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Blood phenylalanine

Other causes of PKU secondary to defective tetrahydrobiopterin synthesis include GTP cyclohydrolase deficiency and 6-pyravoyltetrahydrobiopterin synthase deficiency. Patients with either defect have psychomotor retardation, truncal hypotonia with limb hypertonia, seizures and a tendency to hyperthermia. The intravenous administration of BH4 may lower blood phenylalanine levels but this cofactor may not readily cross the blood-brain barrier. Treatment with synthetic pterin analogs or supplementation with tryptophan and carbidopa may prove more efficacious, particularly if treatment is started early in life. [Pg.673]

Infants with classic phenylketonuria (PKU) are normal at birth but if untreated show slow development, severe mental retardation, autistic symptoms, and loss of motor control. Children may have pale skin and white-blonde hair. The neurotoxic effects relate to high levels of phenylalanine and not to the phenylketones from which the name of the disease derives. Infants are routinely screened a few days after birth for blood phenylalanine level. Treatment consists of a life-long semisynthetic diet restricted in phenylalanine (smalt quantities are necessary because it is an essential amino acid). Aspartame (N-aspartyl-phenylalanine methyl ester), which is widely used as an artificial sweetener, must be strictly avoided by phenyiketonurics. [Pg.248]

An unaffected patient will have a negative DNPH result. Mildly affected or partially treated patients may also yield negative results. Patients with a blood phenylalanine level (indicative of PKU) over 1 mmol/1 should generate positive DNPH results. Patients with a blood leucine level (indicative of MSUD) of 0.8 mmol/1 or higher usually show a positive DNPH result. Patients with pyruvate metabolic disorders may also give positive results, as will patients with true and transient disorders of tyrosine degradation. [Pg.31]

Treatment of PKU Most natural protein contains phenylalanine, and it is impossible to satisfy the body s protein requirement when ingesting a normal diet without exceeding the phenylalanine limit. Therefore, in PKU, blood phenylalanine is maintained in the normal range by feeding synthetic amino acid preparations low in phenylalanine, supplemented with some natural foods (such as... [Pg.269]

The concentration of phenylalanine in the blood of neonates is used to screen for phenylketonuria (PKU). Explain the biochemical basis for the correlation of elevated blood phenylalanine concentration and PKU. Explain why restriction of dietary phenylalanine is critically important for youngsters with PKU. [Pg.532]

A newborn child was found to be lethargic and jaundiced and, at 6 days of age, showed elevated blood phenylalanine levels. He was placed on a low-phenyla-... [Pg.578]

Provide a diagnosis for this patient, and explain all the chemical data provided on the basis of your diagnosis. How would you treat this patient What scientific conclusion can you make regarding the normal relationship between blood phenylalanine and "biopterin" levels ... [Pg.580]

Individuals with the rare, genetic disease PKU cannot properly metabolize phenylalanine. These individuals are placed on special low-phenylalanine diets to control their blood phenylalanine concentrations, and need to be aware that aspartame is a source of phenylalanine. [Pg.185]

Phenylalanine ammonia lyase Yeast Converts phenylanine to trans-aammac acid and ammonia reduction of blood phenylalanine in phenylketonurics Sarkissian et al. (1999) and Ikeda et al. (2005)... [Pg.30]

Until the 1980s, most clinics in North America and Europe recommended diet discontinuation during middle childhood (Schuett and Brown, 1984). At about age 5 or 6 years, most children with PKU were suddenly allowed to eat as much protein (phenylalanine) as they desired. Even though it was known that their blood phenylalanine levels would rise, it was thought that their cognitive abilities would be unaffected. The fact that high phenylalanine levels are known to affect myelin in the brain, and that myelination is essentially complete after infancy, provided the rationale for this approach to treatment for PKU. Moreover, children who did not adhere to the diet despite medical recommendations did not become mentally retarded. Therefore, the policy of diet discontinuation was adopted. [Pg.401]

