Phenylketonurias: A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme PHENYLALANINE HYDROXYLASE or less frequently by reduced activity of DIHYDROPTERIDINE REDUCTASE (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; SEIZURES; skin HYPOPIGMENTATION; ECZEMA; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952).Phenylketonuria, Maternal: A condition occurring in untreated or partially treated females with PHENYLKETONURIA when they become pregnant. This may result in damages to the FETUS, including MICROCEPHALY; MENTAL RETARDATION; congenital heart disease; FETAL GROWTH RETARDATION; and CRANIOFACIAL ABNORMALITIES. (From Am J Med Genet 1997 Mar 3;69(1):89-95)Phenylalanine Hydroxylase: An enzyme of the oxidoreductase class that catalyzes the formation of L-TYROSINE, dihydrobiopterin, and water from L-PHENYLALANINE, tetrahydrobiopterin, and oxygen. Deficiency of this enzyme may cause PHENYLKETONURIAS and PHENYLKETONURIA, MATERNAL. EC 1.14.16.1.Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.Phenylpyruvic Acids: A group of compounds that are derivatives of phenylpyruvic acid which has the general formula C6H5CH2COCOOH, and is a metabolite of phenylalanine. (From Dorland, 28th ed)Biopterin: A natural product that has been considered as a growth factor for some insects.Neonatal Screening: The identification of selected parameters in newborn infants by various tests, examinations, or other procedures. Screening may be performed by clinical or laboratory measures. A screening test is designed to sort out healthy neonates (INFANT, NEWBORN) from those not well, but the screening test is not intended as a diagnostic device, rather instead as epidemiologic.Anabaena variabilis: A species of ANABAENA that can form SPORES called akinetes.Metabolism, Inborn Errors: Errors in metabolic processes resulting from inborn genetic mutations that are inherited or acquired in utero.Microcephaly: A congenital abnormality in which the CEREBRUM is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.)Infant, Newborn: An infant during the first month after birth.Diet Therapy: By adjusting the quantity and quality of food intake to improve health status of an individual. This term does not include the methods of food intake (NUTRITIONAL SUPPORT).Intelligence: The ability to learn and to deal with new situations and to deal effectively with tasks involving abstractions.Phenylalanine Ammonia-Lyase: An enzyme that catalyzes the deamination of PHENYLALANINE to form trans-cinnamate and ammonia.Homogentisic AcidCongenital Hypothyroidism: A condition in infancy or early childhood due to an in-utero deficiency of THYROID HORMONES that can be caused by genetic or environmental factors, such as thyroid dysgenesis or HYPOTHYROIDISM in infants of mothers treated with THIOURACIL during pregnancy. Endemic cretinism is the result of iodine deficiency. Clinical symptoms include severe MENTAL RETARDATION, impaired skeletal development, short stature, and MYXEDEMA.Intellectual Disability: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28)Diet, Protein-Restricted: A diet that contains limited amounts of protein. It is prescribed in some cases to slow the progression of renal failure. (From Segen, Dictionary of Modern Medicine, 1992)Galactosemias: A group of inherited enzyme deficiencies which feature elevations of GALACTOSE in the blood. This condition may be associated with deficiencies of GALACTOKINASE; UDPGLUCOSE-HEXOSE-1-PHOSPHATE URIDYLYLTRANSFERASE; or UDPGLUCOSE 4-EPIMERASE. The classic form is caused by UDPglucose-Hexose-1-Phosphate Uridylyltransferase deficiency, and presents in infancy with FAILURE TO THRIVE; VOMITING; and INTRACRANIAL HYPERTENSION. Affected individuals also may develop MENTAL RETARDATION; JAUNDICE; hepatosplenomegaly; ovarian failure (PRIMARY OVARIAN INSUFFICIENCY); and cataracts. (From Menkes, Textbook of Child Neurology, 5th ed, pp61-3)Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.

