関: maternal PKU

WordNet

relating to or derived from ones mother; "maternal genes"
characteristic of a mother; "warm maternal affection for her guest"- Dorothy Sayers
a genetic disorder of metabolism; lack of the enzyme needed to turn phenylalanine into tyrosine results in an accumulation of phenylalanine in the body fluids which causes various degrees of mental deficiency (同)PKU

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母らしい;母の / 母方の

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/26 22:17:22」(JST)

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Phenylketonuria (PKU) is an inborn error of metabolism involving impaired metabolism of phenylalanine, one of the amino acids. Phenylketonuria is caused by absent or virtually absent phenylalanine hydroxylase (PAH) enzyme activity.

Protein-rich foods or the sweetener aspartame can act as poisons for people with phenylketonuria. The role of PAH is to break down excess phenylalanine from food. Phenylalanine is a necessary part of the human diet and is naturally present in all kinds of dietary protein. It is also used to make aspartame, known by the trade name Nutrasweet, which is used to sweeten low-calorie and sugar free soft drinks, yogurts, and desserts. In people without PKU, the PAH enzyme breaks down any excess phenylalanine from these sources beyond what is needed by the body. However, if there is not enough of the PAH enzyme or its cofactor, then phenylalanine can build up in the blood and brain to toxic levels, affecting brain development and function. PKU is rare, but important to identify, because if caught early it is very treatable. It is not contagious, and it is lifelong, but with early diagnosis and consistent treatment, the damaging effects can be minimal or non-existent.^[1]

Untreated PKU can lead to intellectual disability, seizures, and other serious medical problems.^[2] The best proven treatment for classical PKU patients is a strict phenylalanine-restricted diet supplemented by a medical formula containing amino acids and other nutrients.^[3] In the United States, the current recommendation is that the PKU diet should be maintained for life.^[4] Patients who are diagnosed early and maintain a strict diet can have a normal life span with normal mental development.

PKU is an inherited disease. When an infant is diagnosed with PKU, it is never the result of any action of the parents or any environmental factor. Rather, for a child to inherit PKU, both of his or her parents must have at least one mutated allele of the PAH gene. Most parents who are carriers of PKU genes are not aware that they have this mutation because being a carrier causes no medical problems. To be affected by PKU, a child must inherit two mutated alleles, one from each parent.

Genetic cause

Phenylketonuria is inherited in an autosomal recessive fashion

PKU is an autosomal recessive metabolic genetic disorder. As an autosomal recessive disorder, two PKU alleles are required for an individual to exhibit symptoms of the disease. If both parents are carriers for PKU, there is a 25% chance any child they have will be born with the disorder, a 50% chance the child will be a carrier, and a 25% chance the child will neither develop nor be a carrier for the disease.

PKU is characterized by homozygous or compound heterozygous mutations in the gene for the hepatic enzyme phenylalanine hydroxylase (PAH), rendering it nonfunctional.^[5]^:541 This enzyme is necessary to metabolize the amino acid phenylalanine (Phe) to the amino acid tyrosine (Tyr). When PAH activity is reduced, phenylalanine accumulates and is converted into phenylpyruvate (also known as phenylketone), which can be detected in the urine.^[6]

Carriers of a single PKU allele do not exhibit symptoms of the disease but appear to be protected to some extent against the fungal toxin ochratoxin A.^[7] This accounts for the persistence of the allele in certain populations in that it confers a selective advantage—in other words, being a heterozygote is advantageous.^[8]

The PAH gene is located on chromosome 12 in the bands 12q22-q24.1. More than 400 disease-causing mutations have been found in the PAH gene. This is an example of allelic genetic heterogeneity.

Phenylketonuria can exist in mice, which have been extensively used in experiments into finding an effective treatment for it.^[9] The macaque monkey's genome was recently sequenced, and the gene encoding phenylalanine hydroxylase was found to have a sequence that, in humans, would be considered a PKU mutation.^[10]

History

Before the causes of PKU were understood, PKU caused severe disability in most people who inherited the relevant mutations. Nobel and Pulitzer Prize winning author Pearl S. Buck had a daughter named Carol who lived with PKU before treatment was available, and wrote a moving account of its effects in a book called The Child Who Never Grew.^[11] Many untreated PKU patients born before widespread newborn screening are still alive, largely in dependent living homes/institutions.^[12]

Phenylketonuria was discovered by the Norwegian physician Ivar Asbjørn Følling in 1934^[13] when he noticed hyperphenylalaninemia (HPA) was associated with intellectual disability. In Norway, this disorder is known as Følling's disease, named after its discoverer.^[14] Dr. Følling was one of the first physicians to apply detailed chemical analysis to the study of disease.

In 1934 at Rikshospitalet, Dr. Følling saw a young woman named Borgny Egeland. She had two children, Liv and Dag, who had been normal at birth but subsequently developed intellectual disability. When Dag was about a year old, the mother noticed a strong smell to his urine. Dr. Følling obtained urine samples from the children and, after many tests, he found that the substance causing the odor in the urine was phenylpyruvic acid. The children, he concluded, had excess phenylpyruvic acid in the urine, the condition which came to be called phenylketonuria (PKU).^[6]

His careful analysis of the urine of the two affected siblings led him to request many physicians near Oslo to test the urine of other affected patients. This led to the discovery of the same substance he had found in eight other patients. He conducted tests and found reactions that gave rise to benzaldehyde and benzoic acid, which led him to conclude that the compound contained a benzene ring. Further testing showed the melting point to be the same as phenylpyruvic acid, which indicated that the substance was in the urine. His careful science inspired many to pursue similar meticulous and painstaking research with other disorders.^{[citation needed]}

PKU was the first disorder to be routinely diagnosed through widespread newborn screening. Robert Guthrie introduced the newborn screening test for PKU in the early 1960s.^[15] With the knowledge that PKU could be detected before symptoms were evident, and treatment initiated, screening was quickly adopted around the world. Austria started screening for PKU in 1966^[16] and England in 1968.^[17]

Screening and presentation

Blood is taken from a two-week-old infant to test for phenylketonuria

PKU is commonly included in the newborn screening panel of most countries, with varied detection techniques. Most babies in developed countries are screened for PKU soon after birth.^[18] Screening for PKU is done with bacterial inhibition assay (Guthrie test), immunoassays using fluorometric or photometric detection, or amino acid measurement using tandem mass spectrometry (MS/MS). Measurements done using MS/MS determine the concentration of Phe and the ratio of Phe to tyrosine, the ratio will be elevated in PKU.^[19]

Because the mother's body is able to break down phenylalanine during pregnancy, infants with PKU are normal at birth. The disease is not detectable by physical examination at that time, because no damage has yet been done. However, a blood test can reveal elevated phenylalanine levels after one or two days of normal infant feeding. This is the purpose of newborn screening, to detect the disease with a blood test before any damage is done, so that treatment can prevent the damage from happening.

