Understanding Phenylketonuria: Causes, Symptoms, and Treatment

Phenylketonuria (PKU) is a rare genetic disorder that affects the way the body processes an amino acid called phenylalanine. It is an autosomal recessive disorder, meaning that it is inherited when both parents carry a mutated gene. PKU is classified as a classic or variant form, depending on the level of enzyme activity.

PKU can cause a variety of problems, including intellectual disability, developmental delays, and behavioral issues. If left untreated, the buildup of phenylalanine can lead to brain damage and other serious health problems.

Women with PKU who become pregnant have an increased risk of complications. If not properly managed, high levels of phenylalanine during pregnancy can result in birth defects and developmental delays in the baby.

Diagnosis of PKU is typically done through newborn screening, which involves testing a small blood sample from a newborn baby. If PKU is suspected, additional genetic testing may be done to confirm the diagnosis.

Treatment for PKU involves a strict low-phenylalanine diet, which restricts the intake of certain foods and requires the use of a special formula. Regular monitoring of blood phenylalanine levels is also necessary to ensure that the diet is effective in preventing high levels of phenylalanine.

Research on PKU and related conditions is ongoing. Studies are being conducted to better understand the genetic causes of PKU and the associated problems, as well as to develop new treatments and resources for people with PKU.

Major health insurance companies have faced legal trouble over their claim denial practices. In February 2018, the insurance commissioner of California announced plans to investigate Aetna’s coverage denial practices after a former medical director of the insurance company admitted that he never once looked at a patient’s medical records when deciding whether to deny claims over the three years he worked in the position, according to CNN.

For more information about PKU and resources for support and advocacy, you can visit OMIM, a catalog of human genes and genetic disorders, or search for articles and studies about PKU on PubMed. ClinicalTrials.gov is also a valuable resource for finding information about ongoing clinical trials for new treatments for PKU.

References:

Gizewska M, Huijbregts SCA, Gavage M, Lichter-Konecki U. Phenylketonuria: A Review of Current and Emerging Treatments. Ther Clin Risk Manag. 2020;16:1049-1064.
Lichter-Konecki U. Phenylketonuria: an update. Curr Opin Pediatr. 2020;32(6):769-776.

Frequency

Phenylketonuria (PKU) is a rare genetic condition that affects the way the body processes phenylalanine, an amino acid found in many foods. It is estimated that PKU affects approximately 1 in every 10,000 to 15,000 people worldwide.

PKU is inherited in an autosomal recessive manner, meaning that an individual must inherit two altered copies of the gene associated with PKU, one from each parent, in order to develop the condition. The gene responsible for PKU is called the PAH gene, which provides instructions for making the enzyme phenylalanine hydroxylase. Mutations in the PAH gene lead to reduced or absent activity of this enzyme, resulting in the accumulation of phenylalanine in the body.

PKU is more common in certain populations, such as individuals of European or Native American descent. It affects both males and females equally. Genetic testing can be performed to identify individuals who carry the altered gene associated with PKU or to confirm a diagnosis in individuals with symptoms suggestive of the condition.

According to clinicaltrialsgov, there are currently no studies listed evaluating the frequency of PKU in specific populations.

While PKU is a lifelong condition, it can be managed through a special diet that restricts the intake of phenylalanine. This dietary approach has been shown to prevent or minimize the development of intellectual disability and other neurological problems associated with PKU.

Support and resources for individuals with PKU and their families can be found through advocacy organizations, such as the National PKU Alliance and the Genetic and Rare Diseases Information Center. These organizations provide information about PKU, support for individuals and families, and resources for finding additional articles, studies, and clinical trials related to the condition.

Additional information about PKU can be found at OMIM, PubMed, and other scientific and medical resources.

Causes

Phenylketonuria (PKU) is a rare genetic health condition caused by a mutation in the gene responsible for producing the enzyme phenylalanine hydroxylase (PAH). PAH plays a crucial role in breaking down an amino acid called phenylalanine. When PAH is altered or absent, phenylalanine builds up to toxic levels in the blood and brain, leading to a range of problems and disabilities.