*  Phenylketonuria - SNPedia

PAH Phenylketonuria Pathogenic Mutations rsid 23andMe term synonyms (c. or p.) OMIM On chip? ... Phenylketonuria (PKU) was one of the first inherited metabolic diseases to be tested for in newborns. PKU is a rare enzyme ... Mutations were considered pathogenic for phenylketonuria based on being listed as pathogenic in ClinVar and/or having an ... Retrieved from "https://www.SNPedia.com/index.php?title=Phenylketonuria&oldid=1205036" ...
https://snpedia.com/index.php/Phenylketonuria

*  PKUDOS: Phenylketonuria (PKU) Demographic, Outcomes, and Safety Registry - Full Text View - ClinicalTrials.gov

PKUDOS: Phenylketonuria (PKU) Demographic, Outcomes, and Safety Registry (PKUDOS). This study is currently recruiting ... Phenylketonurias. Brain Diseases, Metabolic, Inborn. Brain Diseases, Metabolic. Brain Diseases. Central Nervous System Diseases ... Genetics Home Reference related topics: phenylketonuria tetrahydrobiopterin deficiency MedlinePlus related topics: ... Genetic and Rare Diseases Information Center resources: Phenylketonuria Inborn Amino Acid Metabolism Disorder ...
https://clinicaltrials.gov/ct2/show/NCT00778206?cond="phenylketonuria"&rank=8

*  The National Institutes of Health (NIH) Consensus Development Program: Phenylketonuria: Screening and Management

Phenylketonuria: Screening and Management. National Institutes of Health. Consensus Development Conference Statement. October ... Classical phenylketonuria (PKU) is a rare metabolic disorder (and orphan disease) that usually results from a deficiency of a ... 113 in the electronic form displayed here, it is recommended that the following format be used: Phenylketonuria: Screening and ... Phenylketonuria Scientific Review Conference: State of the Science and Future Research Needs (2014) ...
https://consensus.nih.gov/2000/2000Phenylketonuria113html.htm

*  Study to Evaluate the Effects of Kuvan on Individuals With Phenylketonuria (PKU) With Maladaptive Behaviors - Full Text View -...

MedlinePlus related topics: Phenylketonuria Genetic and Rare Diseases Information Center resources: Phenylketonuria Inborn ... Study to Evaluate the Effects of Kuvan on Individuals With Phenylketonuria (PKU) With Maladaptive Behaviors. This study has ... Phenylketonurias. Brain Diseases, Metabolic, Inborn. Brain Diseases, Metabolic. Brain Diseases. Central Nervous System Diseases ... Pilot Study to Evaluate the Effects of Kuvan on Adult Individuals With Phenylketonuria With Measurable Maladaptive Behaviors. ...
https://clinicaltrials.gov/ct2/show/NCT00728676?term=Phenylketonuria&rank=17

*  Genetical heterogeneity of phenylketonuria

Genetic heterogeneity of phenylketonuria, dependent on polylocus control of phenylalanine hydroxylase complex, is considered in ... Abstract: Data on genetic nature of phenylketonuria molecular mechanisms of its pathogenesis and approaches to treatment and ... A possibility is discussed of the existence of the genetically different forms of phenylketonuria. Data on the molecular ... Reference: Annenkov G.A., Genetical heterogeneity of phenylketonuria, Voprosy meditsinskoi khimii, 1982, vol: 28(3), 62-70. ...
pbmc.ibmc.msk.ru/index.php/en/article/PBMC-1982-28-3-62-en

*  Phenylketonuria (PKU): Screening and Management

INTRODUCTION Phenylketonuria or PKU is a rare, inherited metabolic disorder that, if untreated, causes mental retardation. ... Consensus Development Conference titled Phenylketonuria (PKU): Screening and Management held in Bethesda, MD on October 16-18, ...
repositorio.ub.edu.ar/handle/123456789/2884

*  DMOZ - Health: Conditions and Diseases: Nutritional and Metabolic Disorders: Inherited: Phenylketonuria