If a child is not diagnosed during the routine newborn screening test (typically performed 2–7 days after birth, using samples drawn by neonatal heel prick), and a phenylalanine restricted diet is not introduced, then phenylalanine levels in the blood will increase over time. Toxic levels of phenylalanine (and insufficient levels of tyrosine) can interfere with infant development in ways which have permanent effects. The disease may present clinically with seizures, hypopigmentation (excessively fair hair and skin), and a "musty odor" to the baby's sweat and urine (due to phenylacetate, a carboxylic acid produced by the oxidation of phenylketone). In most cases, a repeat test should be done at approximately two weeks of age to verify the initial test and uncover any phenylketonuria that was initially missed.

Untreated children often fail to attain early developmental milestones, develop microcephaly, and demonstrate progressive impairment of cerebral function. Hyperactivity, EEG abnormalities, and seizures, and severe learning disabilities are major clinical problems later in life. The characteristic "musty or mousy" odor of skin as well as a tendency towards and eczema, also persist throughout life without treatment.

The damage done to the brain if PKU is untreated during the first months of life is not reversible. It is critical to control the diet of infants with PKU very carefully so that brain has an opportunity to develop normally. Affected children who are detected at birth and treated are much less likely to develop neurological problems or have seizures and intellectual disability (though such clinical disorders are still possible.)

In general, however, outcomes for treated PKU patients are good. Treated PKU patients may have no detectable physical, neurological, or developmental problems at all. Many adults with PKU who were diagnosed through newborn screening and have been treated since birth have high educational achievement, successful careers, and fulfulling family lives.^[20]^[21]

Pathophysiology

Classical PKU and Hyperphenylalaninemia

Classical PKU, and its less severe forms "mild PKU" and "mild hyperphenylalaninemia" are caused by a mutated gene for the enzyme phenylalanine hydroxylase (PAH), which converts the amino acid phenylalanine ("Phe") to other essential compounds in the body, in particular tyrosine. Tyrosine is a conditionally essential Amino acid for PKU patients because without PAH it cannot be produced in the body through the breakdown of phenylalanine. Tyrosine is necessary for the production of neurotransmitters like epinephrine, norepinephrine, and dopamine.^[22]

PAH deficiency causes a spectrum of disorders, including classic phenylketonuria (PKU) and mild hyperphenylalaninemia (also known as "hyperphe" or "mild HPA"), a less severe accumulation of phenylalanine. Patients with "hyperphe" may have more functional PAH enzyme and be able to tolerate larger amounts of phenylalanine in their diets than those with classic PKU, but unless dietary intake is at least somewhat restricted, their blood Phe levels are still higher than the levels in people with normal PAH activity.^[23]

Phenylalanine is a large, neutral amino acid (LNAA). LNAAs compete for transport across the blood–brain barrier (BBB) via the large neutral amino acid transporter (LNAAT). If phenylalanine is in excess in the blood, it will saturate the transporter. Excessive levels of phenylalanine tend to decrease the levels of other LNAAs in the brain. As these amino acids are necessary for protein and neurotransmitter synthesis, Phe buildup hinders the development of the brain, causing intellectual disability.^[24]

Recent research suggests that neurocognitive, psychosocial, quality of life, growth, nutrition, bone pathology are slightly suboptimal even for patients who are treated and maintain their Phe levels in the target range, if their diet is not supplemented with other amino acids.^[25]

Classic PKU dramatically affects myelination and white matter tracts in untreated in infants; this may be one major cause of neurological disorders associated with phenylketonuria. Differences in white matter development are observable with magnetic resonance imaging. Abnormalities in gray matter can also be detected, particularly in the motor and pre-motor cortex, thalamus and the hippocampus.^[26]

It was recently suggested that PKU may resemble amyloid diseases, such as Alzheimer's disease and Parkinson's disease, due to the formation of toxic amyloid-like assemblies of phenylalanine.^[27]

Other non-PAH mutations can also cause PKU.

Tetrahydrobiopterin-deficient hyperphenylalaninemia

A rarer form of hyperphenylalaninemia occurs when the PAH enzyme is normal, but a defect is found in the biosynthesis or recycling of the cofactor tetrahydrobiopterin (BH₄).^[28] BH₄ (called biopterin) is necessary for proper activity of the enzyme PAH, and this coenzyme can be supplemented as treatment. Those who suffer from this form of hyperphenylalaninemia may also have a deficiency of tyrosine (which is created from phenylalanine by PAH). These patients must also be supplemented with tyrosine to account for this deficiency.

Dihydrobiopterin reductase activity is needed to replenish quinonoid-dihydrobiopterin back into its tetrahydrobiopterin form, which is an important cofactor in many reactions in amino acid metabolism. Those with this deficiency may produce sufficient levels of the enzyme phenylalanine hydroxylase (PAH), but since tetrahydrobiopterin is a cofactor for PAH activity, deficient dihydrobiopterin reductase renders any PAH produced unable to use phenylalanine to produce tyrosine. Tetrahydrobiopterin is also a cofactor in the production of L-DOPA from tyrosine and 5-hydroxy-L-tryptophan from tryptophan, which must also be supplemented as treatment in addition to the supplements for classical PKU.

Levels of dopamine can be used to distinguish between these two types. Tetrahydrobiopterin is required to convert Phe to Tyr, but is also required to convert Tyr to L-DOPA via the enzyme tyrosine hydroxylase. L-DOPA in turn is converted to dopamine. Low levels of dopamine lead to high levels of prolactin. By contrast, in classical PKU (without dihydrobiopterin involvement), prolactin levels would be relatively normal.

Tetrahydrobiopterin deficiency can be caused by defects in four different genes. These types are known as HPABH4A, HPABH4B, HPABH4C, and HPABH4D.^[29]

Metabolic pathways

Pathophysiology of phenylketonuria, which is due to the absence of functional phenylalanine hydroxylase (classical subtype) or functional enzymes for the recycling of tetrahydrobiopterin (new variant subtype) utilized in the first step of the metabolic pathway.

The enzyme phenylalanine hydroxylase normally converts the amino acid phenylalanine into the amino acid tyrosine. If this reaction does not take place, phenylalanine accumulates and tyrosine is deficient. Excessive phenylalanine can be metabolized into phenylketones through the minor route, a transaminase pathway with glutamate. Metabolites include phenylacetate, phenylpyruvate and phenethylamine.^[30] Elevated levels of phenylalanine in the blood and detection of phenylketones in the urine is diagnostic, however most patients are diagnosed via newborn screening.

Treatment

PKU is not curable. However, if PKU is diagnosed early enough, an affected newborn can grow up with normal brain development by managing and controlling phenylalanine ("Phe") levels through diet, or a combination of diet and medication.

When Phe cannot be metabolized by the body, a typical diet that would be healthy for people without PKU causes abnormally high levels of Phe to accumulate in the blood, which is toxic to the brain. If left untreated, complications of PKU include severe intellectual disability, brain function abnormalities, microcephaly, mood disorders, irregular motor functioning, and behavioral problems such as attention deficit hyperactivity disorder, as well as physical symptoms such as a "musty" odor, eczema, and unusually light skin and hair coloration. In contrast, PKU patients who follow the prescribed dietary treatment from birth, may have no symptoms at all. Their PKU would be detectable only by a blood test.

