Fluctuations in phenylalanine concentrations in phenylketonuria: a review of possible relationships with outcomes

TY - JOUR

T1 - Fluctuations in phenylalanine concentrations in phenylketonuria: a review of possible relationships with outcomes

AU - Cleary, Maureen

AU - Trefz, Friedrich

AU - Muntau, Ania C

AU - Feillet, François

AU - van Spronsen, Francjan J

AU - Burlina, Alberto

AU - Bélanger-Quintana, Amaya

AU - Giżewska, Maria

AU - Gasteyger, Christoph

AU - Bettiol, Esther

AU - Blau, Nenad

AU - MacDonald, Anita

N1 - © 2013.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Fluctuations in blood phenylalanine concentrations may be an important determinant of intellectual outcome in patients with early and continuously treated phenylketonuria (PKU). This review evaluates the studies on phenylalanine fluctuations, factors affecting fluctuations, and if stabilizing phenylalanine concentrations affects outcomes, particularly neurocognitive outcome. Electronic literature searches of Embase and PubMed were performed for English-language publications, and the bibliographies of identified publications were also searched. In patients with PKU, phenylalanine concentrations are highest in the morning. Factors that can affect phenylalanine fluctuations include age, diet, timing and dosing of protein substitute and energy intake, dietary adherence, phenylalanine hydroxylase genotype, changes in dietary phenylalanine intake and protein metabolism, illness, and growth rate. Even distribution of phenylalanine-free protein substitute intake throughout 24h may reduce blood phenylalanine fluctuations. Patients responsive to and treated with 6R-tetrahydrobiopterin seem to have less fluctuation in their blood phenylalanine concentrations than controls. An increase in blood phenylalanine concentration may result in increased brain and cerebrospinal fluid phenylalanine concentrations within hours. Although some evidence suggests that stabilization of blood phenylalanine concentrations may have benefits in patients with PKU, more studies are needed to distinguish the effects of blood phenylalanine fluctuations from those of poor metabolic control.

AB - Fluctuations in blood phenylalanine concentrations may be an important determinant of intellectual outcome in patients with early and continuously treated phenylketonuria (PKU). This review evaluates the studies on phenylalanine fluctuations, factors affecting fluctuations, and if stabilizing phenylalanine concentrations affects outcomes, particularly neurocognitive outcome. Electronic literature searches of Embase and PubMed were performed for English-language publications, and the bibliographies of identified publications were also searched. In patients with PKU, phenylalanine concentrations are highest in the morning. Factors that can affect phenylalanine fluctuations include age, diet, timing and dosing of protein substitute and energy intake, dietary adherence, phenylalanine hydroxylase genotype, changes in dietary phenylalanine intake and protein metabolism, illness, and growth rate. Even distribution of phenylalanine-free protein substitute intake throughout 24h may reduce blood phenylalanine fluctuations. Patients responsive to and treated with 6R-tetrahydrobiopterin seem to have less fluctuation in their blood phenylalanine concentrations than controls. An increase in blood phenylalanine concentration may result in increased brain and cerebrospinal fluid phenylalanine concentrations within hours. Although some evidence suggests that stabilization of blood phenylalanine concentrations may have benefits in patients with PKU, more studies are needed to distinguish the effects of blood phenylalanine fluctuations from those of poor metabolic control.

KW - Adult

KW - Age Factors

KW - Biopterin

KW - Diet

KW - Humans

KW - Phenylalanine

KW - Phenylalanine Hydroxylase

KW - Phenylketonurias

KW - PubMed

U2 - 10.1016/j.ymgme.2013.09.001

DO - 10.1016/j.ymgme.2013.09.001

M3 - SCORING: Journal article

C2 - 24090706

VL - 110

SP - 418

EP - 423

JO - MOL GENET METAB

JF - MOL GENET METAB

SN - 1096-7192

IS - 4

ER -