Phenylketonuria (PKU) is a genetic disorder that is characterized by an inability of the body to utilize the essential amino ... NHS Choices: Phenylketonuria Provides information on this condition which is caused by the body being unable to break down ... Phenylketonuria (PKU) is a genetic disorder that is characterized by an inability of the body to utilize the essential amino ...
dmoztools.net/Health/Conditions_and_Diseases/Nutritional_and_Metabolic_Disorders/Inherited/Phenylketonuria/

*  Genetic disorder - Wikipedia

Phenylketonuria. 1 in 12,000. Mucopolysaccharidoses. 1 in 25,000. Lysosomal acid lipase deficiency. 1 in 40,000. ...
https://en.wikipedia.org/wiki/Hereditary_disease

*  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 ... Speed of processing and executive functions in adults with phenylketonuria: quick in finding the word, but not the ladybird. ... Cognitive outcomes in early-treated adults with phenylketonuria Rights statement: This article has been published under the ... Cognitive outcomes in early-treated adults with phenylketonuria (PKU): a comprehensive picture across domains. Research output ...
https://research.aston.ac.uk/portal/en/researchoutput/cognitive-outcomes-in-earlytreated-adults-with-phenylketonuria-pku

*  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 ... Phenylketonurias. Brain Diseases, Metabolic, Inborn. Brain Diseases, Metabolic. Brain Diseases. Central Nervous System Diseases ... Genetics Home Reference related topics: phenylketonuria tetrahydrobiopterin deficiency MedlinePlus related topics: ... Genetic and Rare Diseases Information Center resources: Phenylketonuria Inborn Amino Acid Metabolism Disorder ...
https://clinicaltrials.gov/ct2/show/NCT01806051?recr=Open&cond="Phenylketonurias"&rank=18

*  The time consuming nature of phenylketonuria: A cross-sectional study investigating time burden and costs of phenylketonuria in...

The time consuming nature of phenylketonuria: A cross-sectional study investigating time burden and costs of phenylketonuria in The Netherlands. | Mapi: Health Research & Commercialization
mapigroup.com/publications/rare-diseases/time-consuming-nature-phenylketonuria-cross-sectional-study-investigating-time-burden-costs-phenylketonuria-netherlands-2/

*  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
adisinsight.springer.com/trials/700247357

*  The personal burden for caregivers of children with phenylketonuria: A cross-sectional study investigating time burden and...

The personal burden for caregivers of children with phenylketonuria: A cross-sectional study investigating time burden and costs in the UK. | Mapi: Health Research & Commercialization
mapigroup.com/publications/rare-diseases/personal-burden-caregivers-children-phenylketonuria-cross-sectional-study-investigating-time-burden-costs-uk/

*  Chesnokova M A - Pharmacoeconomics: theory and practice

Phenylketonuria is a hereditary disease associated with a metabolic disorder of amino acids in the organism, the prevalence of which in the Russian Federation is 1:10000. Currently, the main treatment of phenylketonuria is diet therapy with specialized health food (a mixture of amino acids without phenylalanine). This research presents the results of a comparison of diet therapy with medicinal mixtures of MDmil PKU line taken from the first month of life of a child compared to food of other producers, taken in later periods. Efficiency analysis is based on data provided by the major regional genetics specialists from 24 regions of the Russian Federation on treatment of 1088 children suffering from phenylketonuria. Cost analysis of treatment of patients with PKU until their majority reveals least expensive diet therapy initiated from the first month of life with specialized health food of MDmil PKU line compared with diet, started in later periods with specialized products of different ...
pharmacoeconom.com/en/authors/authors_297.html

*  Clinical Trials sub-cluster 88

BACKGROUND: The 24- and 48-hour tetrahydrobiopterin (BH4) loading test (BLT) performed at a minimum baseline phenylalanine concentration of 400μmol/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 400μmol/l minimum baseline phenylalanine ...
biomedsearch.com/cluster/19/Clinical-Trials/sub-88-p6.html

*  Woman has rare genetic condition making her allergic to protein | Daily Mail Online

PhD student Kreseda Smith (pictured), 36, suffers from phenylketonuria (PKU) which means a build-up of protein could leave her with devastating brain and muscle damage.
dailymail.co.uk/news/article-2817838/Eating-burger-chips-leave-brain-damaged-Patient-36-rare-genetic-condition-making-allergic-protein.html