Many studies have focused on the blood phenylalanine level in treated PKU. Factors such as timing of treatment initiation, lifetime level of metabolic control, and current dietary status, all have an impact. In most studies, if treatment is initially delayed past the first 3 months of life, a child performs less well than siblings with PKU who are treated earlier. If metabolic control is variable throughout childhood, the individual tends to have poorer mental processing skills, slower reaction time, diminished achievement, and lower IQ scores. One study has documented IQ loss in early treated adolescents with elevated phenylalanine levels (Beasley et al., 1994). By 18 years of age, 27% have an IQ less than 70. IQ is significantly related to the average phenylalanine control between birth and 14 years of age. The current blood phenylalanine level in an individual with PKU is also correlated with reaction time (Clarke et al., 1987 Schmidt et al., 1994) and is... [Pg.402]

The possibility exists that neuropsychological performance in treated PKU is related to the extent of the enzyme block. Individuals with natural blood phenylalanine levels in the range of non-PKU mild hyperphenylalaninemia perform at a higher level than early treated individuals with mild PKU (also called atypical PKU ), who in turn attain higher scores than those with classic PKU therefore, the greater the activity of the phenylalanine hydroxylase enzyme, the better a person s functioning. [Pg.403]

Neuropsychological tests considered to be particularly sensitive to prefrontal cortical functioning - such as the tests of motor planning, visual search, and verbal fluency the Tower of Hanoi the Stroop Color World Test and the Wisconsin Card Sorting Test-havebeen used to test this hypothesis. Diamond etal. (1994) reported that early and continuously treated children (with blood phenylalanine levels... [Pg.403]

Researchers have also found evidence for impairment in visual contrast sensitivity, when blood phenylalanine levels are elevated. This is relevant as it is hypothesized that the retina is also highly sensitive to moderate reduction in brain dopamine (Stemerdink, 1996 Diamond, 1994 Guttler and Lou, 1986). [Pg.404]

Not all studies, however, support the dopamine-prefrontal dysfunction hypothesis. Mazzocco et al. (1994), using the Tower of Hanoi and visual search tests, found that children aged 6-13 who were treated early and continuously showed no deficits on the neuropsychological tests, despite a range of blood phenylalanine levels. [Pg.404]

A disease in which hypomyelination occurs in specific forebrain tracts, but neurons and their axons are spared, is the autosomal recessive disorder PKU (Malamud, 1996 Dyer et al., 1996). As already mentioned, PKU is caused by a rise in blood phenylalanine (Phe) levels, due to a deficiency in the enzyme phenylalanine hydroxylase (PHA) (Scriver et al., 1995), which is expressed primarily in liver and not in brain, and catalyzes the conversion of Phe to tyrosine (Lee et al. 2003a and Lee et al. 2005). Blood Phe levels normally are about 121 mmol however, in untreated individuals (and mice) with PKU, levels may increase to 1,200 p. or more. For the past several decades, newborns diagnosed with PKU are placed on a low Phe diet for life. The low Phe diet decreases Phe levels in blood and brain, thereby allowing myelination to proceed (Thompson et al., 1993 Pietz et al., 1995). Individuals with PKU that are continuously treated from birth avoid the severe mental retardation that occurs in untreated individuals (Levy et al., 1994). [Pg.405]

Phenylketonuria, an inborn error of phenylalanine metabolism, occurs with a frequency of about 1 in 10,000 births and is treated with a strict dietary regimen. Recently, some patients with PKU have been found to show increased tolerance towards phenylalanine intake, while receiving tetrahydrobiopterin (BH ) supplementation. We have treated two infants with BH -responsive PKU with BH for more than 2 years. No additional dietary control was required to maintain blood phenylalanine concentrations in the desired range. Both children have shown normal development. Generally, these results suggest that BH treatment might be an option for some patients with mild PKU, as it frees them from dietary restriction and thus improves their quality of life. [Pg.413]

Tolerance is usually stable by 2-5 years of age as phenylalanine requirements are based on a combination of size (increasing with age) and rate of growth (decreasing with age). For any individutil, phenylalanine intake is adjusted based on frequent blood phenylalanine monitoring... [Pg.68]