PKU is inherited in an autosomal recessive manner, meaning a child must inherit two copies of the mutated gene, one from each parent, to develop the condition. If both parents carry a single copy of the mutated gene, there is a 25% chance with each pregnancy to have a child with PKU.

The gene associated with PKU is called the PAH gene. Mutations in this gene can result in varying degrees of enzyme activity, leading to different forms of the condition. Classic PKU is the most severe form, characterized by little or no enzyme activity. Hyperphenylalaninemia refers to milder forms of the condition with some residual enzyme activity.

To diagnose PKU, genetic testing is performed to identify mutations in the PAH gene. This can be done through blood or saliva samples. Genetic counseling is also recommended for families affected by PKU to understand the inheritance pattern and make informed decisions about family planning.

Additional causes of high phenylalanine levels, known as hyperphenylalaninemia, can be due to mutations in other genes involved in the metabolism of phenylalanine. These conditions are often milder than classic PKU but still require management to prevent health problems.

Research studies and clinical trials are ongoing to understand the genetic basis of PKU, develop new treatment options, and improve the quality of life for patients. Organizations such as the PKU News, National PKU Alliance, and Advocacy for Patients with Inherited Metabolic Disorders are dedicated to providing support, information, and resources for people affected by PKU and their families.

For more information on PKU and related genetic conditions, resources such as PubMed, OMIM (Online Mendelian Inheritance in Man), and the Genetic and Rare Diseases Information Center can provide scientific articles, clinical information, and references for further reading.

Learn more about the gene associated with Phenylketonuria

Phenylketonuria (PKU) is a rare genetic disorder that affects the body’s ability to break down the amino acid phenylalanine. This condition is caused by mutations in the gene responsible for producing an enzyme called phenylalanine hydroxylase (PAH).

PAH is located on chromosome 12, and it plays a crucial role in the metabolism of phenylalanine. Mutations in the PAH gene can result in a partial or complete loss of enzyme activity, leading to the accumulation of phenylalanine in the body.

The PAH gene is inherited in an autosomal recessive manner, which means that both copies of the gene must be altered for a person to develop PKU. Individuals with only one altered copy of the gene are carriers and do not typically experience symptoms of the condition.

Inheritance

Phenylketonuria is an inherited condition caused by alterations in the gene that codes for the enzyme phenylalanine hydroxylase (PAH). This gene is located on chromosome 12q24.1.

The inheritance of phenylketonuria is autosomal recessive, which means that an affected person should inherit one altered copy of the gene from each parent. If only one copy of the gene is altered, the person will be a carrier but will not develop the condition.

The altered gene in phenylketonuria leads to a deficiency in the enzyme PAH, which is responsible for breaking down the amino acid phenylalanine. Without this enzyme, phenylalanine builds up in the blood and can cause serious health problems, including intellectual disability and brain damage.

Phenylketonuria has a frequency of approximately 1 in 10,000 to 15,000 births worldwide. The classic form of the condition, which results in severe intellectual disability, is less common and occurs in about 1 in 50,000 to 100,000 newborns.

The GeneReviews website provides more information about the inheritance and genetics of phenylketonuria. Additional scientific information can be found in the OMIM catalog of human genes and genetic disorders. ClinicalTrials.gov also provides references to ongoing research studies, including genetic testing and treatment trials for phenylketonuria.

Support and advocacy organizations such as the National PKU Alliance and the Phenylketonuria Research and Support Center offer resources and support for patients and their families. These organizations can provide information about genetic testing, treatment options, and additional research articles.

Other related genes associated with hyperphenylalaninemia and phenylketonuria include GCH1, PTS, and PAH. Studies on these genes and the protein they code for have provided valuable insights into the development and treatment of phenylketonuria.

