*  Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU - Full...
It is difficult for many patients to maintain reduced blood Phe, and many patients with PKU experience some degree of ... Phenylketonurias. Brain Diseases, Metabolic, Inborn. Brain Diseases, Metabolic. Brain Diseases. Central Nervous System Diseases ... MedlinePlus related topics: Phenylketonuria Drug Information available for: Phenylalanine Sapropterin Sapropterin ... Genetic and Rare Diseases Information Center resources: Phenylketonuria Inborn Amino Acid Metabolism Disorder ...
  https://clinicaltrials.gov/ct2/show/NCT00838435
*  Kuvan® in Phenylketonuria Patients Less Than 4 Years Old - Full Text View - ClinicalTrials.gov
Phenylketonurias. Brain Diseases, Metabolic, Inborn. Brain Diseases, Metabolic. Brain Diseases. Central Nervous System Diseases ... Kuvan® in Phenylketonuria Patients Less Than 4 Years Old (SPARK). This study has been completed. ... Phenylketonuria (PKU). Kuvan® (Sapropterin). Phe-restricted diet. Paediatric ,4 years old. responders to BH4. Phe tolerance. ... MedlinePlus related topics: Phenylketonuria Drug Information available for: Phenylalanine Sapropterin Sapropterin ...
  https://clinicaltrials.gov/ct2/show/NCT01376908
*  Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) Patients -...
Phenylketonurias. Brain Diseases, Metabolic, Inborn. Brain Diseases, Metabolic. Brain Diseases. Central Nervous System Diseases ... Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) Patients. ... Phenylketonuria (PKU) results from deficient phenylalanine hydroxylase (PAH) activity and leads to toxic phenylalanine (Phe) ... This study, PKU-016, will be conducted in PKU patients to evaluate the therapeutic effects of sapropterin dihydrochloride on ...
  https://clinicaltrials.gov/ct2/show/NCT01114737?cond=%22Phenylketonuria%22&rank=7
*  The Effects of Sapropterin Dihydrochloride Supplementation on in Vivo Redox Status in Patients With Classical PKU - Full Text...
Oxidative stress in patients with phenylketonuria. Biochim Biophys Acta. 2005 Apr 15;1740(1):68-73. Epub 2005 Feb 25. ... Phenylketonurias. Brain Diseases, Metabolic, Inborn. Brain Diseases, Metabolic. Brain Diseases. Central Nervous System Diseases ... Determine in vivo redox status in patients with classical phenylketonuria. The primary objective of this study is to determine ... The primary objective of this study is to determine oxidative stress in patients with classical phenylketonuria (PKU) enrolled ...
  https://clinicaltrials.gov/ct2/show/NCT01650909?recr=Open&cond=%22Phenylketonurias%22&rank=11
*  Nutritional and Neurotransmitter Changes in PKU Subjects on BH4 - Full Text View - ClinicalTrials.gov
Phenylketonuria) patient population, investigators do not know the full effects this medicine will have on the patient's diet, ... Phenylketonurias. Brain Diseases, Metabolic, Inborn. Brain Diseases, Metabolic. Brain Diseases. Central Nervous System Diseases ... Patients will be given 4 weeks to demonstrate a response to KuvanTM as determined by a drop in plasma PHE by ≥15%. All patients ... BACKGROUND : Tetrahydrobiopterin (BH4) is a treatment option newly available to phenylketonuria (PKU) patients within the ...
  https://clinicaltrials.gov/ct2/show/NCT00688844
*  Hyperphenylalaninemia - Wikipedia
Hyperphenylalaninemia is a medical condition characterized by mildly or strongly elevated concentrations of the amino acid phenylalanine in the blood. Phenylketonuria (PKU) can result in severe hyperphenylalaninemia. Phenylalanine concentrations ([phe]) are routinely screened in newborns by the neonatal heel prick (Guthrie test), which takes a few drops of blood from the heel of the infant. Standard [phe] concentrations in unaffected persons are about 60µM: [phe] concentrations in persons with untreated phenylketonuria may be many times that (600µM to 2400µM), which indicate that the child is at risk for severe intellectual disability. Phenylketonuria is classed as an autosomal recessive condition: in heterozygous form, [phe] shows a moderate elevation, perhaps two-fold over that of unaffected homozygotes, which is classified as hyperphenylalaninemia (hyper- + phenylalanine + -emia = high [phe] in blood). The coloration of the skin, hair, and eyes is ...
