Phenylketonuria: tyrosine beyond the phenylalanine-restricted diet.

Controversies exist on the role of tyrosine in the pathogenesis of phenylketonuria (PKU) and, consequently, on the therapeutic role of tyrosine. This review examines data and theoretical considerations on the role of tyrosine in the pathogenesis and treatment of PKU. It is concluded that treatment with tyrosine alone to replace the phenylalanine-restricted diet cannot be justified.

Phenylketonuria: tyrosine supplementation in phenylalanine-restricted diets.

Treatment of phenylketonuria (PKU) consists of restriction of natural protein and provision of a protein substitute that lacks phenylalanine but is enriched in tyrosine. Large and unexplained differences exist, however, in the tyrosine enrichment of the protein substitutes. Furthermore, some investigators advise providing extra free tyrosine in addition to the tyrosine-enriched protein substitute, especially in the treatment of maternal PKU.

Behaviour and school achievement in patients with early and continuously treated phenylketonuria.

Thirty patients with early and continuously treated phenylketonuria (PKU) between 8 and 20 years of age were compared with 30 controls, matched individually for age, sex, and educational level of both parents, on behaviour rating scales for parents and teachers as well as a school achievement scale. PKU patients, as a group, demonstrated more problems in task-oriented behaviour and average academic performance than did matched controls. Interestingly, whereas male PKU patients were rated significantly lower on introversion by their teachers, female patients were rated significantly higher on introversion and lower on extraversion than matched controls.

End-stage liver disease as the only consequence of a mitochondrial respiratory chain deficiency: no contra-indication for liver transplantation.

Unlabelled: The prerequisite for liver transplantation as a therapeutic option for inherited metabolic diseases should be that the enzyme defect, being responsible for the major clinical (hepatic and/or extra-hepatic) abnormalities, is localised in the liver. Furthermore, no adequate dietary or pharmacological treatment should be available or such treatment should have an unacceptable influence on the quality of life. We report an infant, who developed end-stage liver disease with persistent lactic acidaemia in his first months of life.

Liver transplantation in mitochondrial respiratory chain disorders.

Unlabelled: Mitochondrial respiratory chain disease may lead to neonatal or late onset liver failure, requiring liver transplantation. In rare cases, the disease is restricted to the liver and the patient is cured after surgery. More frequently, other organs are simultaneously involved and neuromuscular or other extra-hepatic symptoms may pre-exist, or appear in the post-transplant follow up.

[A child with dark discoloration of urine].

In a 3-year-old boy alkaptonuria was diagnosed. From early age on gradual dark discoloration of his urine had been noticed in the diapers, but routine urinalysis had not revealed abnormalities. Alkaptonuria is a rare metabolic disease in which homogentisic acid cannot be metabolised, due to a lack of the enzyme homogentisic acid oxidase.

Phenylketonuria. The in vivo hydroxylation rate of phenylalanine into tyrosine is decreased.

In phenylketonuria (PKU), the enzyme phenylalanine hydroxylase is deficient, resulting in a decreased conversion of phenylalanine (Phe) into tyrosine (Tyr). The severity of the disease is expressed as the tolerance for Phe at 5 yr of age. In PKU patients it is assumed that the decreased conversion of Phe into Tyr is directly correlated with the tolerance for Phe.

Does impaired growth of PKU patients correlate with the strictness of dietary treatment? National Dutch PKU Steering Committee.

To assess whether growth retardation in patients with phenylketonuria (PKU) is related to the strictness of their dietary treatment, the relationship between Z scores for height up to 3 y of age and different indices of dietary control in 103 early treated Dutch PKU patients was studied. As indices of dietary control, the mean phenylalanine (Phe) concentration, the frequency of plasma Phe concentrations < 200 and < 120 micromol/l, and the standard deviation of the individual plasma Phe concentrations were studied. These measures of the dietary control were divided into quartiles.

Large daily fluctuations in plasma tyrosine in treated patients with phenylketonuria.

In patients with phenylketonuria (PKU), extra tyrosine supplementation is advocated in addition to tyrosine-enriched amino acid mixtures. PKU patients have low fasting plasma tyrosine concentrations, but little is known about tyrosine fluctuations during the day. Plasma tyrosine concentrations were studied in 12 PKU patients in response to a test without breakfast and to three tests with different tyrosine contents in breakfast and lunch: 0%/30%, 25%/30%, 50%/10%, and 75%/10% tests, reflecting the protein consumption at breakfast and lunch, respectively.