*  Neuro-Audio-Screen | Misr For Trade

The hearing impairment is diagnosed in three of every thousand babies born, that is twice more than frequency of cleft lip (palate), twice more than frequency of Down's syndrome and ten times more than frequency of phenylketonuria.. The problem of diagnostics and treatment of hearing loss and deafness in this special category of patients is actual both in medical and social relations. Often the visual examination and other traditional diagnostic techniques of hearing impairment detection do not reveal the problem until 1 to 3 years of age - which is well beyond the critical period (6 months) for healthy speech and language development.. However, if a hearing impairment is identified and treated in its early stages, studies have shown that the child's speech and language skills will be comparable to his or her normal-hearing peers. For these reasons, hearing screening at birth and routinely throughout childhood is extremely important. Timely and correct diagnosis provides an opportunity to start ...
misrfortrade.com/product/neuro-audio-screen/

Hyperphenylalaninemia: (also includes non-classic PKU)Phenylalanine N-monooxygenase: Phenylalanine N-monooxygenase (, phenylalanine N-hydroxylase, CYP79A2) is an enzyme with system name L-phenylalanine,NADPH:oxygen oxidoreductase (N-hydroxylating). This enzyme catalyses the following chemical reactionIvar Asbjørn Følling: Ivar Asbjørn Følling (23 August 1888 – 24 January 1973) was a Norwegian physician and biochemist who first described the disease named after him—Følling's disease—which is better known outside of Norway as phenylketonuria or, for short, PKU. He was born in Kvam, Steinkjer.BiopterinAnabaena variabilis: Anabaena variabilis is a species of filamentous cyanobacterium. This species of the genus Anabaena and the domain Eubacteria is capable of photosynthesis.Journal of Inherited Metabolic Disease: The Journal of Inherited Metabolic Disease is a peer-reviewed medical journal covering inherited metabolic disorders. It was established in 1978 and is the official journal of the Society for the Study of Inborn Errors of Metabolism.Microcephaly lymphoedema chorioretinal dysplasia: Microcephaly lymphoedema chorioretinal dysplasia (MLCRD) is a genetic condition associated with:Evolution of human intelligence: The evolution of human intelligence refers to a set of theories that attempt to explain how human intelligence has evolved and are closely tied to the evolution of the human brain and to the origin of language.Elicitor: Elicitors in plant biology are extrinsic, or foreign, molecules often associated with plant pests, diseases or synergistic organisms. Elicitor molecules can attach to special receptor proteins located on plant cell membranes.Alkaptonuria: (ILDS E70.210)Congenital hypothyroidismHyperphosphatasia with mental retardation syndrome: Hyperphosphatasia with mental retardation syndrome, HPMRS, also known as Mabry syndrome, has been described in patients recruited on four continents world-wide. Mabry syndrome was confirmed to represent an autosomal recessive syndrome characterized by severe mental retardation, considerably elevated serum levels of alkaline phosphatase, hypoplastic terminal phalanges, and distinct facial features that include: hypertelorism, a broad nasal bridge and a rectangular face.Low-protein diet: A low-protein diet is a diet in which people reduce their intake of protein. A low-protein diet is prescribed for those with inherited metabolic disorders, such as Phenylketonuria and Homocystinuria and reduced protein levels have been used by people with kidney or liver disease.GalactosemiaNon-receptor tyrosine kinase: Non-receptor tyrosine kinases (nRTKs) are cytoplasmic enzymes that are responsible for catalysing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in proteins. Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation).

(1/423) A different approach to treatment of phenylketonuria: phenylalanine degradation with recombinant phenylalanine ammonia lyase.