To achieve these good outcomes, all PKU patients must adhere to a special diet low in Phe for optimal brain development. Since Phe is necessary for the synthesis of many proteins, it is required for appropriate growth, but levels must be strictly controlled in PKU patients.

PKU is not a food allergy or a digestive problem. Eating "forbidden" foods does not cause an immediate reaction. The phenylalanine from that food remains in the person's system, however, and as Phe accumulates over time they may experience concentration and mood problems, as well as eczema and other symptoms. For children, developmental problems may occur if levels are elevated frequently or remain elevated for a significant amount of time.

Optimal health ranges (or "target ranges") are between 120 and 360 µmol/L or equivalently 2 to 6 mg/dL, and aimed to be achieved during at least the first 10 years,^[31] to allow the brain to develop normally.

In the past, PKU-affected people were allowed to go off diet after approximately eight, then 18 years of age. Today, most physicians recommend PKU patients must manage their Phe levels throughout life. For teens and adults, somewhat higher levels of Phe may be tolerable, but restriction is still advised to prevent mood disorders and difficulty concentrating, among other neurological problems.^[32]

The diet requires severely restricting or eliminating foods high in Phe, such as soybeans, seal meat, eggwhites, shrimps, chicken breast, spirulina, watercrass, fish, whale, nuts, crayfish, lobster, tuna, turkey, legumes, elk meat and lowfat cottage cheese. ^[33] Starchy foods, such as potatoes and corn are generally acceptable in controlled amounts, but the quantity of Phe consumed from these foods must be monitored. A food diary is usually kept to record the amount of Phe consumed with each meal, snack, or drink. An "exchange" system can be used to calculate the amount of Phe in a food from the protein content identified on a nutritional information label. Lower-protein "medical food" substitutes are often used in place of normal bread, pasta, and other grain-based foods, which contain a significant amount of Phe. Many fruits and vegetables are lower in Phe and can be eaten in larger quantities. Infants may still be breastfed to provide all of the benefits of breastmilk, but the quantity must also be monitored and supplementation for missing nutrients will be required. The sweetener aspartame, present in many diet foods and soft drinks, must also be avoided, as aspartame contains phenylalanine.

Different patients can tolerate different amounts of Phe in their diet. Regular blood tests are required to determine the effects of dietary Phe intake on blood Phe level. Patients typically work with a professional dietitian to find a diet that meets their nutritional needs without causing their blood Phe level to exceed the target range.

Supplementary "protein substitute" formulas are typically prescribed for Classical PKU patients (starting in infancy) to provide the amino acids and other necessary nutrients that would otherwise be lacking in a low-phenylalanine diet. Tyrosine, which is normally derived from phenylalanine and which is necessary for normal brain function, is usually supplemented. Consumption of the protein substitute formulas can actually reduce phenylalanine levels, probably because it stops the process of protein catabolism from releasing Phe stored in the muscles and other tissues into the blood. Many PKU patients have their highest Phe levels after a period of fasting (such as overnight), because fasting triggers catabolism.^[34] A diet that is low in phenylalanine but does not include protein substitutes may also fail to lower blood Phe levels, since a nutritionally insufficient diet may also trigger catabolism. For all these reasons, the prescription formula is an important part of the treatment for patients with classic PKU.

The oral administration of tetrahydrobiopterin (or BH4) (a cofactor for the oxidation of phenylalanine) can reduce blood levels of this amino acid in certain patients.^[35]^[36] The company BioMarin Pharmaceutical has produced a tablet preparation of the compound sapropterin dihydrochloride (Kuvan), which is a form of tetrahydrobiopterin. Kuvan is the first drug that can help BH4-responsive PKU patients (defined among clinicians as about 1/2 of the PKU population) lower Phe levels to recommended ranges.^[37] Working closely with a dietitian, some PKU patients who respond to Kuvan may also be able to increase the amount of natural protein they can eat.^[38] After extensive clinical trials, Kuvan has been approved by the FDA for use in PKU therapy. Some researchers and clinicians working with PKU are finding Kuvan a safe and effective addition to dietary treatment and beneficial to patients with PKU.^[39]^[40]

Biomarin is currently conducting clinical trials to investigate another type of treatment for PKU. PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase or ‘PAL’) is an enzyme substitution therapy in which the missing PAH enzyme is replaced with an analogous enzyme that also breaks down Phe. PEG-PAL is now in Phase 2 clinical development to treat patients who do not adequately respond to KUVAN.^[41]

Dietary supplementation with large neutral amino acids(LNAAs), with or without the traditional PKU diet is another treatment strategy. The LNAAs (e.g. leu, tyr, trp, met, his, ile, val, thr) compete with phe for specific carrier proteins that transport LNAAs across the intestinal mucosa into the blood and across the blood brain barrier into the brain .

Studies^[42]^[43]^[44] have demonstrated that PKU patients given daily supplements of LNAAs have decreased plasma phe levels and reduced brain phe concentrations measured by magnetic resonance spectroscopy.^[45]

Another interesting treatment strategy for PKU patients is casein glycomacropeptide (CGMP), which is a milk peptide naturally free of Phe in its pure form^[46] CGMP can substitute the main part of the free amino acids in the PKU diet and provides several beneficial nutritional effects compared to free amino acids. The fact that CGMP is a peptide ensures that that the absorption rate of its amino acids is prolonged compared to free amino acids and thereby results in improved protein retention^[47] and increased satiety^[48] compared to free amino acids. Another important benefit of CGMP is that the taste is significantly improved^[47] when CGMP substitutes part of the free amino acids and this may help ensure improved compliance to the PKU diet.

Furthermore, CGMP contains a high amount of the phe lowering LNAAs, which constitutes about 41 g per 100 g protein^[46] and will therefore help maintain plasma phe levels in the target range.

Other therapies are currently under investigation, including gene therapy.

Maternal phenylketonuria

For women with phenylketonuria, it is essential for the health of their children to maintain low Phe levels before and during pregnancy.^[49] Though the developing fetus may only be a carrier of the PKU gene, the intrauterine environment can have very high levels of phenylalanine, which can cross the placenta. The child may develop congenital heart disease, growth retardation, microcephaly and intellectual disability as a result.^[50] PKU-affected women themselves are not at risk of additional complications during pregnancy.