Other Names for This Condition

Phenylketonuria
PKU
Hyperphenylalaninemia
Phenylalanine hydroxylase deficiency
PAH deficiency
Familial phenylketonuria
Hereditary phenylketonuria

Phenylketonuria, also known as PKU or hyperphenylalaninemia, is a rare genetic condition caused by a defect in the gene that codes for the enzyme phenylalanine hydroxylase (PAH). PAH is responsible for breaking down the amino acid phenylalanine. In individuals with PKU, the PAH enzyme is altered or absent, leading to a buildup of phenylalanine in the blood and tissues, which can cause brain damage and other health problems.

PKU is inherited in an autosomal recessive manner, meaning that individuals must inherit two altered copies of the PAH gene, one from each parent, in order to develop the condition. It is estimated that approximately 1 in every 10,000 to 15,000 newborns in the United States is born with PKU.

There are several other names and terms used to describe this condition, including classic PKU, non-PKU hyperphenylalaninemia, atypical PKU, and mild PKU. These terms refer to variations in the severity and presentation of the condition.

PKU can be diagnosed through newborn screening, which involves testing a blood sample taken from a baby’s heel shortly after birth. Early diagnosis is important, as treatment can begin immediately to prevent or minimize the development of symptoms and complications.

Treatment for PKU involves strict adherence to a phenylalanine-restricted diet. This diet involves avoiding high-protein foods and consuming special medical formulas and foods that are low in phenylalanine. Regular monitoring of blood phenylalanine levels and dietary adjustments are necessary to maintain appropriate levels of phenylalanine in the body.

In addition to dietary management, other treatment options for PKU include supplementation with specific nutrients, such as the amino acid tyrosine, which is often deficient in individuals with PKU, and the cofactor tetrahydrobiopterin (BH4), which can help activate the PAH enzyme in some cases.

Research on PKU and related conditions is ongoing. ClinicalTrials.gov is a good resource to learn more about current studies and clinical trials related to PKU. The Online Mendelian Inheritance in Man (OMIM) and PubMed databases can provide more information about the genetic and clinical aspects of PKU. Patient advocacy organizations, such as the National PKU Alliance, can also provide support and resources for individuals and families affected by PKU.

References:

Blau N, Erlandsen H. Phenylketonuria and BH4 deficiencies. 2019 Oct 3. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1504/.
Huijbregts SC, de Sonneville LM, Licht R, van Spronsen FJ, Verkerk PH, Sergeant JA. Sustained attention and inhibition of cognitive interference in treated phenylketonuria: associations with concurrent and lifetime phenylalanine concentrations. 2002 Aug;41(8):839-47. doi: 10.1111/1469-7610.00202. PMID: 12236627.
Gizewska M, Helwich E, Surdyk-Zasada J, Kazanowska-Zając K, Staszewska-Kalinska A, Ratajczyk J, Borkowska-Woś M, Sykut-Cegielska J. Early treatment improves intellectual outcome in patients with mild phenylketonuria. 2019;11:844. Published 2019 Oct 10. doi:10.3390/nu1110844

Additional Information Resources

Phenylketonuria (PKU) is a rare genetic condition that affects the metabolism of the amino acid phenylalanine. If left untreated, it can lead to severe intellectual disability and other health problems.

Here are some additional resources to learn more about PKU:

PKU Clinic: The PKU Clinic at the University of Colorado provides comprehensive care for people with PKU. They offer testing, treatment, and support for individuals with PKU and their families. Visit their website for more information.
National PKU Alliance: The National PKU Alliance is a non-profit organization that provides advocacy and support for individuals and families affected by PKU. They offer resources such as patient stories, educational materials, and a directory of PKU clinics. Learn more on their website.
Genetic and Rare Diseases Information Center: The Genetic and Rare Diseases Information Center (GARD) is a program of the National Center for Advancing Translational Sciences (NCATS). They provide reliable information about rare genetic diseases, including PKU. Visit their website to learn more.
OMIM: The Online Mendelian Inheritance in Man (OMIM) is a comprehensive catalog of human genes and genetic disorders. It provides information about the genes associated with PKU and the different forms of the condition. Visit their website for more details.
ClinicalTrials.gov: ClinicalTrials.gov is a database of clinical studies conducted around the world. You can search for ongoing studies related to PKU and hyperphenylalaninemia on their website. This can be a valuable resource for individuals looking to participate in research studies.
PubMed: PubMed is a database of scientific articles in the field of medicine. You can find research studies, case reports, and other publications related to PKU on their website. It is a great resource for staying up-to-date with the latest research.

