Plasma Phenylalanine Levels Research Articles

A Multiplatform Metabolomics Approach to Characterize Plasma Levels of Phenylalanine and Tyrosine in Phenylketonuria.

Different pathophysiological mechanisms have been described in phenylketonuria (PKU) but the indirect metabolic consequences of metabolic disorders caused by elevated Phe or low Tyr concentrations remain partially unknown. We used a multiplatform metabolomics approach to evaluate the metabolic signature associated with Phe and Tyr. We prospectively included 10 PKU adult patients and matched controls. We analysed the metabolome profile using GC-MS (urine), amino-acid analyzer (urine and plasma) and nuclear magnetic resonance spectroscopy (urine). We performed a multivariate analysis from the metabolome (after exclusion of Phe, Tyr and directly derived metabolites) to explain plasma Phe and Tyr concentrations, and the clinical status. Finally, we performed a univariate analysis of the most discriminant metabolites and we identified the associated metabolic pathways. We obtained a metabolic pattern from 118 metabolites and we built excellent multivariate models to explain Phe, Tyr concentrations and PKU diagnosis. Common metabolites of these models were identified: Gln, Arg, succinate and alpha aminobutyric acid. Univariate analysis showed an inverse correlation between Arg, alpha aminobutyric acid and Phe and a positive correlation between Arg, succinate, Gln and Tyr (p < 0.0003). Thus, we highlighted the following pathways: Arg and Pro, Ala, Asp and Glu metabolism. We obtain a specific metabolic signature related to Tyr and Phe concentrations. We confirmed the involvement of different pathophysiological mechanisms previously described in PKU such as protein synthesis, energetic metabolism and oxidative stress. The metabolomics approach is relevant to explore PKU pathogenesis.

Four Years of Diagnostic Challenges with Tetrahydrobiopterin Deficiencies in Iranian Patients.

Hyperphenylalaninemia (HPA) is a condition caused by tetrahydrobiopterin (BH4) and phenylalanine hydroxylase (PAH) deficiencies. It is essential that differential diagnosis be conducted to distinguish these two causes of HPA, because BH4 deficiency is a more severe disease involving progressive neurologic deterioration. Based on the biological findings, HPA is defined as a plasma phenylalanine level of >2.0mg/dl (>120μmol/l). The National Biochemistry Reference Laboratory at the Pasteur Institute of Iran initiated BH4 deficiency screening tests for the first time during the implementation of a nationwide phenylketonuria (PKU) screening program. Measurement of blood phenylalanine and urinary neopterin and biopterin was conducted by high-performance liquid chromatography in 617 patients with HPA. Dihydropteridine reductase (DHPR) activity was measured in all patients by kinetic spectrophotometry. Differential diagnosis was conducted for PKU, transient HPA, and BH4 deficiencies.Our results indicated that out of 76 cases involving BH4 deficiencies, 37 had 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency, 35 had DHPR deficiency, 1 case had pterin-4a-carbinolamine dehydratase (PCD) deficiency, and 3 cases had GTP cyclohydrolase I (GTPCH) deficiency. In this study, 1 novel deletion mutation and 18 novel missense mutations were reported in addition to mutations that had previously been identified and registered in BIOMDB. At present, the screening program for PKU in Iran includes tests that detect different forms of BH4 deficiency presenting with HPA. Newborns that are BH4-deficient benefit from the availability of the tests because they can receive necessary care before being clinically affected.

Dietary phenylalanine requirement and tyrosine replacement value for phenylalanine of juvenile blunt snout bream, Megalobrama amblycephala

Two 9-week experiments were conducted to estimate the dietary phenylalanine requirement and the tyrosine replacement value for phenylalanine of juvenile blunt snout bream. In experiment I, six isonitrogenous and isoenergetic experimental diets were formulated to contain graded levels of phenylalanine ranging from 0.51% to 2.04% of the diet at a constant dietary tyrosine level (1.07% of dry diet). Weight gain (WG), specific growth rate (SGR), feed efficiency ratio (FER) and protein efficiency ratio (PER) increased with increasing dietary phenylalanine levels up to 1.11%, and thereafter declined. The whole body moisture, crude protein and lipid contents were significantly affected by dietary phenylalanine levels, while no significant difference was found in ash among dietary treatments. Plasma phenylalanine level significantly increased with increasing dietary phenylalanine level, whereas alkaline phosphatase (AKP) activity showed a reversed trend. Dietary phenylalanine level significantly affected plasma glucose concentration. Using quadratic regression analysis of SGR and FER, the dietary phenylalanine requirement was estimated to be 0.93% of diet (2.74% of dietary protein) and 1.01% of diet (2.97% of dietary protein), respectively. In experiment II, six diets with graded levels of l-tyrosine ranging from 0.45% to 1.34% of diet (with fixed phenylalanine level, 0.82%) were formulated to investigate the tyrosine replacement value for phenylalanine. Based on SGR and FER, the tyrosine replacement value for phenylalanine in juvenile blunt snout bream was estimated to be 50.0% and 50.6% on a weight basis or 45.6% and 46.1% on a molar basis, respectively. Above all, the total aromatic amino acid requirement was calculated to be 1.86% and 2.04% of diet (5.47% and 6.00% of dietary protein) on the basis of SGR and FER, respectively. Considering excess dietary phenylalanine resulted in reduced growth performance, the dietary total aromatic amino acid should not exceed 3.44% of diet (10.1% of dietary protein).

