orpha.net/data/patho/Pro/pl/Fenyloketonuria_PL_pl_PRO_ORPHA716.pdf">Polski</a> (2012.pdf) </span> <span> <a href="https://www.orpha.net/data/patho/GR/--GRgrAbs611.pdf">螘位位畏谓喂魏维</a> (2012.pdf) </span> <span> <a href="https://www.orpha.net/data/patho/SK/Phenylketonuria.pdf">Sloven膷ina</a> (2012.pdf) </span> </div> <div class="m-4 bg-gray p-4"> <div class="h4" id="detailed-info"><i class="fas fa-file"></i> Detailed information</div> <div class="row mt-2 small"> <div class="col-md-6 col-12"> <h5 class="fw-bold mt-4">General public</h5> <div class="mt-3"> <strong class="mb-2"> <i class="fas fa-angle-right fs-6 orpha-blue"></i> Article for general public </strong> <div class="mt-1"> <a target="_blank" href="http://www.orpha.net/data/patho/Pub/fr/Phenylcetonurie-FRfrPub611v01.pdf">Fran莽ais (2012.pdf)</a> <span class="fst-italic small"> - Orphanet</span> <br /> </div> <div class="mt-1"> <a target="_blank" href="https://www.socialstyrelsen.se/kunskapsstod-och-regler/omraden/sallsynta-halsotillstand/om-kunskapsdatabasen/sok-bland-sallsynta-halsotillstand/fenylketonuri/">Svenska (2020)</a> <span class="fst-italic small"> - Socialstyrelsen</span> <br /> </div> </div> <h5 class="fw-bold mt-4">Guidelines</h5> <div class="mt-3"> <strong class="mb-2"> <i class="fas fa-angle-right fs-6 orpha-blue"></i> Emergency guidelines </strong> <div class="mt-1"> <a target="_blank" href="https://www.orpha.net/data/patho/Emg/fr/Urgences_Phenylcetonurie-frPro611.pdf">Fran莽ais (2014.pdf)</a> <span class="fst-italic small"> - Orphanet Urgences</span> <br /> </div> <div class="mt-1"> <a target="_blank" href="https://www.filiere-g2m.fr/media/attachments/2023/08/16/en_gb_cu_pcu-13.07.23-v2.pdf">English (2023.pdf)</a> <span class="fst-italic small"> - G2M</span> <img src="/build/images/FSMR.png" alt="Logo FSMR"> <br /> </div> <div class="mt-1"> <a target="_blank" href="http://www.orpha.net/data/patho/Emg/Int/es/Fenilcetonuria_ES_es_EMG_ORPHA716.pdf">Espa帽ol (2019.pdf)</a> <span class="fst-italic small"> - Orphanet Urgences</span> <br /> </div> </div> <div class="mt-3"> <strong class="mb-2"> <i class="fas fa-angle-right fs-6 orpha-blue"></i> Clinical practice guidelines </strong> <div class="mt-1"> <a target="_blank" href="http://www.has-sante.fr/portail/jcms/c_953467/fr/phenylcetonurie">Fran莽ais (2018)</a> <span class="fst-italic small"> - PNDS</span> <img src="/build/images/FSMR.png" alt="Logo FSMR"> <br /> </div> <div class="mt-1"> <a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/34784942/">English (2021)</a> <span class="fst-italic small"> - Orphanet J Rare Dis</span> <img src="/build/images/ERN.png" alt="Logo ERN"> <br /> </div> <div class="mt-1"> <a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/29025426/">English (2017)</a> <span class="fst-italic small"> - Orphanet J Rare Dis</span> <br /> </div> </div> </div> <div class="col-md-6 col-12"> <h5 class="fw-bold mt-4">Disease review articles</h5> <div class="mt-3"> <strong class="mb-2"> <i class="fas fa-angle-right fs-6 orpha-blue"></i> Clinical genetics review </strong> <div class="mt-1"> <a target="_blank" href="http://www.ncbi.nlm.nih.gov/books/n/gene/pku/">English (2017)</a> <span class="fst-italic small"> - GeneReviews</span> <br /> </div> </div> <h5 class="fw-bold mt-4">Patient-Centered Outcome Measures (PCOMs)</h5> <div class="mt-3"> <strong class="mb-2"> <i class="fas fa-angle-right fs-6 orpha-blue"></i> Patient-Centered Outcome Measures (PCOMs) </strong> <div class="mt-1"> <a target="_blank" href="https://eprovide.mapi-trust.org/advanced-search?database=proqolid&therapeuticIndications%5B%5D=Phenylketonurias">English (2023)</a> <span class="fst-italic small"> - PROQOLID<sup>TM</sup></span> <br /> </div> </div> <h5 class="fw-bold mt-4">Genetic testing</h5> <div class="mt-3"> <strong class="mb-2"> <i class="fas fa-angle-right fs-6 orpha-blue"></i> Guidance for genetic testing </strong> <div class="mt-1"> <a target="_blank" href="https://www.nature.com/articles/ejhg2011172">English (2011)</a> <span class="fst-italic small"> - Eur J Hum Genet</span> <br /> </div> </div> </div> </div> <p class="small mt-4"> <img src="/build/images/ERN.png" alt="Logo ERN">: produced/endorsed by ERN(s) <img src="/build/images/FSMR.png" alt="Logo FSMR">: produced/endorsed by FSMR(s) </p> </div> <div class="m-4 service-color-box p-4"> <div class="h4 mb-4"><i class="fas fa-file"></i> Additional information</div> <div class="row"> <div class="col-4"> <p class="fw-bold">Further information on this disease</p> <ul class="list-unstyled"> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/disease/classification/list/name/Phenylketonuria?orphaCode=716"> Classification(s) (3)</a> </li> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/disease/gene/list/716?mode=name"> Gene(s) (1)</a> </li> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/disease/sign/716"> Clinical