Phenylketonuria Research Today is a free monthly online journal that collates and summarizes the latest research about Phenylketonuria, including details on genetics, causes, symptoms, hereditary disorder.

Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketonuria.

Macleod EL, Clayton MK, van Calcar SC, Ney DM

Department of Nutritional Sciences, 1415 Linden Dr., University of Wisconsin, Madison, Wisconsin, 53706, USA.

Phenylketonuria (PKU) requires a lifelong low-phenylalanine (phe) diet where protein needs are met by consumption of a phe-free amino acid (AA) formula; complaints of persistent hunger are common. Foods made with glycomacropeptide (GMP), an intact protein that contains minimal phe and may promote satiety, provide an alternative to AA formula. The objective was to assess the ability of a GMP breakfast to promote satiety and affect plasma concentrations of AAs, insulin, and the appetite stimulating hormone ghrelin in those with PKU, when compared to an AA-based breakfast. Eleven PKU subjects (8 adults and 3 boys ages 11-14) served as their own controls in an inpatient metabolic study with two 4-day treatments: an AA-based diet followed by a diet replacing all AA formula with GMP foods. Plasma concentrations of AAs, insulin and ghrelin were obtained before and/or 180min after breakfast. Satiety was assessed using a visual analog scale before, immediately after and 150min after breakfast. Postprandial ghrelin concentration was significantly lower (p=0.03) with GMP compared to an AA-based breakfast, with no difference in fasting ghrelin. Lower postprandial ghrelin concentrations were associated with greater feelings of fullness after breakfast suggesting greater satiety with GMP compared to AAs. Postprandial concentrations of insulin and total plasma AAs were higher after a GMP breakfast compared to an AA-based breakfast consistent with slower absorption and less degradation of AAs from GMP. These results show sustained ghrelin suppression, and suggest greater satiety with ingestion of a meal containing GMP compared with AAs. Some speculate their was similarities with the medifast diet but it is unproven as of yet.

Published 14 May 2010 in Mol Genet Metab.
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Articles on Phenylketonuria published 29 April 2010:

Oligodendrocyte development and myelinogenesis are not impaired by high concentrations of phenylalanine or its metabolites.   J Inherit Metab Dis, 33(2): 113-20.

Phenylketonuria (PKU) is a metabolic genetic disease characterized by deficient phenylalanine hydroxylase (PAH) enzymatic activity. Brain hypomyelination has been reported in untreated patients, but its mechanism remains unclear. We therefore investigated the influence of phenylalanine (Phe), phenylpyruvate (PP), and phenylacetate (PA) on oligodendrocytes. We first showed in a mouse model of PKU that the number of oligodendrocytes is not different in corpus callosum sections from adult mutants ... [Abstract] [Full-text]

Pahenu1 is a mouse model for tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency and promotes analysis of the pharmacological chaperone mechanism in vivo.   Hum Mol Genet, 19(10): 2039-49.

The recent approval of sapropterin dihydrochloride, the synthetic form of 6[R]-l-erythro-5,6,7,8-tetrahydrobiopterin (BH(4)), for the treatment of phenylketonuria (PKU) as the first pharmacological chaperone drug initiated a paradigm change in the treatment of monogenetic diseases. Symptomatic treatment is now replaced by a causal pharmacological therapy correcting misfolding of the defective phenylalanine hydroxylase (PAH) in numerous patients. Here, we disclose BH(4) responsiveness in ... [Abstract] [Full-text]

Articles on Phenylketonuria published 28 April 2010:

Generalized seizures aggravated by levetiracetam in an adult patient with phenylketonuria.   Metab Brain Dis.

Phenylketonuria (PKU) is one of the most common inherited metabolic disorders, which is characterized by excessive accumulation of phenylalanine (Phe) in tissues. Generalized seizures occur in 25% of the patients. Little is known about seizures and their treatment in adult PKU patients, and information with newer antiepileptic drugs is lacking. Here we report an adult patient who developed generalized seizures later in life, despite strict dietary control, and whose seizures were aggravated by ... [Abstract] [Full-text]

Articles on Phenylketonuria published 26 April 2010:

Introduction of sapropterin dihydrochloride as standard of care in patients with phenylketonuria.   Mol Genet Metab.

Sapropterin dihydrochloride, a synthetic, stable form of the tetrahydrobiopterin cofactor of phenylalanine hydroxylase, has been shown to reduce plasma phenylalanine (Phe) levels in a significant portion of patients with phenylketonuria (PKU). When we undertook introducing this medication to our PKU clinic population, the challenges of recalling and reconnecting with a variably treated and variably compliant patient population became apparent. We offered a trial of sapropterin to all of our ... [Abstract] [Full-text]

Articles on Phenylketonuria published 19 April 2010:

Unresponsiveness to tetrahydrobiopterin of phenylalanine hydroxylase deficiency.   Metabolism, 59(5): 645-52.

Conflicting results have been reported concerning the efficacy of tetrahydrobiopterin (BH4), the cofactor of phenylalanine hydroxylase, for reducing phenylalanine (Phe) concentration in phenylketonuria (PKU). We aimed to test quantitatively the effects of BH4 in PKU patients. Seven fully characterized patients were selected among a population of 130 PKU subjects as harboring PKU mutations predicted as BH4 responsive and previously considered responsive to a cofactor challenge. They received a ... [Abstract] [Full-text]

Effects of long-chain polyunsaturated fatty acid supplementation on neurodevelopment in childhood: a review of human studies.   Prostaglandins Leukot Essent Fatty Acids, 82(4): 305-14.

Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFA) are critical for infant and childhood brain development, but levels of the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are often low in the Western diet. Increasing evidence from both epidemiological and intervention studies, reviewed here, indicates that DHA supplementation, during pregnancy, lactation, or childhood plays an important role in childhood neurodevelopment. Arachidonic acid (ARA) ... [Abstract] [Full-text]

Articles on Phenylketonuria published 13 April 2010:

Comparison of adeno-associated virus pseudotype 1, 2, and 8 vectors administered by intramuscular injection in the treatment of murine phenylketonuria.   Hum Gene Ther, 21(4): 463-77.

Phenylketonuria (PKU) is caused by hepatic phenylalanine hydroxylase (PAH) deficiency and is associated with systemic accumulation of phenylalanine (Phe). Previously we demonstrated correction of murine PKU after intravenous injection of a recombinant type 2 adeno-associated viral vector pseudotyped with type 8 capsid (rAAV2/8), which successfully directed hepatic transduction and Pah gene expression. Here, we report that liver PAH activity and phenylalanine clearance were also restored in ... [Abstract] [Full-text]

Mutations of the phenylalanine hydroxylase gene in Iranian Azeri Turkish patients with phenylketonuria.   Genet Test Mol Biomarkers, 14(2): 233-5.

AIM: Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe), and production of the phenylketonuria disease. To date there have been no reports on the molecular analysis of phenylketonuria in the Iranian Azeri Turkish population. In this study, a total of 88 independent alleles from this ethnic group were investigated. RESULTS: Thirteen different ... [Abstract] [Full-text]

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