In most countries, women with PKU who wish to have children are advised to lower their blood Phe levels (typically to between 2 and 6 mg/dL) before they become pregnant, and carefully control their levels throughout the pregnancy. This is achieved by performing regular blood tests and adhering very strictly to a diet, in general monitored on a day-to-day basis by a specialist metabolic dietitian. In many cases, as the fetus' liver begins to develop and produce PAH normally, the mother's blood Phe levels will drop, requiring an increased intake to remain within the safe range of 2–6 mg/dL. The mother's daily Phe intake may double or even triple by the end of the pregnancy, as a result. When maternal blood Phe levels fall below 2 mg/dL, anecdotal reports indicate that the mothers may suffer adverse effects, including headaches, nausea, hair loss, and general malaise. When low phenylalanine levels are maintained for the duration of pregnancy, there are no elevated levels of risk of birth defects compared with a baby born to a non-PKU mother.^[51]

Incidence

The mean incidence of PKU varies widely in different human populations. United States Caucasians are affected at a rate of 1 in 10,000.^[52] Turkey has the highest documented rate in the world, with 1 in 2,600 births, while countries such as Finland and Japan have extremely low rates with fewer than one case of PKU in 100,000 births. A 1987 study from Slovakia reports a Roma population with an extremely high incidence of PKU (one case in 40 births) due to extensive inbreeding.^[53] It is the most common amino acid metabolic problem in the United Kingdom.^{[citation needed]}

Country	Incidence of PKU
Australia	1 in 10,000^[54]
Canada	1 in 22,000^[54]
China	1 in 17,000^[54]
Czechoslovakia	1 in 7,000^[54]
Denmark	1 in 12,000^[54]
Finland	1 in 200,000^[54]
France	1 in 13,500^[54]
India	1 in 18,300
Ireland	1 in 4,500^[55]
Italy	1 in 17,000^[54]
Japan	1 in 125,000^[54]
Korea	1 in 41,000^[56]
Norway	1 in 14,500^[54]
Turkey	1 in 2,600^[54]
Philippines	1 in 102,000^[57]
Scotland	1 in 5,300^[54]
United Kingdom	1 in 14,300^[54]
United States	1 in 15,000^[58]