Phenylketonuria in The Netherlands: 93% of the mutations are detected by single-strand conformation analysis.

Single-strand conformational analysis was used to screen for genetic defects in all thirteen exons of the phenylalanine hydroxylase gene (PAH) in phenylketonuria and hyperphenylalaninemia patients in the Netherlands. Exons that showed a bandshift were sequenced directly. In this way, we were able to identify 93% of the PAH mutations in a panel of 34 patients.

Phenylketonuria: plasma phenylalanine responses to different distributions of the daily phenylalanine allowance over the day.

Objective: To achieve smooth control of plasma phenylalanine concentrations in phenylketonuric patients, it is advocated to divide the daily intake of natural protein and amino acid supplements equally over the meals. However, this may be quite an encumbrance for the patient. We, therefore, investigated whether a breakfast with an unequal daily distribution results in an undue rise in the plasma phenylalanine concentration.

Information processing in patients with early and continuously-treated phenylketonuria.

Unlabelled: A total of 33 patients with early and continuously-treated phenylketonuria (PKU) between 7 and 16 years of age and 33 matched controls participated in a study examining perceptual, central, and response-related mechanisms of information processing. The specific mechanisms studied were: perceptual filtering, memory search, response selection, response execution, and motor presetting. In addition, groups were compared on mean intelligence level and task oriented behaviour.

Predictors of mean phenylalanine levels during the first five years of life in patients with phenylketonuria who were treated early. Dutch National PKU Steering Committee.

We studied the relationship between plasma phenylalanine level at first diagnostic visit, country of origin of the mother, birth cohort, child clinic, sex, and social class on the one hand and mean plasma phenylalanine levels in the first five years of life on the other hand in patients with phenylketonuria (PKU) who were treated early. The study population consisted of 131 early treated patients with PKU born during the period from September 1st, 1974 to December 31st, 1988 in The Netherlands. Plasma phenylalanine levels from first diagnostic visit (usually before the age of three weeks) up until the fifth birthday were registered.

Hereditary tyrosinemia type I: a new clinical classification with difference in prognosis on dietary treatment.

Hereditary tyrosinemia type I (McKusick 27670) is a heterogeneous disease with poor prognosis, yet there are few reports of the long-term prognosis. It is therefore difficult to decide on the treatment for individual patients. We have conducted an international survey of patients with tyrosinemia type I and examined the probability of survival on dietary treatment and the causes of death in 108 patients with tyrosinemia type I.

Impaired prenatal and postnatal growth in Dutch patients with phenylketonuria. The National PKU Steering Committee.

Objective: To assess whether physical growth is affected in early treated Dutch patients with phenylketonuria (PKU).

Methods: The birth weights of all 137 early detected patients with PKU born in the period from 1974 to 1988 in the Netherlands were compared with reference values. Height, head circumference, and weight were measured at the age at which treatment started (commonly about 2-3 weeks), at 6 months of age, and yearly from the child's first birthday up to the age of 10 years.

Plasma phenylalanine and tyrosine responses to different nutritional conditions (fasting/postprandial) in patients with phenylketonuria: effect of sample timing.

Objective: To evaluate the adequacy of dietary treatment in patients with phenylketonuria, the monitoring of plasma phenylalanine and tyrosine concentrations is of great importance. The preferable time of blood sampling in relation to the nutritional condition during the day, however, is not known. It was the aim of this study to define guidelines for the timing of blood sampling with a minimal burden for the patient.

Hereditary tyrosinaemia type I: a long-term study of the relationship between the urinary excretions of succinylacetone and delta-aminolevulinic acid.

Patients with hereditary tyrosinaemia type I (HT) excrete large amounts of succinylacetone (SA) in urine. Owing to structural resemblance of SA to delta-aminolevulinic acid (ALA), SA inhibits the second enzyme in the pathway for haeme biosynthesis, porphobilinogen synthase, resulting in increased urinary ALA excretion. We investigated the relationship between urinary SA and ALA excretions of two patients with different forms of HT (late-infantile and juvenile).