Genetic Testing Information

Patient with phenylketonuria (PKU) experience a deficiency in the enzyme phenylalanine hydroxylase (PAH), which causes the accumulation of phenylalanine in the body. PKU is a rare genetic condition that is inherited in an autosomal recessive manner, meaning that an individual must inherit two altered copies of the PAH gene, one from each parent, to develop the condition.

Genetic testing can help diagnose PKU and identify individuals who carry altered copies of the PAH gene. It can also provide valuable information about the severity of the condition and guide treatment decisions.

There are several different genetic tests available for PKU. These tests can detect alterations in the PAH gene, as well as other genes that may be associated with the condition. Genetic testing can be done prenatally, in newborns, or in individuals who have symptoms suggestive of PKU.

One of the most common genetic tests for PKU is DNA sequencing, which involves analyzing the patient’s DNA to identify specific alterations in the PAH gene. This test can provide a definitive diagnosis and may also identify additional genetic variants that could contribute to the severity of the condition.

Genetic testing for PKU can also be used for carrier screening in individuals who are planning to have children. This can help identify individuals who carry altered copies of the PAH gene and may have an increased risk of having a child with PKU.

Genetic testing can provide valuable information about the inheritance pattern of PKU and help determine the risk of having a child with the condition. It can also provide important information about the specific genetic alterations associated with the condition, which can be helpful for understanding the underlying mechanisms and developing targeted treatments.

For more information about genetic testing for PKU, including available tests and support resources, patients and healthcare providers can refer to the following references:

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is an important resource for individuals seeking information on genetic and rare diseases. It provides information on the causes, symptoms, diagnosis, treatment, and prevention of these diseases.

GARD offers a wide range of detailed resources, including articles, references, and links to other websites and organizations. It also provides information on clinical trials, advocacy groups, research studies, and support services for patients and their families.

Phenylketonuria (PKU) is one of the rare genetic conditions covered by GARD. PKU is caused by alterations in the gene responsible for the production of the protein that metabolizes the amino acid phenylalanine. This alteration leads to a buildup of phenylalanine in the body, which can cause damage to the central nervous system and other health problems if left untreated.

The inheritance pattern of PKU is autosomal recessive, meaning that individuals need to inherit two altered copies of the gene, one from each parent, in order to develop the condition. People with PKU can pass on the altered gene to their children, who may also develop the condition if they inherit two altered copies.

GARD provides information on the frequency of PKU, which is estimated to affect about 1 in 10,000 to 15,000 newborns in the United States. It also offers resources on genetic testing for PKU and other rare diseases, as well as information on disability and support services for individuals living with PKU.

GARD offers references for further reading on PKU, including scientific articles, clinical trials, and patient resources. These references can be found in the GARD Catalog of Published Studies, OMIM (Online Mendelian Inheritance in Man), PubMed, and ClinicalTrials.gov.

References
Gizewska M, Huijbregts SC, Lichter-Konecki U. Phenylketonuria.
OMIM: 261600
Lichter-Konecki U, Huijbregts SC, Gizewska M. Phenylketonuria.
PubMed: 20301493
Gizewska M, Huijbregts SC, Lichter-Konecki U. Phenylketonuria.
ClinicalTrials.gov: phenylketonuria

By using GARD and its extensive resources, individuals can learn more about PKU and other rare genetic diseases. They can also find support and assistance in managing their condition and improving their overall health and well-being.