References

^ "Phenylketonuria: A-to-Z Guide from Diagnosis to Treatment to Prevention". DrGreene.com.
^ Filiano JJ (31 May 2006). "Neurometabolic Diseases in the Newborn". Clinics in Perinatology 33 (2): 411–479. doi:10.1016/j.clp.2006.03.013. PMID 16765732.
^ Macleod EL, Ney DM (1 January 2010). "Nutritional Management of Phenylketonuria". Annales Nestlé (English ed.) 68 (2): 58–69. doi:10.1159/000312813. PMC 2901905. PMID 22475869.
^ "NIH Consensus Statement". nih.gov.
^ James, William D.; Berger, Timothy G. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
^ ^a ^b Gonzalez, Jason; Willis, Monte S. (Feb 2010). "Ivar Asbjorn Folling Discovered Phenylketonuria (PKU)". Lab medicine 41 (2): 118–119. doi:10.1309/LM62LVV5OSLUJOQF.
^ "The heterozygote advantage in phenylketonuria.". PubMed Central (PMC).
^ Lewis, Ricki (1997). Human Genetics. Chicago, IL: Wm. C. Brown. pp. 247–248. ISBN 0-697-24030-4.
^ Oh HJ, Park ES, Kang S, Jo I, Jung SC (2004). "Long-Term Enzymatic and Phenotypic Correction in the Phenylketonuria Mouse Model by Adeno-Associated Virus Vector-Mediated Gene Transfer". Pediatric Research 56 (2): 278–284. doi:10.1203/01.PDR.0000132837.29067.0E. PMID 15181195.
^ Gibbs RA, Rogers J, Katze MG, Bumgarner R, Weinstock GM, Mardis ER, Remington KA, Strausberg RL, Venter JC et al. (April 2007). "Evolutionary and Biomedical Insights from the Rhesus Macaque Genome". Science 316 (5822): 222–234. doi:10.1126/science.1139247. PMID 17431167.
^ "The child who never grew". PubMed Central (PMC).
^ "NPKUA > Education > About PKU". npkua.org.
^ Fölling, Asbjörn (1 January 1934). "Über Ausscheidung von Phenylbrenztraubensäure in den Harn als Stoffwechselanomalie in Verbindung mit Imbezillität.". Hoppe-Seyler´s Zeitschrift für physiologische Chemie 227 (1–4): 169–181. doi:10.1515/bchm2.1934.227.1-4.169.
^ Centerwall SA, Centerwall WR (2000). "The discovery of phenylketonuria: the story of a young couple, two affected children, and a scientist". Pediatrics 105 (1 Pt 1): 89–103. doi:10.1542/peds.105.1.89. PMID 10617710.
^ Mitchell JJ, Trakadis YJ, Scriver CR (2011). "Phenylalanine hydroxylase deficiency". Genetics in medicine : official journal of the American College of Medical Genetics 13 (8): 697–707. doi:10.1097/GIM.0b013e3182141b48. PMID 21555948.
^ Kasper DC, Ratschmann R, Metz TF, Mechtler TP, Möslinger D, Konstantopoulou V, Item CB, Pollak A, Herkner KR (2010). "The National Austrian Newborn Screening Program – Eight years experience with mass spectrometry. Past, present, and future goals". Wiener klinische Wochenschrift 122 (21–22): 607–613. doi:10.1007/s00508-010-1457-3. PMID 20938748.
^ Komrower GM, Sardharwalla IB, Fowler B, Bridge C (1979). "The Manchester regional screening programme: A 10-year exercise in patient and family care". British medical journal 2 (6191): 635–638. doi:10.1136/bmj.2.6191.635. PMC 1596331. PMID 497752.
^ Mayo Clinic Staff (2007-12-20). "Phenylketonuria (PKU)". Mayo Clinic. Retrieved 2008-03-13.
^ Sarafoglou, Kyriakie; Hoffmann, Georg F.; Roth, Karl S. (eds.). Pediatric Endocrinology and Inborn Errors of Metabolism. New York: McGraw Hill Medical. p. 26.
^ "NPKUA > Resources > Recent Diagnosis". npkua.org.
^ "Videographer with Rare Disease Turns the Lens on Himself". everydayhealth.com.
^ "Phenylketonuria". Healthline. 20 August 2012.
^ http://www.genenames.org Phenylalanine hydroxylase (PAH) gene summary, retrieved September 8, 2006
^ Pietz J, Kreis R, Rupp A, Mayatepek E, Rating D, Boesch C, Bremer HJ (1999). "Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria". Journal of Clinical Investigation 103 (8): 1169–1178. doi:10.1172/JCI5017. PMC 408272. PMID 10207169.
^ Enns GM, Koch R, Brumm V, Blakely E, Suter R, Jurecki E (1 October 2010). "Suboptimal outcomes in patients with PKU treated early with diet alone: Revisiting the evidence". Molecular Genetics and Metabolism 101 (2–3): 99–109. doi:10.1016/j.ymgme.2010.05.017. PMID 20678948.
^ "Neurowiki2012 - Phenylketonuria". wikispaces.com.
^ Adler-Abramovich L, Vaks L, Carny O, Trudler D, Magno A, Caflisch A, Frenkel D, Gazit E (2012). "Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria". Nature Chemical Biology 8 (8): :701–706. doi:10.1038/nchembio.1002. PMID 22706200.
^ Surtees R, Blau N (2000). "The neurochemistry of phenylketonuria". European Journal of Pediatrics 169: S109–S113. doi:10.1007/PL00014370. PMID 11043156.
^ Online 'Mendelian Inheritance in Man' (OMIM) 261640
^ Michals K, Matalon R (1985). "Phenylalanine metabolites, attention span and hyperactivity". American Journal of Clinical Nutrition 42 (2): 361–5. PMID 4025205.
^ Chapter 55, page 255 in:Behrman, Richard E.; Kliegman, Robert; Nelson, Waldo E.; Karen Marcdante; Jenson, Hal B. (2006). Nelson essentials of pediatrics. Elsevier/Saunders. ISBN 1-4160-0159-X.
^ "National PKU News: Adults". pkunews.org.
^ "Foods highest in Phenylalanine". self.com.
^ MacDonald A, Rylance GW, Asplin D, Hall SK, Booth IW (1998). "Does a single plasma phenylalanine predict quality of control in phenylketonuria?". Archives of disease in childhood 78 (2): 122–6. doi:10.1136/adc.78.2.122. PMC 1717471. PMID 9579152.
^ Burton, BK; Kar S; Kirkpatrick P (2008). "Fresh from the Pipeline: Sapropterin". Nature Reviews Drug Discovery 7 (3): 199–200. doi:10.1038/nrd2540.
^ Michals-Matalon K (2008). "Sapropterin dihydrochloride, 6-R-L-erythro-5,6,7,8-tetrahydrobiopterin, in the treatment of phenylketonuria". Expert Opin Investig Drugs 17 (2): 245–251. doi:10.1517/13543784.17.2.245. PMID 18230057.
^ Burton BK, Grange DK, Milanowski A, Vockley G, Feillet F, Crombez EA, Abadie V, Harding CO, Cederbaum S, Dobbelaere D, Smith A, Dorenbaum A (2007). "The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study". Journal of Inherited Metabolic Disorders 30 (5): 700–707. doi:10.1007/s10545-007-0605-z. PMID 17846916.
^ Levy H, Burton B, Cederbaum S, Scriver C (2007). "Recommendations for evaluation of responsiveness to tetrahydrobiopterin (BH(4)) in phenylketonuria and its use in treatment". Mol Genet Metab 92 (4): 287–291. doi:10.1016/j.ymgme.2007.09.017. PMID 18036498.
^ Levy HL, Milanowski A, Chakrapani A, Cleary M, Lee P, Trefz FK, Whitley CB, Feillet F, Feigenbaum AS, Bebchuk JD, Christ-Schmidt H, Dorenbaum A (2007). "Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study". Lancet 370 (9586): 504–510. doi:10.1016/S0140-6736(07)61234-3. PMID 17693179.
^ Lee P, Treacy EP, Crombez E, Wasserstein M, Waber L, Wolff J, Wendel U, Dorenbaum A, Bebchuk J, Christ-Schmidt H, Seashore M, Giovannini M, Burton BK, Morris AA (2008). "Safety and efficacy of 22 weeks of treatment with sapropterin dihydrochloride in patients with phenylketonuria". American Journal of Medical Genetics 146A (22): 2851–2859. doi:10.1002/ajmg.a.32562. PMID 18932221.
^ "BioMarin : Pipeline : Pipeline Overview : BMN 165 for PKU". bmrn.com.
^ Matalon R, Michals-Matalon K, Bhatia G, Burlina AB, Burlina AP, Braga C, Fiori L, Giovannini M, Grechanina E, Novikov P, Grady J, Tyring SK, Guttler F (Apr 2007). "Double blind placebo control trial of large neutral amino acids in treatment of PKU: effect on blood phenylalanine.". Journal of Inherited Metabolic Disease 30 (2): 153–8. doi:10.1007/s10545-007-0556-4. PMID 17334706.
^ Schindeler S, Ghosh-Jerath S, Thompson S, Rocca A, Joy P, Kemp A, Rae C, Green K, Wilcken B, Christodoulou J (May 2007). "The effects of large neutral amino acid supplements in PKU: an MRS and neuropsychological study.". Molecular genetics and metabolism 91 (1): 48–54. doi:10.1016/j.ymgme.2007.02.002. PMID 17368065.
^ Sanjurjo P, Aldamiz L, Georgi G, Jelinek J, Ruiz JI, Boehm G (Jan 2003). "Dietary threonine reduces plasma phenylalanine levels in patients with hyperphenylalaninemia.". Journal of pediatric gastroenterology and nutrition 36 (1): 23–6. doi:10.1097/00005176-200301000-00007. PMID 12499992.
^ Moats RA, Moseley KD, Koch R, Nelson M (Dec 2003). "Brain phenylalanine concentrations in phenylketonuria: research and treatment of adults.". Pediatrics 112 (6 Pt 2): 1575–9. PMID 14654668.
^ ^a ^b Etzel MR (Apr 2004). "Manufacture and use of dairy protein fractions.". The Journal of nutrition 134 (4): 996S–1002S. PMID 15051860.
^ ^a ^b van Calcar SC, MacLeod EL, Gleason ST, Etzel MR, Clayton MK, Wolff JA, Ney DM (Apr 2009). "Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids.". The American journal of clinical nutrition 89 (4): 1068–77. doi:10.3945/ajcn.2008.27280. PMC 2667457. PMID 19244369.
^ MacLeod EL, Clayton MK, van Calcar SC, Ney DM (Aug 2010). "Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketonuria.". Molecular genetics and metabolism 100 (4): 303–8. doi:10.1016/j.ymgme.2010.04.003. PMC 2906609. PMID 20466571.
^ Lee PJ, Ridout D, Walter JH, Cockburn F (2005). "Maternal phenylketonuria: report from the United Kingdom Registry 1978–97". Archives of Disease in Childhood 90 (2): 143–146. doi:10.1136/adc.2003.037762. PMC 1720245. PMID 15665165.
^ Rouse B, Azen C, Koch R, Matalon R, Hanley W, de la Cruz F, Trefz F, Friedman E, Shifrin H (1997). "Maternal phenylketonuria collaborative study (MPKUCS) offspring: Facial anomalies, malformations, and early neurological sequelae". American Journal of Medical Genetics 69 (1): 89–95. doi:10.1002/(SICI)1096-8628(19970303)69:1<89::AID-AJMG17>3.0.CO;2-K. PMID 9066890.
^ lsuhsc.edu Genetics and Louisiana Families
^ Bickel, H.;, Bachmann, C.; Beckers, R.; Brandt, N.J.; Clayton, B.E.; Corrado, G; et al. (1981). "Neonatal mass screening for metabolic disorders: summary of recent sessions of the committee of experts to study inborn metabolic diseases". public health committee, Eur. J. Pediatr. (137): 133–139. doi:10.1007/BF00441305.
^ Ferák V, Siváková D, Sieglová Z (1987). "Slovenskí Cigáni (Rómovia) – populácia s najvyšším koeficientom inbrídingu v Európe.". Bratislavské lekárske listy (Bratislava Medical Journal) 87 (2): 168–175.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m Williams RA, Mamotte CD, Burnett JR (2008). "Phenylketonuria: an inborn error of phenylalanine metabolism.". Clin Biochem Rev 29 (1): 31–41. PMC 2423317. PMID 18566668.
^ DiLella AG, Kwok SC, Ledley FD, Marvit J, Woo SL (1986). "Molecular structure and polymorphic map of the human phenylalanine hydroxylase gene". Biochemistry 25 (4): 743–749. doi:10.1021/bi00352a001. PMID 3008810.
^ Lee DH, Koo SK, Lee KS, Yeon YJ, Oh HJ, Kim SW, Lee SJ, Kim SS, Lee JE, Jo I, Jung SC (2004). "The molecular basis of phenylketonuria in Koreans". Journal of Human Genetics 49 (1): 617–621. doi:10.1007/s10038-004-0197-5. PMID 15503242.
^ "Philippine Society for Orphan Disorders – Current Registry". psod.org.ph.
^ "Medscape: Medscape Access". Emedicine.medscape.com. Retrieved 2013-01-26.