  https://en.wikipedia.org/wiki/Hyperphenylalaninemia
*  Genetical heterogeneity of phenylketonuria
Abstract: Data on genetic nature of phenylketonuria molecular mechanisms of its pathogenesis and approaches to treatment and prophylaxis of the disease are reviewed. Genetic heterogeneity of phenylketonuria, dependent on polylocus control of phenylalanine hydroxylase complex, is considered in detail. A possibility is discussed of the existence of the genetically different forms of phenylketonuria. Data on the molecular structure of phenylalanine hydroxylase and cooperative nature of its active site are discussed. Variations in pathogenesis of different forms of the phenylketonuria, theoretical and practical significance of these investigations are considered ...
  http://pbmc.ibmc.msk.ru/index.php/en/article/PBMC-1982-28-3-62-en
*  The 48-hour tetrahydrobiopterin loading test in patients with phenylketonuria: evaluation of protocol and influence of baseline...
BACKGROUND: The 24- and 48-hour tetrahydrobiopterin (BH4) loading test (BLT) performed at a minimum baseline phenylalanine concentration of 400 mumol/l is commonly used to test phenylketonuria patients for BH4 responsiveness. This study aimed to analyze differences between the 24- and 48-hour BLT and the necessity of the 400 mumol/l minimum baseline phenylalanine concentration. METHODS: Data on 186 phenylketonuria patients were collected. Patients were supplemented with phenylalanine if phenylalanine was <400 mumol/l. BH4 20mg/kg was administered at T = 0 and T = 24. Blood samples were taken at T=0, 8, 16, 24 and 48 h. Responsiveness was defined as >/= 30% reduction in phenylalanine concentration at >/= 1 time point. RESULTS: Eighty-six (46.2%) patients were responsive. Among responders 84% showed a >/= 30% response at T = 48. Fifty-three percent had their maximal decrease at T = 48. Fourteen ...
  http://repository.ubn.ru.nl/handle/2066/97409
*  Cognitive outcomes in early-treated adults with phenylketonuria (PKU) - Research Explorer : Aston University
OBJECTIVE: Phenylketonuria (PKU) is an inherited metabolic disease which affects cognitive functions due to an inability to metabolize phenylalanine which leads to the accumulation of toxic by-products (Phe) in the brain. PKU can be effectively treated with a low phenylalanine diet, but some cognitive deficits remain. Studies have reported impairments, especially for processing speed and executive functions, but there is a lack of comprehensive assessment across cognitive domains. Moreover, it is important to establish outcomes in early treated adults with PKU (AwPKU) who have better metabolic control than groups previously reported in the literature.. METHOD: We tested 37 AwPKU with an unprecedented number of tasks (N = 28) and measures (N = 44) and compared results with 30 controls matched for age and education.. RESULTS: We found (a) group impairments, particularly in tasks tapping speed of processing and complex executive functions; (b) high variability across participants, with a ...
  https://research.aston.ac.uk/portal/en/researchoutput/cognitive-outcomes-in-earlytreated-adults-with-phenylketonuria-pku
*  Response to Kuvan® in Subjects With Phenylketonuria (PKU) in a 4 Weeks Testing Period - Full Text View - ClinicalTrials.gov
The PKU is categorized as per phenotype into classical PKU: (blood Phe levels , 1200 mcmol/l), mild PKU (blood Phe levels 600 to 1200 mcmol/l), mild HPA (blood Phe levels 300 to 600 mcmol/l). Early responders defined as percentage of participants with at least 30 percent reduction in Phe levels within the first seven days of treatment. Late responders defined as percentage of participants with less than 30 percent reduction in Phe levels within first seven days of treatment, but at least 30 percent reduction in Phe levels within 28 +/- 1 days of treatment. Partial responders defined as percentage of participants with Phe levels reduction between 10 and 30 percent at any blood measurement within the 28 +/- 1 days of treatment ...
  https://clinicaltrials.gov/ct2/show/NCT01082328?cond=%22phenylketonuria%22&rank=12
*  Metabolites | Free Full-Text | New Strategies for the Treatment of Phenylketonuria (PKU)
Phenylketonuria (PKU) was the first inherited metabolic disease in which dietary treatment was found to prevent the disease's clinical features. Treatment of phenylketonuria remains difficult due to progressive decrease in adherence to diet and the presence of neurocognitive defects despite therapy. This review aims to summarize the current literature on new treatment strategies. Additions to treatment include new, more palatable foods based on glycomacropeptide that contains very limited amount of aromatic amino acids, the administration of large neutral amino acids to prevent phenylalanine entry into the brain or tetrahydropterina cofactor capable of increasing residual activity of phenylalanine hydroxylase. Moreover, human trials have recently been performed with subcutaneous administration of phenylalanine ammonia-lyase, and further efforts are underway to develop an oral therapy containing phenylanine ammonia-lyase. Gene therapy also seems to be a promising approach in ...