Phenylketonuria (PKU), with its associated hyperphenylalaninemia (HPA) and mental retardation, is a classic genetic disease and the first to have an identified chemical cause of impaired cognitive development. Treatment from birth with a low phenylalanine diet largely prevents the deviant cognitive phenotype by ameliorating HPA and is recognized as one of the first effective treatments of a genetic disease. However, compliance with dietary treatment is difficult and when it is for life, as now recommended by an internationally used set of guidelines, is probably unrealistic. Herein we describe experiments on a mouse model using another modality for treatment of PKU compatible with better compliance using ancillary phenylalanine ammonia lyase (PAL, EC 4.3.1.5) to degrade phenylalanine, the harmful nutrient in PKU; in this treatment, PAL acts as a substitute for the enzyme phenylalanine monooxygenase (EC 1.14.16.1), which is deficient in PKU. PAL, a robust enzyme without need for a cofactor, converts phenylalanine to trans-cinnamic acid, a harmless metabolite. We describe (i) an efficient recombinant approach to produce PAL enzyme, (ii) testing of PAL in orthologous N-ethyl-N'-nitrosourea (ENU) mutant mouse strains with HPA, and (iii) proofs of principle (PAL reduces HPA)-both pharmacologic (with a clear dose-response effect vs. HPA after PAL injection) and physiologic (protected enteral PAL is significantly effective vs. HPA). These findings open another way to facilitate treatment of this classic genetic disease.  (+info)

(2/423) A model of human phenylalanine metabolism in normal subjects and in phenylketonuric patients.

The derivation of a quantitative model of phenylalanine metabolism in humans is described. The model is based on the kinetic properties of pure recombinant human phenylalanine hydroxylase and on estimates of the in vivo rates of phenylalanine transamination and protein degradation. Calculated values for the steady-state concentration of blood phenylalanine, rate of clearance of phenylalanine from the blood after an oral load of the amino acid, and dietary tolerance of phenylalanine all agree well with data from normal as well as from phenylketonuric patients and obligate heterozygotes. These calculated values may help in the decision about the degree of restriction of phenylalanine intake that is necessary to achieve a satisfactory clinical outcome in classical patients and in those with milder forms of the disease.  (+info)

(3/423) Biopterin derivatives in normal and phenylketonuric patients after oral loads of L-phenylalanine, L-tyrosine, and L-tryptophan.

Plasma biopterin derivatives studied in 10 normal and 21 phenylketonuric children showed a significantly high concentration in the latter group. Biopterin derivatives correlated with plasma phenylalanine concentration, but in normal adults given an oral phenylalanine load the rate of increase with phenylalanine differed from that in phenylketonuric patients. A patient with hyperphenylalaninaemia, not due to phenylketonuria, had an abnormal biopterin derivatives response to phenylalanine distinct from that of patients with classical phenylketonuria. This may be a useful investigation to differentiate some variants of phenylketonuria.  (+info)

(4/423) Haplotypes and mutations of the PAH locus in Egyptian families with PKU.

A high degree of molecular heterogeneneity at the phenylalanine hydroxylase (PAH) locus was established by examining RFLP haplotypes and PAH mutations in the families of 13 Egyptians with phenylketenouria (PKU). Thirteen different haplotypes were unequivocally determined in these kindreds. Haplotypes 1.8, 3.9, 4.3, 7.8, 22.11, 27.6, and 52.8 were found segregating with normal chromosomes, whilst haplotypes 1.8, 5.9, 23.8, 32.8, the newly assigned 73.9, and two as yet incomplete but novel haplotypes were found segregating with the mutant chromosomes. There was no particular preference for a single haplotype among normal or mutant chromosomes. Nine different mutations were also identified among the 26 alleles. IVS 10nt11g (8/26), IVS 2nt5g-c (4/26), R261Q (3/26), R176X (2/26), Y206D (2/26), S231P (2/26), Y198fs [593-614del22bp]; (2/26), G46fs [136/137delG]; (1/26), and E178G (1/26). Six of these mutations (IVS 2nt5g-c, R176X, Y198fs, R261Q, S231P, and IVS 10nt11g) are common to other Mediterranean populations. Two mutations not previously reported in the Mediterranean basin were also observed (Y206D and G46fs). These intriguing preliminary findings confirm IVS 10nt11g as a major mutation among Mediterranean mutations and demonstrate the need for a more comprehensive study of Arab populations to confirm the uniqueness of the two novel mutations to the Egyptian population.  (+info)

(5/423) Effects of dietary mixtures of amino acids on fetal growth and maternal and fetal amino acid pools in experimental maternal phenylketonuria.