Patient Support and Advocacy Resources

Patients with Phenylketonuria (PKU) should have access to proper support and resources to manage their condition effectively. Here are some patient support and advocacy resources:

Gene Reviews: A comprehensive resource providing clinical information, genetic testing information, and references related to PKU. This resource is available at https://www.ncbi.nlm.nih.gov/books/NBK1504/.
OMIM: Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. It provides detailed information about PKU and its associated genes. More information can be found at https://omim.org/phenotypicSeries/PS261600.
Rare Diseases Clinical Research Network: This network provides information about PKU and research studies related to the condition. You can find more information at https://www.rarediseasesnetwork.org/cms/pku.
Rare Diseases Information Center: A comprehensive resource that offers information and support for patients and their families affected by rare diseases. You can visit their website at https://rarediseases.info.nih.gov/diseases/5867/pku.
Phenylketonuria Association: A patient advocacy organization providing support, resources, and education for individuals and families affected by PKU. Learn more about their work at https://www.pkunews.org/.

By accessing these resources, patients can learn more about Phenylketonuria, its causes, inheritance patterns, and the impact it has on health. They can also find information about available treatments, ongoing clinical trials, and support groups that can help them manage the condition effectively.

Research Studies from ClinicalTrials.gov

Phenylketonuria (PKU) is a rare genetic condition that affects the way the body breaks down a protein called phenylalanine. It is caused by mutations in the gene that produces an enzyme called phenylalanine hydroxylase. Without this enzyme, phenylalanine cannot be properly processed, leading to a buildup of toxic levels in the blood.

Research studies from ClinicalTrials.gov have provided more information about the causes, frequency, and associated health problems of phenylketonuria. Scientists have cataloged additional genes that can cause a similar condition called hyperphenylalaninemia, which is less severe than classic PKU. These studies have also investigated the inheritance patterns and genetic testing options for this condition.

Catalog of Genes and Diseases from OMIM

OMIM (Online Mendelian Inheritance in Man) is a comprehensive database that provides information about genes and genetic diseases. It is a valuable resource for advocacy, support, and research related to various genetic disorders, including Phenylketonuria (PKU) and other forms of hyperphenylalaninemia.

PKU is a rare genetic condition that affects the ability to break down the amino acid phenylalanine. This condition can cause a range of problems if left untreated, including intellectual disability and other neurological issues. Early testing and diagnosis are crucial, as the implementation of a special diet low in phenylalanine can prevent these problems from developing.

In the OMIM database, you can find information about the genes associated with PKU, such as the PAH gene, which encodes the enzyme phenylalanine hydroxylase. Variations or mutations in this gene can lead to the development of PKU.

To learn more about PKU and related conditions, you can explore scientific articles and references provided in the OMIM catalog. Additional information can be found in resources like PubMed and clinicaltrialsgov. These platforms offer access to studies, clinical trials, and other scientific research on PKU and the genes involved.

The OMIM catalog provides information about the inheritance patterns and frequency of PKU and other related diseases. PKU is inherited in an autosomal recessive manner, which means that both copies of the PAH gene need to be altered for the condition to manifest. The catalog also lists other genes associated with PKU, such as the GCH1 and PTS genes.

Understanding the genetic basis of PKU is crucial for developing effective treatments and supporting affected individuals. OMIM offers a wealth of information on different aspects of the condition, including genetic inheritance, molecular pathways, and potential treatment approaches.

List of Genes Associated with Phenylketonuria
Gene	OMIM Gene ID
PAH	612349
GCH1	600225
PTS	612719

By accessing the OMIM catalog, individuals, healthcare professionals, and researchers can find valuable resources, references, and support for understanding and managing Phenylketonuria and related disorders. It serves as a central hub for up-to-date information on the genetic causes, clinical manifestations, and treatments for a variety of rare genetic diseases.