External links

Phenylketonuria at DMOZ
Canadian PKU and Allied Disorders
GeneReviews/NCBI/NIH/UW entry on Phenylalanine Hydroxylase Deficiency
National Society for Phenylketonuria
National PKU News
Videos, Blogs, PKU Community
Online PKU Community
Phenylalanine Hydroxylase Locus Knowledgebase
National PKU Alliance

UpToDate Contents

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1. フェニルケトン尿症の概要 overview of phenylketonuria
2. 妊娠前の外来診察 the preconception office visit
3. 先天性奇形に対するアプローチ approach to congenital malformations
4. 先天異常の原則 principles of teratology
5. 胎児心奇形：スクリーニング、評価、および母体のマネージメント fetal cardiac abnormalities screening evaluation and pregnancy management

English Journal

Co-administration of Creatine Plus Pyruvate Prevents the Effects of Phenylalanine Administration to Female Rats During Pregnancy and Lactation on Enzymes Activity of Energy Metabolism in Cerebral Cortex and Hippocampus of the Offspring.

Bortoluzzi VT1, de Franceschi ID, Rieger E, Wannmacher CM.
Neurochemical research.Neurochem Res.2014 Aug;39(8):1594-602. doi: 10.1007/s11064-014-1353-8. Epub 2014 Jun 11.
Phenylketonuria (PKU) is the most frequent inborn error of metabolism. It is caused by deficiency in the activity of phenylalanine hydroxylase, leading to accumulation of phenylalanine and its metabolites. Untreated maternal PKU or hyperphenylalaninemia may result in nonphenylketonuric offspring wit
PMID 24916961

A new case of maternal phenylketonuria treated with sapropterin dihydrochloride (6R-BH4).

Aldámiz-Echevarría L1, Couce ML, Llarena M, Andrade F.
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.Gynecol Endocrinol.2014 Jun 13:1-3. [Epub ahead of print]
Abstract Purpose: A woman with phenylketonuria (PKU) was diagnosed through neonatal screening, her PAH mutation was p.V388M/p.I65T, for which she received treatment with phenylalanine restriction, and was administered oral sapropterin dihydrochloride (6R-BH4) from the age of thirty. The purpose of t
PMID 24927077

Phenylketonuria Scientific Review Conference: state of the science and future research needs.

Camp KM1, Parisi MA2, Acosta PB3, Berry GT4, Bilder DA5, Blau N6, Bodamer OA7, Brosco JP8, Brown CS9, Burlina AB10, Burton BK11, Chang CS12, Coates PM13, Cunningham AC14, Dobrowolski SF15, Ferguson JH16, Franklin TD17, Frazier DM18, Grange DK19, Greene CL20, Groft SC21, Harding CO22, Howell RR23, Huntington KL24, Hyatt-Knorr HD25, Jevaji IP26, Levy HL27, Lichter-Konecki U28, Lindegren ML29, Lloyd-Puryear MA30, Matalon K31, MacDonald A32, McPheeters ML33, Mitchell JJ34, Mofidi S35, Moseley KD36, Mueller CM37, Mulberg AE38, Nerurkar LS39, Ogata BN40, Pariser AR41, Prasad S42, Pridjian G43, Rasmussen SA44, Reddy UM45, Rohr FJ46, Singh RH47, Sirrs SM48, Stremer SE49, Tagle DA50, Thompson SM51, Urv TK52, Utz JR53, van Spronsen F54, Vockley J55, Waisbren SE56, Weglicki LS57, White DA58, Whitley CB59, Wilfond BS60, Yannicelli S61, Young JM62.
Molecular genetics and metabolism.Mol Genet Metab.2014 Jun;112(2):87-122. doi: 10.1016/j.ymgme.2014.02.013. Epub 2014 Mar 6.
New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, part
PMID 24667081

Japanese Journal

新生児マス・スクリーニングで発見されたフェニルケトン尿症の長期追跡の意義

青木菊麿,大和田操,北川照男
日本マス・スクリーニング学会誌 = Journal of Japanese Society for Mass-screening 17(1), 11-17, 2007-06-01
NAID 10019820519

マターナルPKUの栄養管理に関する研究

大和田操,佐藤陽子,小沼敏二
日本マス・スクリーニング学会誌 = Journal of Japanese Society for Mass-screening 8(2), 33, 1998-08-27
NAID 10020472589

Related Pictures

★リンクテーブル★

リンク元	「母性フェニルケトン尿症」「maternal PKU」
関連記事	「maternal」「phenylketonuria」

「母性フェニルケトン尿症」

Phenylketonuria
	Phenylalanine
Classification and external resources
ICD-10	E70.0
ICD-9	270.1
OMIM	261600 261630
DiseasesDB	9987
MedlinePlus	001166
eMedicine	ped/1787 derm/712 article/947781
Patient UK	Phenylketonuria
MeSH	D010661

　　[★]

英: maternal phenylketonuria、maternal PKU
同: マターナルPKU、母体フェニルケトン尿症
関: フェニルケトン尿症

[show details]

母性フェニルケトン尿症 : 46 件
母体フェニルケトン尿症 : 2 件

「maternal PKU」

　　[★]

母性フェニルケトン尿症

関: maternal phenylketonuria

「maternal」

　　[★]

adj.

母系性の、母系的な、母性の、母性的な、母体の

関: maternally、maternity、motherhood

「phenylketonuria」

　　[★] フェニルケトン尿症 PKU 　

[1] "Phenylketonuria: A-to-Z Guide from Diagnosis to Treatment to Prevention". DrGreene.com.