BACKGROUND: Branched-chain amino acids have been reported to improve fetal brain development in a rat model in which maternal phenylketonuria (PKU) is induced by the inclusion of an inhibitor of phenylalanine hydroxylase, DL-p-chlorophenylalanine, and L-phenylalanine in the diet. OBJECTIVE: We studied whether a dietary mixture of several large neutral amino acids (LNAAs) would improve fetal brain growth and normalize the fetal brain amino acid profile in a rat model of maternal PKU induced by DL-alpha-methylphenylalanine (AMPhe). DESIGN: Long-Evans rats were fed a basal diet or a similar diet containing 0.5% AMPhe + 3.0% L-phenylalanine (AMPhe + Phe diet) from day 11 until day 20 of gestation in experiments to test various mixtures of LNAAs. Maternal weight gains and food intakes to day 20, fetal body and brain weights at day 20, and fetal brain and fetal and maternal plasma amino acid concentrations at day 20 were measured. RESULTS: Concentrations of phenylalanine and tyrosine in fetal brain and in maternal and fetal plasma were higher and fetal brain weights were lower in rats fed the AMPhe + Phe diet than in rats fed the basal diet. However, fetal brain growth was higher and concentrations of phenylalanine and tyrosine in fetal brain and in maternal and fetal plasma were lower in rats fed the AMPhe + Phe diet plus LNAAs than in rats fed the diet containing AMPhe + Phe alone. CONCLUSION: LNAA supplementation of the diet improved fetal amino acid profiles and alleviated most, but not all, of the depression in fetal brain growth observed in this model of maternal PKU.  (+info)

(6/423) Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria.

Large neutral amino acids (LNAAs), including phenylalanine (Phe), compete for transport across the blood-brain barrier (BBB) via the L-type amino acid carrier. Accordingly, elevated plasma Phe impairs brain uptake of other LNAAs in patients with phenylketonuria (PKU). Direct effects of elevated brain Phe and depleted LNAAs are probably major causes for disturbed brain development and function in PKU. Competition for the carrier might conversely be put to use to lower Phe influx when the plasma concentrations of all other LNAAs are increased. This hypothesis was tested by measuring brain Phe in patients with PKU by quantitative 1H magnetic resonance spectroscopy during an oral Phe challenge with and without additional supplementation with all other LNAAs. Baseline plasma Phe was approximately 1,000 micromol/l and brain Phe was approximately 250 micromol/l in both series. Without LNAA supplementation, brain Phe increased to approximately 400 micromol/l after the oral Phe load. Electroencephalogram (EEG) spectral analysis revealed acutely disturbed brain activity. With concurrent LNAA supplementation, Phe influx was completely blocked and there was no slowing of EEG activity. These results are relevant for further characterization of the LNAA carrier and of the pathophysiology underlying brain dysfunction in PKU and for treatment of patients with PKU, as brain function might be improved by continued LNAA supplementation.  (+info)

(7/423) Genetic and phenotypic aspects of phenylalanine hydroxylase deficiency in Spain: molecular survey by regions.

We present an extensive study of the genetic diversity of phenylalanine hydroxylase deficiency in the Spanish phenylketonuria population. We have analysed 195 PKU patients by DGGE analysis identifying 67 different mutations which represent 89% of the total mutant chromosomes. Seventeen mutations first described in Spain have not yet been detected elsewhere; ten of these are reported here for the first time. The clinical significance of this high genetic heterogeneity was examined by analysing the genotype-phenotype correlations, mainly focusing on the mild hyperphenylalaninaemia (MHP) phenotype. The genotypes found in a group of 93 MHP patients, the largest analysed so far, are described in detail, as well as the relative frequencies of the MHP mutations identified. From the total pool of mutations, 27 can be considered severe, 18 can be defined as mild and 13 as associated with MHP. The prevalent mutations correspond to one severe mutation (IVS10nt-11), one MHP mutation (A403V) and two mild mutations (165T and V388M). The high frequency of mutations with a low degree of severity can explain the relatively higher prevalence of MHP and mild PKU phenotypes in Spain compared with NOrthern European populations. We have looked at the geographical distribution in Spain of the more common mutations, finding evidence of local mutation clustering, which could be the result of differences in the ethnic background and/or of genetic drift within each region.  (+info)

(8/423) Review: emotional and behavioral functioning in phenylketonuria.

