The genetically-linked deficiency in the activity of hepatic phenylalanine 4-hydroxylase (EC 1.14.16.1) leads to a marked accumulation of L-phenylalanine (L-Phe) and some of its metabolic products, namely phenylpyruvate, phenyl-lactate and o-hydroxyphenylacetate, in the blood and tissues of patients with uncontrolled phenylketonuria (PKU). In order to explain the biochemical mechanisms by which...

BACKGROUND Maternal phenylketonuria (PKU) can result in multiple congenital anomalies. In Northern Ireland, the prevalence of PKU is relatively high at 1 in 4000. OBJECTIVE To assess the outcome of 39 pregnancies in 20 mothers. RESULTS Dietary control was established before conception in 17 pregnancies (44%). Five mothers with hyperphenylalaninaemia had 11 pregnancies. There were no congeni...

Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (EC 1.14.16.1). Affected patients develop elevated plasma and tissue levels of phenylalanine and its related ketoacids. Untreated patients usually exhibit severe mental retardation and poor motor function, with characteristic T2 white matter signal abnormalities on conventiona...

conclusions this finding may help improve early detection, differential diagnosis, genetic counseling, and even treatment of patients with pku. introduction phenylketonuria (pku) is an autosomal recessive inborn error of phenylalanine metabolism, which is caused by mutation in phenylalanine hydroxylase (pah) gene. most of the pah mutations are missense mutations (67%), which are followed by sma...

In untreated phenylketonuria (PKU), deficiency of phenylalanine hydroxylase (PAH) results in elevated blood phenylalanine (Phe) concentrations and severe mental retardation. Current dietary treatment prevents mental retardation, but cognitive outcome remains suboptimal. The mechanisms by which elevated blood Phe concentrations disturb cerebral metabolism and cognitive function have not been ful...

Quantitative determination of plasma phenylalanine (Phe) is essential for the diagnosis of phenylketonuria (PKU) and the control of dietary therapy of PKU patients. We have adapted a spectrophotometric method (Clin Chim Acta 1991;201:95-8) based on phenylalanine dehydrogenase (EC 1.4.1.-) for rapid and accurate determinations of Phe with the Cobas Fara II centrifugal analyzer. The method is bas...

Phenylketonuria (PKU) is characterized by phenylalanine accumulation and progressive mental retardation caused by an unknown mechanism. We demonstrate that at pathological concentrations, phenylalanine self-assembles into fibrils with amyloid-like morphology and well-ordered electron diffraction. These assemblies are specifically recognized by antibodies, show cytotoxicity that can be neutraliz...

This systematic review and meta-analysis (MA) investigates the impact of elevated blood phenylalanine (Phe) on neuropsychiatric symptoms in adults with phenylketonuria (PKU). The meta-analysis of PKU is challenging because high-quality evidence is lacking due to the limited number of affected individuals and few placebo-controlled, double-blind studies of adults with high and low blood Phe. Neu...

Oxidative stress is seen in various metabolic disorders for unknown reasons. Oxidative stress is defined as an imbalance between pro-oxidant and antioxidant status in favor of the former. This study investigated whether oxidative stress exists in phenylketonuria (PKU) using the BTBR-Pah animal model for PKU. Animals (14–24 weeks old) were sacrificed and brain and red blood cells (RBCs) were obt...