  http://www.mdpi.com/2218-1989/4/4/1007
*  Phenylketonuria - SNPedia
Phenylketonuria (PKU) was one of the first inherited metabolic diseases to be tested for in newborns. PKU is a rare enzyme deficiency; only about 250 babies are born with this condition in the United States each year. It is important to test for PKU because if it is not detected at birth, the enzyme deficiency will cause an entirely preventable form of mental retardation. An infant who inherits two copies of a mutation in the phenylalanine hydroxylase (PAH) gene cannot metabolize the amino acid phenylalanine found in proteins. With a normal diet, the phenylalanine level rises too high, and the baby develops brain damage and mental retardation. Children with PKU who are given a strict low-phenylalanine diet from infancy will not develop brain damage. Common foods that contain phenylalanine include milk and eggs. The artificial sweetener NutraSweet (aspartame) contains phenylalanine, so food and drinks that use this sweetener are also banned from the PKU diet. A woman with PKU who is or wants ...
  https://www.snpedia.com/index.php/Phenylketonuria
*  What Is Biochemistry - Phenylketonuria - Medicalrealm
Patient with phenylketonuria may present with phenylketone in the urine and musty urine odor. Besides that patient may also present with other symptoms and signs of phenylketonuria such as eczema, hypertonia, mental retardation, growth failure, heavy p
  http://www.medicalrealm.net/what-is-biochemistry---phenylketonuria.html
*  Urinary Excretion of Amines in Phenylketonuria and Mongolism | Science
Children with phenylketonuria excrete considerably less serotonin and tryptamine and somewhat less normetanephrine and p-tyramine than normal children. The excretion of these amines was not decreased in mongolism. Even during monoamine oxidase blockade, o-tyramine could not be detected in the urine of phenylketonurics. These findings are discussed in relation to the mental defect of phenylketonuria. ...
  http://science.sciencemag.org/content/136/3519/879
*  The Effects of Sapropterin Dihydrochloride Supplementation on in Vivo Redox Status in Patients With Classical PKU - Full Text...
This study is an independent sub-study of the protocol titled PKU-016: A double-blind, placebo-controlled, randomized study to evaluate the safety and therapeutic effects of sapropterin dihydrochloride on neuro-psychiatric symptoms in subjects with phenylketonuria (PKU ASCEND).. The primary objective of this study is to determine oxidative stress in patients with classical phenylketonuria (PKU) enrolled in PKU-016, using a brain scan (called an HMPAO SPECT) at baseline and 26 weeks, and blood redox biomarkers. ...
  https://clinicaltrials.gov/ct2/show/NCT01650909?recr=Open&cond=%22Brain+Diseases%2C+Metabolic%2C+Inborn%22&rank=18
*  The Effects of Sapropterin Dihydrochloride Supplementation on in Vivo Redox Status in Patients With Classical PKU - Full Text...
This study is an independent sub-study of the protocol titled PKU-016: A double-blind, placebo-controlled, randomized study to evaluate the safety and therapeutic effects of sapropterin dihydrochloride on neuro-psychiatric symptoms in subjects with phenylketonuria (PKU ASCEND).. The primary objective of this study is to determine oxidative stress in patients with classical phenylketonuria (PKU) enrolled in PKU-016, using a brain scan (called an HMPAO SPECT) at baseline and 26 weeks, and blood redox biomarkers. ...
  https://clinicaltrials.gov/ct2/show/NCT01650909?recr=Open&cond=%22Brain+Diseases%2C+Metabolic%2C+Inborn%22&rank=19
*  The Effects of Sapropterin Dihydrochloride Supplementation on in Vivo Redox Status in Patients With Classical PKU - Full Text...
This study is an independent sub-study of the protocol titled PKU-016: A double-blind, placebo-controlled, randomized study to evaluate the safety and therapeutic effects of sapropterin dihydrochloride on neuro-psychiatric symptoms in subjects with phenylketonuria (PKU ASCEND).. The primary objective of this study is to determine oxidative stress in patients with classical phenylketonuria (PKU) enrolled in PKU-016, using a brain scan (called an HMPAO SPECT) at baseline and 26 weeks, and blood redox biomarkers. ...