OBJECTIVE: To examine 17 studies of the psychological sequelae of early-treated phenylketonuria (PKU) with emphasis on the impact of dietary control on functioning. Two questions are addressed: (1) What is the typical psychological profile associated with PKU? (2) Is emotional and behavioral disturbance more prevalent in PKU-affected individuals compared to appropriate controls? METHOD: Computerized searches of PsycINFO identified studies using behavioral, personality, and diagnostic measures. RESULTS: Findings converge upon a profile including attentional difficulties, depression, anxiety, and low self-esteem. Methodological constraints limit conclusions regarding the nature and severity of observed difficulties. A single study has used comparison groups appropriate for the simultaneous examination of the questions posed (Waisbren and Levy, 1991). CONCLUSIONS: We discuss results using a biopsychosocial framework, addressing the factors and processes that may influence emotional and behavioral functioning in this neurodevelopmental disorder. We outline potential lines of new investigation that address critical methodological factors.  (+info)



phenylalanine


  • Classical phenylketonuria (PKU) is a rare metabolic disorder (and orphan disease) that usually results from a deficiency of a liver enzyme known as phenylalanine hydroxylase (PAH). (nih.gov)
  • Genetic heterogeneity of phenylketonuria, dependent on polylocus control of phenylalanine hydroxylase complex, is considered in detail. (msk.ru)
  • Phenylketonuria (PKU) is a genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. (dmoztools.net)
  • 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. (aston.ac.uk)
  • This self-controlled, prospective, pilot study is designed to gather information regarding the diurnal variation (changes that occur each day) in the levels of plasma phenylalanine (Phe) and tyrosine in patients with phenylketonuria (PKU) and in the non-PKU population. (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. (clinicaltrials.gov)
  • Phenylketonuria is a rare disorder in which the enzyme required to properly utilize phenylalanine is missing. (progressivehealth.com)
  • Because phenylalanine is naturally found in breast milk, phenylketonuria must be caught early on in newborns. (progressivehealth.com)
  • Children and adults with phenylketonuria are advised to avoid foods and supplements rich in phenylalanine. (progressivehealth.com)

Screening and Management


  • This statement was originally published as: Phenylketonuria: Screening and Management. (nih.gov)
  • For making bibliographic reference to consensus statement no. 113 in the electronic form displayed here, it is recommended that the following format be used: Phenylketonuria: Screening and Management. (nih.gov)
  • This bibliography was prepared in support of the National Institutes of Health (NIH) Consensus Development Conference titled Phenylketonuria (PKU): Screening and Management held in Bethesda, MD on October 16-18, 2000. (ub.edu.ar)

Kuvan


  • Patients with a confirmed diagnosis of Phenylketonuria (PKU) with hyperphenylalaninemia who have either received Kuvan therapy, or currently receive Kuvan therapy, or intend to begin receiving Kuvan therapy within 90 days of entering the registry. (clinicaltrials.gov)
  • To validate the outcome measures and the tolerability of Kuvan treatment in the improvement of behavioral symptoms in 10 selected adults with Phenylketonuria (PKU) with or without mental retardation. (clinicaltrials.gov)

Genetic


  • Data on genetic nature of phenylketonuria molecular mechanisms of its pathogenesis and approaches to treatment and prophylaxis of the disease are reviewed. (msk.ru)

rare


  • INTRODUCTION Phenylketonuria or PKU is a rare, inherited metabolic disorder that, if untreated, causes mental retardation. (ub.edu.ar)

affects