[pmid16765732-2] Filiano JJ (31 May 2006). "Neurometabolic Diseases in the Newborn". Clinics in Perinatology 33 (2): 411–479. doi:10.1016/j.clp.2006.03.013. PMID 16765732.

[pmid22475869-3] Macleod EL, Ney DM (1 January 2010). "Nutritional Management of Phenylketonuria". Annales Nestlé (English ed.) 68 (2): 58–69. doi:10.1159/000312813. PMC 2901905. PMID 22475869.

[NIH_concensus_PKU2000-4] "NIH Consensus Statement". nih.gov.

[Andrews-5] James, William D.; Berger, Timothy G. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.

[Gonzalez.2C_Jason.3B_Willis.2C_Monte_S._118.E2.80.93119-6] Gonzalez, Jason; Willis, Monte S. (Feb 2010). "Ivar Asbjorn Folling Discovered Phenylketonuria (PKU)". Lab medicine 41 (2): 118–119. doi:10.1309/LM62LVV5OSLUJOQF.

[7] "The heterozygote advantage in phenylketonuria.". PubMed Central (PMC).

[Lewis1997-8] Lewis, Ricki (1997). Human Genetics. Chicago, IL: Wm. C. Brown. pp. 247–248. ISBN 0-697-24030-4.

[9] Oh HJ, Park ES, Kang S, Jo I, Jung SC (2004). "Long-Term Enzymatic and Phenotypic Correction in the Phenylketonuria Mouse Model by Adeno-Associated Virus Vector-Mediated Gene Transfer". Pediatric Research 56 (2): 278–284. doi:10.1203/01.PDR.0000132837.29067.0E. PMID 15181195.

[10] Gibbs RA, Rogers J, Katze MG, Bumgarner R, Weinstock GM, Mardis ER, Remington KA, Strausberg RL, Venter JC et al. (April 2007). "Evolutionary and Biomedical Insights from the Rhesus Macaque Genome". Science 316 (5822): 222–234. doi:10.1126/science.1139247. PMID 17431167.

[11] "The child who never grew". PubMed Central (PMC).

[12] "NPKUA > Education > About PKU". npkua.org.

[Folling-13] Fölling, Asbjörn (1 January 1934). "Über Ausscheidung von Phenylbrenztraubensäure in den Harn als Stoffwechselanomalie in Verbindung mit Imbezillität.". Hoppe-Seyler´s Zeitschrift für physiologische Chemie 227 (1–4): 169–181. doi:10.1515/bchm2.1934.227.1-4.169.

[14] Centerwall SA, Centerwall WR (2000). "The discovery of phenylketonuria: the story of a young couple, two affected children, and a scientist". Pediatrics 105 (1 Pt 1): 89–103. doi:10.1542/peds.105.1.89. PMID 10617710.

[pkureview-15] Mitchell JJ, Trakadis YJ, Scriver CR (2011). "Phenylalanine hydroxylase deficiency". Genetics in medicine : official journal of the American College of Medical Genetics 13 (8): 697–707. doi:10.1097/GIM.0b013e3182141b48. PMID 21555948.

[austriascreening-16] Kasper DC, Ratschmann R, Metz TF, Mechtler TP, Möslinger D, Konstantopoulou V, Item CB, Pollak A, Herkner KR (2010). "The National Austrian Newborn Screening Program – Eight years experience with mass spectrometry. Past, present, and future goals". Wiener klinische Wochenschrift 122 (21–22): 607–613. doi:10.1007/s00508-010-1457-3. PMID 20938748.

[englandscreening-17] Komrower GM, Sardharwalla IB, Fowler B, Bridge C (1979). "The Manchester regional screening programme: A 10-year exercise in patient and family care". British medical journal 2 (6191): 635–638. doi:10.1136/bmj.2.6191.635. PMC 1596331. PMID 497752.

[18] Mayo Clinic Staff (2007-12-20). "Phenylketonuria (PKU)". Mayo Clinic. Retrieved 2008-03-13.

[sarafaglou-19] Sarafoglou, Kyriakie; Hoffmann, Georg F.; Roth, Karl S. (eds.). Pediatric Endocrinology and Inborn Errors of Metabolism. New York: McGraw Hill Medical. p. 26.

[20] "NPKUA > Resources > Recent Diagnosis". npkua.org.

[21] "Videographer with Rare Disease Turns the Lens on Himself". everydayhealth.com.

[22] "Phenylketonuria". Healthline. 20 August 2012.

[23] ttp://www.genenames.org Phenylalanine hydroxylase (PAH) gene summary, retrieved September 8, 2006

[Pietz-24] Pietz J, Kreis R, Rupp A, Mayatepek E, Rating D, Boesch C, Bremer HJ (1999). "Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria". Journal of Clinical Investigation 103 (8): 1169–1178. doi:10.1172/JCI5017. PMC 408272. PMID 10207169.

[pmid20678948-25] Enns GM, Koch R, Brumm V, Blakely E, Suter R, Jurecki E (1 October 2010). "Suboptimal outcomes in patients with PKU treated early with diet alone: Revisiting the evidence". Molecular Genetics and Metabolism 101 (2–3): 99–109. doi:10.1016/j.ymgme.2010.05.017. PMID 20678948.

[26] "Neurowiki2012 - Phenylketonuria". wikispaces.com.

[27] Adler-Abramovich L, Vaks L, Carny O, Trudler D, Magno A, Caflisch A, Frenkel D, Gazit E (2012). "Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria". Nature Chemical Biology 8 (8): :701–706. doi:10.1038/nchembio.1002. PMID 22706200.

[28] Surtees R, Blau N (2000). "The neurochemistry of phenylketonuria". European Journal of Pediatrics 169: S109–S113. doi:10.1007/PL00014370. PMID 11043156.

[29] Online 'Mendelian Inheritance in Man' (OMIM) 261640

[30] Michals K, Matalon R (1985). "Phenylalanine metabolites, attention span and hyperactivity". American Journal of Clinical Nutrition 42 (2): 361–5. PMID 4025205.

[31] Chapter 55, page 255 in:Behrman, Richard E.; Kliegman, Robert; Nelson, Waldo E.; Karen Marcdante; Jenson, Hal B. (2006). Nelson essentials of pediatrics. Elsevier/Saunders. ISBN 1-4160-0159-X.

[32] "National PKU News: Adults". pkunews.org.

[33] "Foods highest in Phenylalanine". self.com.

[34] MacDonald A, Rylance GW, Asplin D, Hall SK, Booth IW (1998). "Does a single plasma phenylalanine predict quality of control in phenylketonuria?". Archives of disease in childhood 78 (2): 122–6. doi:10.1136/adc.78.2.122. PMC 1717471. PMID 9579152.

[35] Burton, BK; Kar S; Kirkpatrick P (2008). "Fresh from the Pipeline: Sapropterin". Nature Reviews Drug Discovery 7 (3): 199–200. doi:10.1038/nrd2540.