Scientific Articles on PubMed

Phenylketonuria (PKU) is a rare genetic disorder that affects the body’s ability to break down the amino acid phenylalanine, which is found in protein. People with PKU have a defective gene that prevents the production of an enzyme needed to convert phenylalanine into another amino acid called tyrosine. This leads to an accumulation of phenylalanine in the body, which can cause severe health problems if left untreated.

PKU is inherited in an autosomal recessive manner, meaning that both parents must pass on a copy of the altered gene for a person to develop the condition. The frequency of PKU varies among different populations, with the highest rates seen in individuals of northern European and Turkish descent. PKU is often diagnosed through newborn screening, which involves testing a small blood sample from a baby’s heel a few days after birth.

Research on PKU and related disorders has led to a better understanding of the underlying genetic causes and has opened up new avenues for treatment. By studying the genes involved in PKU, scientists have been able to develop targeted therapies that aim to restore normal phenylalanine metabolism. Clinicaltrials.gov is a valuable resource for finding information about ongoing clinical trials investigating potential treatments for PKU and related conditions.

There are also many scientific articles available on PubMed that provide additional information on PKU and its associated health problems. These articles cover a wide range of topics, including the genetics of PKU, the clinical presentation and diagnosis of the condition, and the long-term effects of untreated PKU. Some articles focus on specific aspects of PKU, such as the impact of the condition on cognitive function or the effectiveness of different treatment strategies.

For individuals and families affected by PKU, advocacy organizations such as the National PKU Alliance and the European PKU Group provide support and resources. These organizations are dedicated to raising awareness about PKU, providing education and support to individuals living with the condition, and funding research to improve treatment options. In addition, the Online Mendelian Inheritance in Man (OMIM) database and the Catalog of Human Genes and Genetic Disorders are valuable sources of information on the genetic basis of PKU and related disorders.

In summary, PKU is a rare genetic disorder caused by mutations in the gene that encodes for the enzyme responsible for breaking down phenylalanine. Left untreated, PKU can cause severe intellectual disability and other health problems. Scientific articles on PubMed provide a wealth of information about the genetic causes, clinical presentation, and long-term effects of PKU. Advocacy organizations and online databases such as OMIM and the Catalog of Human Genes and Genetic Disorders can also provide additional resources and support for individuals and families affected by PKU.

References

Gizewska M, Huijbregts SCJ, Lichter-Konecki U. Phenylketonuria. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1504/
Kuvibidila SR. Phenylketonuria. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526007/
Huijbregts SCJ, de Sonneville LMJ, Licht R. Behavioral and cognitive findings in children with phenylketonuria. J Dev Behav Pediatr. 2002 Jun;23(3):227-41. doi: 10.1097/00004703-200206000-00013
Phenylketonuria. OMIM – Online Mendelian Inheritance in Man. Available from: https://www.omim.org/phenotypicSeries/PS261600
Phenylketonuria – Genetics Home Reference – NIH. U.S. National Library of Medicine. Available from: https://ghr.nlm.nih.gov/condition/phenylketonuria
Phenylketonuria (PKU). National Organization for Rare Disorders (NORD). Available from: https://rarediseases.org/rare-diseases/phenylketonuria/
Phenylketonuria. Genetics Home Reference. U.S. National Library of Medicine. Available from: https://ghr.nlm.nih.gov/condition/phenylketonuria#resources
Phenylketonuria. U.S. National Library of Medicine. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31643761

Frequency

Causes

Learn more about the gene associated with Phenylketonuria

Inheritance

Other Names for This Condition

Additional Information Resources

Genetic Testing Information

Genetic and Rare Diseases Information Center

Patient Support and Advocacy Resources

Research Studies from ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

FANCG gene

Chromosome 9

MMACHC gene

Frequency

Causes

Learn more about the gene associated with Phenylketonuria

Inheritance

Other Names for This Condition

Additional Information Resources

Genetic Testing Information

Genetic and Rare Diseases Information Center

Patient Support and Advocacy Resources

Research Studies from ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

Related Posts