In inherited metabolic disorders, not only is total protein a major consideration, but also the balance of individual amino acids. Excessive or imbalanced plasma amino add concentrations negatively affect absorption, protein synthesis, and brain concentrations of indispensable amino acids. In PKU, high blood phenylalanine concentrations cause high phenylalanine concentrations on the brain [52, 53]. In organic acidemias and maple syrup urine disease, imbalances in several or more indispensable amino adds can significantly affect protein synthesis (Fig. 7.5) (Chap. 11). [Pg.68]

Classification of the severity of phenylketonuria is based on the type of the genetic mutations in phenylalanie hydroxylase (PAH) gene, dietary phenylalanine tolerance, and prelreatment blood phenylalanine concentrations. [Pg.89]

The etiology of brain damage in PKU has not been fully elucidated however, high blood phenylalanine concentrations are associated with changes in brain morphology (gray and white matter) and decreased neurotransmitter synthesis. [Pg.89]

Unseated, late-treated, or poorly controlled patients have chronically elevated blood phenylalanine concentrations that lead to progressive... [Pg.91]

Eighty years after the discovery of PKU, the pathogenesis of brain dysfunction and the exact mechanisms of phenylalanine neurotoxicity have yet to be elucidated. Although there is a common agreement about the relationship between blood phenylalanine concentration and cognitive outcome in PKU, the concentration of phenylalanine... [Pg.92]

High concentrations of blood phenylalanine result in increased uptake of phenylalanine into the brain and concomitant dcCTease in the uptake of other large neutral amino adds (LNAA). Phenylalanine is transported into the brain by one of the LNAA carriers, the 1. -amino add transporter 1 (LAT-1) [45 8]. This transporter also selectively transports the amino adds valine, isoleucine, methionine, threonine, tryptophan, tyrosine, and histidine. The binding of the LNAA to the LAT-1 transporter is a competitive process the rate of transport is proportionate to the blood concentration of all the transported amino acids [49]. This system has the highest affinity for phenylalanine, which in case of its high concentration in the blood, significantly decreases the transport of other LNAA and more phenylalanine is transported into the brain. By influence on the activity of tyrosine and tryptophan hydroxylases, elevated brain phenylalanine concentrations also negatively impact the synthesis of catecholamines and serotonin in the brain due to the altered metabolism of tyrosine and tryptophan [4]. [Pg.93]

Phenylalanine and related metabolites inhibit activity of 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase (Fig. 9.2). This aizyme is critical for proper synthesis of cholesterol in phenylalanine-sensitive oligodendrocytes located in the frontal brain, especially in the prefrontal cortex. Locally synthesized cholesterol makes up approximately 30 % of all myelin lipids of the brain tissue. The function of cholesterol is not only structural but is also required for proper neuronal signal transmission [50]. Inhibition of HMG-CoA reductase by phaiylalanine is partially reversible in some individuals. This explains the improvement in myelination observed in MRl scans of poorly controlled patients who have returned to diet and have lowered their blood phenylalanine concentrations. The reduction in phenylalanine allows for proper myelin production in the phenylalanine-sensitive oligodendrocyte population [50,57,58] (Fig. 9.3). [Pg.94]

WMA) in all lobes (arrows) - female (MM) aged 27 years on low-phenylalanine diet from 3 to 8 years of age, blood phenylalanine concentration at MRl was 1,571 pmol/1, DQ 32... [Pg.96]

Fig. 9.5) after 7 months of treatment. Mean blood phenylalanine concentration was 724 pmol/L blood phenylalanine concentration at MRI was 690 pmol/L... [Pg.97]

The goal of nutrition management of phenylketonuria (PKU) is to maintain blood phenylalanine concentrations between 120 and 360 pmol/L. [Pg.101]

Frequent monitoring of blood phenylalanine concentrations is key to successful diet management... [Pg.101]


See other pages where Blood phenylalanine is mentioned: [Pg.258]    [Pg.269]    [Pg.270]    [Pg.270]    [Pg.580]    [Pg.756]    [Pg.147]    [Pg.196]    [Pg.398]    [Pg.401]    [Pg.401]    [Pg.403]    [Pg.405]    [Pg.414]    [Pg.90]    [Pg.91]    [Pg.92]    [Pg.93]    [Pg.93]    [Pg.94]   


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