[pmid18230057-36] Michals-Matalon K (2008). "Sapropterin dihydrochloride, 6-R-L-erythro-5,6,7,8-tetrahydrobiopterin, in the treatment of phenylketonuria". Expert Opin Investig Drugs 17 (2): 245–251. doi:10.1517/13543784.17.2.245. PMID 18230057.

[37] Burton BK, Grange DK, Milanowski A, Vockley G, Feillet F, Crombez EA, Abadie V, Harding CO, Cederbaum S, Dobbelaere D, Smith A, Dorenbaum A (2007). "The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study". Journal of Inherited Metabolic Disorders 30 (5): 700–707. doi:10.1007/s10545-007-0605-z. PMID 17846916.

[38] Levy H, Burton B, Cederbaum S, Scriver C (2007). "Recommendations for evaluation of responsiveness to tetrahydrobiopterin (BH(4)) in phenylketonuria and its use in treatment". Mol Genet Metab 92 (4): 287–291. doi:10.1016/j.ymgme.2007.09.017. PMID 18036498.

[39] Levy HL, Milanowski A, Chakrapani A, Cleary M, Lee P, Trefz FK, Whitley CB, Feillet F, Feigenbaum AS, Bebchuk JD, Christ-Schmidt H, Dorenbaum A (2007). "Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study". Lancet 370 (9586): 504–510. doi:10.1016/S0140-6736(07)61234-3. PMID 17693179.

[40] Lee P, Treacy EP, Crombez E, Wasserstein M, Waber L, Wolff J, Wendel U, Dorenbaum A, Bebchuk J, Christ-Schmidt H, Seashore M, Giovannini M, Burton BK, Morris AA (2008). "Safety and efficacy of 22 weeks of treatment with sapropterin dihydrochloride in patients with phenylketonuria". American Journal of Medical Genetics 146A (22): 2851–2859. doi:10.1002/ajmg.a.32562. PMID 18932221.

[41] "BioMarin : Pipeline : Pipeline Overview : BMN 165 for PKU". bmrn.com.

[pmid17334706-42] Matalon R, Michals-Matalon K, Bhatia G, Burlina AB, Burlina AP, Braga C, Fiori L, Giovannini M, Grechanina E, Novikov P, Grady J, Tyring SK, Guttler F (Apr 2007). "Double blind placebo control trial of large neutral amino acids in treatment of PKU: effect on blood phenylalanine.". Journal of Inherited Metabolic Disease 30 (2): 153–8. doi:10.1007/s10545-007-0556-4. PMID 17334706.

[pmid17368065-43] Schindeler S, Ghosh-Jerath S, Thompson S, Rocca A, Joy P, Kemp A, Rae C, Green K, Wilcken B, Christodoulou J (May 2007). "The effects of large neutral amino acid supplements in PKU: an MRS and neuropsychological study.". Molecular genetics and metabolism 91 (1): 48–54. doi:10.1016/j.ymgme.2007.02.002. PMID 17368065.

[pmid12499992-44] Sanjurjo P, Aldamiz L, Georgi G, Jelinek J, Ruiz JI, Boehm G (Jan 2003). "Dietary threonine reduces plasma phenylalanine levels in patients with hyperphenylalaninemia.". Journal of pediatric gastroenterology and nutrition 36 (1): 23–6. doi:10.1097/00005176-200301000-00007. PMID 12499992.

[pmid14654668-45] Moats RA, Moseley KD, Koch R, Nelson M (Dec 2003). "Brain phenylalanine concentrations in phenylketonuria: research and treatment of adults.". Pediatrics 112 (6 Pt 2): 1575–9. PMID 14654668.

[pmid15051860-46] Etzel MR (Apr 2004). "Manufacture and use of dairy protein fractions.". The Journal of nutrition 134 (4): 996S–1002S. PMID 15051860.

[pmid19244369-47] van Calcar SC, MacLeod EL, Gleason ST, Etzel MR, Clayton MK, Wolff JA, Ney DM (Apr 2009). "Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids.". The American journal of clinical nutrition 89 (4): 1068–77. doi:10.3945/ajcn.2008.27280. PMC 2667457. PMID 19244369.

[pmid20466571-48] MacLeod EL, Clayton MK, van Calcar SC, Ney DM (Aug 2010). "Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketonuria.". Molecular genetics and metabolism 100 (4): 303–8. doi:10.1016/j.ymgme.2010.04.003. PMC 2906609. PMID 20466571.

[49] Lee PJ, Ridout D, Walter JH, Cockburn F (2005). "Maternal phenylketonuria: report from the United Kingdom Registry 1978–97". Archives of Disease in Childhood 90 (2): 143–146. doi:10.1136/adc.2003.037762. PMC 1720245. PMID 15665165.

[50] Rouse B, Azen C, Koch R, Matalon R, Hanley W, de la Cruz F, Trefz F, Friedman E, Shifrin H (1997). "Maternal phenylketonuria collaborative study (MPKUCS) offspring: Facial anomalies, malformations, and early neurological sequelae". American Journal of Medical Genetics 69 (1): 89–95. doi:10.1002/(SICI)1096-8628(19970303)69:1<89::AID-AJMG17>3.0.CO;2-K. PMID 9066890.

[web-51] suhsc.edu Genetics and Louisiana Families

[52] Bickel, H.;, Bachmann, C.; Beckers, R.; Brandt, N.J.; Clayton, B.E.; Corrado, G; et al. (1981). "Neonatal mass screening for metabolic disorders: summary of recent sessions of the committee of experts to study inborn metabolic diseases". public health committee, Eur. J. Pediatr. (137): 133–139. doi:10.1007/BF00441305.

[53] Ferák V, Siváková D, Sieglová Z (1987). "Slovenskí Cigáni (Rómovia) – populácia s najvyšším koeficientom inbrídingu v Európe.". Bratislavské lekárske listy (Bratislava Medical Journal) 87 (2): 168–175.

[pmid18566668-54] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m Williams RA, Mamotte CD, Burnett JR (2008). "Phenylketonuria: an inborn error of phenylalanine metabolism.". Clin Biochem Rev 29 (1): 31–41. PMC 2423317. PMID 18566668.

[55] DiLella AG, Kwok SC, Ledley FD, Marvit J, Woo SL (1986). "Molecular structure and polymorphic map of the human phenylalanine hydroxylase gene". Biochemistry 25 (4): 743–749. doi:10.1021/bi00352a001. PMID 3008810.

[56] Lee DH, Koo SK, Lee KS, Yeon YJ, Oh HJ, Kim SW, Lee SJ, Kim SS, Lee JE, Jo I, Jung SC (2004). "The molecular basis of phenylketonuria in Koreans". Journal of Human Genetics 49 (1): 617–621. doi:10.1007/s10038-004-0197-5. PMID 15503242.

[57] "Philippine Society for Orphan Disorders – Current Registry". psod.org.ph.

[medscape947781-58] "Medscape: Medscape Access". Emedicine.medscape.com. Retrieved 2013-01-26.

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maternal phenylketonuria