Signs and Symptoms</a> </li> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=phenylketonuria%5Bmajr%5D"> Publications in PubMed</a> </li> </ul> </div> <div class="col-4"> <p class="fw-bold">Patient-centred resources for this disease</p> <ul class="list-unstyled"> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/expert-centres/centres/716?name=Phenylketonuria&consulting=medical&age=all&official=0"> Expert centre(s) (323) </a> </li> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/expert-centres/networks?orphaCode=716&diseaseName=Phenylketonuria"> Networks of expert centre (14) </a> </li> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/diagnostic-tests/diagnostics?orphaCode=716&diseaseName=Phenylketonuria"> Diagnostic tests (142) </a> </li> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/patient-organisations?orphaCode=716&diseaseName=Phenylketonuria"> Patient organisation(s) (144) </a> </li> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/patient-organisations/federations-alliances?orphaCode=716&diseaseName=Phenylketonuria"> Federation/alliance(s) (44) </a> </li> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/drug?orphaCode=716&diseaseName=Phenylketonuria&status=all&mode=pat"> Orphan designation(s) and orphan drug(s) (25) </a> </li> </ul> </div> <div class="col-4"> <p class="fw-bold">Research activities on this disease</p> <ul class="list-unstyled"> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/research-trials/research-projects?orphaCode=716&diseaseName=Phenylketonuria"> Research project(s) (87) </a> </li> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/research-trials/clinical-trials?orphaCode=716&diseaseName=Phenylketonuria"> Clinical trial(s) (5) </a> </li> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/research-trials/biobanks?orphaCode=716&diseaseName=Phenylketonuria"> Biobank(s) (10) </a> </li> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/research-trials/registries?orphaCode=716&diseaseName=Phenylketonuria"> Registry(ies) (29) </a> </li> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a href="/en/institutions/expert-networks?orphaCode=716&diseaseName=Phenylketonuria"> Network of experts (10) </a> </li> </ul> <p class="fw-bold">Newborn screening</p> <ul class="list-unstyled"> <li class="my-1"> <i class="fas fa-angle-right orpha-blue"></i> <a target="_blank" href="https://nbs.orphanet.app/?lang=en">Newborn screening library</a> </li> </ul> </div> </div> </div> <div class="mx-4"> <small>The documents contained in this website are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.</small> </div> </div> </div> </div> </div> </main> </div> </article> </article> </main> <script src="/build/runtime.f3575a88.js" defer></script><script src="/build/755.5a8586e9.js" defer></script><script src="/build/673.f47275b8.js" defer></script><script src="/build/467.7cd7293e.js" defer></script><script src="/build/app.3c0fe482.js" defer></script> <script type="application/json" data-placeholders> {"gene":"Gene name or symbol","name":"Disease name","orpha":"ORPHAcode","mim":"OMIM disease","mimg":"OMIM gene","omim":"OMIM disease","icd10":"ICD-10","icd11":"ICD-11"} </script> <script type="application/ld+json"> { "@context": "http://schema.org/", "@type": "MedicalCondition", "@id": "https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=716", "identifier": "716", "name": { "@type": "PronounceableText", "inLanguage": "EN", "textValue": "Phenylketonuria" }, "alternateName": [ "PAH deficiency", "PKU", "Phenylalanine hydroxylase deficiency" ], "epidemiology": "Prevalence : 1-5 / 10 000", "code": [ { "@type": "MedicalCode", "codeValue": "ORPHA:716", "codingSystem": "ORPHAcode" }, { "@type": "MedicalCode", "codeValue": "10034872", "codingSystem": "MedDRA" }, { "@type": "MedicalCode", "codeValue": "https://pubmed.ncbi.nlm.nih.gov/?term=phenylketonuria%5Bmajr%5D", "codingSystem": "Medline" }, { "@type": "MedicalCode", "codeValue": "E70.0", "codingSystem": "ICD-10" }, { "@type": "MedicalCode", "codeValue": "261600", "codingSystem": "OMIM" }, { "@type": "MedicalCode", "codeValue": "190687004", "codingSystem": "SNOMED CT" }, { "@type": "MedicalCode", "codeValue": "E70.1", "codingSystem": "ICD-10" }, { "@type": "MedicalCode", "codeValue": "D010661", "codingSystem": "MeSH" }, { "@type": "MedicalCode", "codeValue": "C0031485", "codingSystem": "UMLS" }, { "@type": "MedicalCode", "codeValue": "5C50.0", "codingSystem": "ICD-11" }, { "@type": "MedicalCode", "codeValue": "7383", "codingSystem": "GARD" } ], "description": "A rare inborn error of amino acid metabolism characterized by elevated blood phenylalanine and low levels or absence of phenylalanine hydroxylase enzyme. 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