  https://clinicaltrials.gov/ct2/show/NCT01650909?term=PKU&recr=Open&rank=4
*  PKU (Phenylketonuria) - Diseases & Conditions | Med Log - Your Everyday Health Blog
The main phenylketonuria treatment is a strict diet with very limited intake of phenylalanine, which is mostly found in foods containing protein. Doctors used to believe it was OK for a person with PKU to stop the diet in adolescence, but today, doctors recommend sticking to the diet and PKU formula for life. Without PKU formula, your body can't get enough of essential nutrients called amino acids that are crucial for growth and general health. For example, the amino acid tyrosine is usually a byproduct of phenylalanine metabolism, a process that doesn't occur in people with PKU.. A safe amount of phenylalanine differs for each person. Your doctor will determine a safe amount through regular review of diet records, growth charts and blood levels of phenylalanine. Frequent blood tests will monitor PKU levels as they change over time, especially during childhood growth spurts and pregnancy. In general, the idea is to consume only the amount of phenylalanine that's necessary for normal growth ...
  http://medlog.info/pku-phenylketonuria-diseases-conditions-med-log/
*  Phenylketonuria (PKU): Screening and Management
INTRODUCTION Phenylketonuria or PKU is a rare, inherited metabolic disorder that, if untreated, causes mental retardation. Approximately one of every 10,000 infants in the United States is born with PKU, which usually results from a deficiency of a liver enzyme known as phenylalanine hydroxylase (PAH). This enzyme deficiency leads to elevated levels of the amino acid phenylalanine in the bloodstream. All infants in this country undergo blood testing for PKU. The current treatment for this disorder involves dietary modification. When a very strict diet is begun early and maintained, children with PKU can expect normal development and a normal lifespan. The diet generally excludes all high protein foods, such as meat, milk, eggs, and nuts, since all protein contains phenylalanine. Dietary noncompliance can result in a decline in mental and behavioral performance. Women with PKU must also maintain a strictly controlled diet before and during pregnancy to prevent fetal damage. Scientists are ...
  http://repositorio.ub.edu.ar/handle/123456789/2884
*  Neurocognitive Outcomes in Mild Hyperphenylalaninemia (MHP)MHP Study - Full Text View - ClinicalTrials.gov
Phenylketonuria (PKU) is a genetic disorder known to cause severe reduction in intelligence and deficits in cognitive function; it is associated with an elevated level of Phenylalanine (Phe) in blood.. Newborn screening and early treatment with restricted protein diet supplemented by a formula of amino-acids will preserve intelligence. In those with the severe form treated from birth, some deficits that affect higher functions of the brain are seen.. Given this, there is disagreement about how milder forms of this disease should be managed and what level of Phe is safe to be left untreated.. We seek to assess whether higher Phe levels, between 360 and 600µmol/L, are safe with respect to preservation of intelligence and higher cognitive functions. ...
  https://clinicaltrials.gov/ct2/show/NCT01924026?recr=Open&cond=%22Phenylketonurias%22&rank=15
*  A Pilot Study on Diurnal Variation - Full Text View - ClinicalTrials.gov
Phenylketonuria (PKU) is a rare genetic metabolic disease caused by a mutation that codes for an enzyme that converts the essential amino acid phenylalanine (Phe) into tyrosine. An absence or deficiency of this enzyme activity results in a Phe elevation, where higher Phe levels result in neurological damage. Diurnal variations of Phe levels have been observed in PKU patients in a 24-hour period.. As Kuvan has shown to stabilize Phe levels in PKU patients over time, our hypothesis is that this can be demonstrated within a 24-hour period of observation and indicate therefore that Kuvan may correlate with a lower plasma Phe variability. This study on PKU patients' diurnal variation will also provide important information as to the current method of blood Phe monitoring in a clinical setting to learn more about the optimal way to measure Phe concentration.. The study will last about 4 weeks (6 study visits) for the PKU participants and about 1 ...
  https://clinicaltrials.gov/ct2/show/NCT01806051?recr=Open&cond=%22Phenylketonurias%22&rank=14
*  A Pilot Study on Diurnal Variation - Full Text View - ClinicalTrials.gov
Phenylketonuria (PKU) is a rare genetic metabolic disease caused by a mutation that codes for an enzyme that converts the essential amino acid phenylalanine (Phe) into tyrosine. An absence or deficiency of this enzyme activity results in a Phe elevation, where higher Phe levels result in neurological damage. Diurnal variations of Phe levels have been observed in PKU patients in a 24-hour period.. As Kuvan has shown to stabilize Phe levels in PKU patients over time, our hypothesis is that this can be demonstrated within a 24-hour period of observation and indicate therefore that Kuvan may correlate with a lower plasma Phe variability. This study on PKU patients' diurnal variation will also provide important information as to the current method of blood Phe monitoring in a clinical setting to learn more about the optimal way to measure Phe concentration.. The study will last about 4 weeks (6 study visits) for the PKU participants and about 1 ...
  https://clinicaltrials.gov/ct2/show/NCT01806051?recr=Open&cond=%22Phenylketonurias%22&rank=18
*  A Phase 3, Multicenter, Open-Label Extension Study of Phenoptin in Subjects with Phenylketonuria Who Have Elevated...
This extension study is evaluating the safety and tolerability of long-term sapropterin in subjects with phenylketonuria who have elevated phenylalanine levels
  http://adisinsight.springer.com/trials/700247357
*  Genetic Diseases - Phenylketonuria / Eseja / ID: 974929
Eseja: Genetic Diseases - Phenylketonuria. Classical PKU (Phenyklketonuria) is an autonomic recessive disorder. It is caused by a shortage in the enzyme 'Phenyl
  https://www.atlants.lv/eseja/genetic-diseases-phenylketonuria/974929/
*  Long-term correction of murine phenylketonuria by viral gene transfer: liver versus muscle - Zurich Open Repository and Archive
Current therapy for phenylketonuria (PKU) consists of life-long dietary restriction of phenylalanine (Phe), which presents problems of adherence for patients. Alternative therapies under investigation include, among others, the use of gene therapy to provide copies of wild-type, non-mutant, phenylalanine hydroxylase (PAH) enzyme. Expression of PAH in both liver (the usual metabolic source of this enzyme) and skeletal muscle is under investigation. Liver gene therapy, using a viral vector based on the adeno-associated viruses (AAVs), provided effective clearance of serum Phe that was sustained for 1 year in some mice. In order for PAH expression to be effective in skeletal muscle, the essential metabolic cofactor, tetrahydrobiopterin (BH(4)), must also be provided, either by supplementation or gene therapy. Both these approaches were effective. When transgenic PKU mice that constitutively expressed PAH in muscle were given intraperitoneal supplementation with BH(4), this ...
  http://www.zora.uzh.ch/id/eprint/42424/
*  Study of a National Cohort of Adult Patients With Phenylketonuria - Full Text View - ClinicalTrials.gov
Phenylketonuria (PKU) is a metabolic disease of genetic origin. This is a rare disease (incidence 1 / 16000 births) which is the subject of a systematic neonatal screening in France, because it is treatable by a diet low in phenylalanine. This plan is required upon confirmation of diagnosis and continued until the age of 8 years. The current trend is to continue the scheme at least until adolescence. Unlike other countries, in France there are no recommendations for a plan 'for life'. Knowledge about the natural history of PKU in adulthood, the effects of pediatric age, the frequency of complicated shapes, and prognostic factors are poorly documented. On the other hand, there is no consensus on the therapeutic management of this disease in adulthood and monitoring that could be directed towards the detection of neurological disorders and nutrition. Social integration and quality of life of adults PKU patients living in France have not been studied ...
  https://clinicaltrials.gov/ct2/show/NCT01619722?term=PKU&recr=Open&rank=10
*  Study of a National Cohort of Adult Patients With Phenylketonuria - Full Text View - ClinicalTrials.gov
Phenylketonuria (PKU) is a metabolic disease of genetic origin. This is a rare disease (incidence 1 / 16000 births) which is the subject of a systematic neonatal screening in France, because it is treatable by a diet low in phenylalanine. This plan is required upon confirmation of diagnosis and continued until the age of 8 years. The current trend is to continue the scheme at least until adolescence. Unlike other countries, in France there are no recommendations for a plan 'for life'. Knowledge about the natural history of PKU in adulthood, the effects of pediatric age, the frequency of complicated shapes, and prognostic factors are poorly documented. On the other hand, there is no consensus on the therapeutic management of this disease in adulthood and monitoring that could be directed towards the detection of neurological disorders and nutrition. Social integration and quality of life of adults PKU patients living in France have not been studied ...
  https://clinicaltrials.gov/ct2/show/NCT01619722?term=PKU&recr=Open&rank=9
*  Kuvan®'s Effect on the Cognition of Children With Phenylketonuria - Full Text View - ClinicalTrials.gov
For subjects not treated with Kuvan®/BH4 at Screening: a response test has been performed during Screening or is available from the subject's medical records and satisfies the 3 following criteria: a decrease in blood phenylalanine levels of at least 30 percent was observed after at least 24 hours with a dose of at least 10 mg/kg/ ...
  https://clinicaltrials.gov/ct2/show/NCT01965912?term=Phenylketonuria&rank=9