Serum phenylalanine in preterm newborns fed different diets of human milk

ObjectiveTo evaluate phenylalanine plasma profile in preterm newborns fed different human milk diets. MethodsTwenty‐four very‐low weight preterm newborns were distributed randomly in three groups with different feeding types: Group I: banked human milk plus 5% commercial fortifier with bovine protein, Group II: banked human milk plus evaporated fortifier derived from modified human milk, Group III: banked human milk plus lyophilized fortifier derived from modified human milk. The newborns received the group diet when full diet was attained at 15 ± 2 days. Plasma amino acid analysis was performed on the first and last day of feeding. Comparison among groups was performed by statistical tests: one way ANOVA with Tukey's post‐test using SPSS software, version 20.0 (IBM Corp, NY, USA), considering a significance level of 5%. ResultsPhenylalanine levels in the first and second analysis were, respectively, in Group I: 11.9 ± 1.22 and 29.72 ± 0.73; in Group II: 11.72 ± 1.04 and 13.44 ± 0.61; and in Group III: 11.3 ± 1.18 and 15.42 ± 0.83μmol/L. ConclusionThe observed results demonstrated that human milk with fortifiers derived from human milk acted as a good substratum for preterm infant feeding both in the evaporated or the lyophilized form, without significant increases in plasma phenylalanine levels in comparison to human milk with commercial fortifier.

Melatonin and Dopamine as Biomarkers to Optimize Treatment in Phenylketonuria: Effects of Tryptophan and Tyrosine Supplementation

To determine whether additional supplementation of tryptophan (Trp) and tyrosine (Tyr) improve serotonin and dopamine metabolism in individuals with phenylketonuria treated with large neutral amino acid (LNAA) tablets. Ten adult individuals with phenylketonuria participated in a randomized, double-blind, placebo-controlled cross-over study consisting of three 3-week phases: washout, treatment with LNAA tablets plus supplementation with either Trp and Tyr tablets or placebo, and LNAA tablets plus the alternate supplementation. An overnight protocol to measure blood melatonin, a serotonin metabolite in the pinealocytes, and urine 6-sulfatoxymelatonin and dopamine in first-void urine specimens was conducted after each phase. Serum melatonin and urine 6-sulfatoxymelatonin and dopamine levels were increased in the LNAA phase (LNAA plus placebo) compared with the washout phase. Serum melatonin and urine 6-sulfatoxymelatonin were not increased in the active phase (LNAA plus Trp + Tyr) compared with the LNAA phase, although plasma Trp:LNAA was increased compared with the LNAA phase. Among 7 subjects with a plasma Trp/LNAA >0.03, a negative correlation between urine 6-sulfatoxymelatonin and plasma phenylalanine levels was observed (r = -0.072). Urine dopamine levels and plasma Tyr:LNAA were increased in the active phase compared with the LNAA phase. Melatonin levels were not increased with the higher dose of Trp supplementation, but dopamine levels were increased with the higher dose of Tyr supplementation. Serotonin synthesis appears to be suppressed by high phenylalanine levels at the Trp hydroxylase level.

Serum phenylalanine in preterm newborns fed different diets of human milk

ObjectiveTo evaluate phenylalanine plasma profile in preterm newborns fed different human milk diets. MethodsTwenty-four very-low weight preterm newborns were distributed randomly in three groups with different feeding types: Group I: banked human milk plus 5% commercial fortifier with bovine protein, Group II: banked human milk plus evaporated fortifier derived from modified human milk, Group III: banked human milk plus lyophilized fortifier derived from modified human milk. The newborns received the group diet when full diet was attained at 15 ± 2 days. Plasma amino acid analysis was performedon the first and last day of feeding. Comparison among groups was performed by statistical tests: one way ANOVA with Tukey's post-test using SPSS software, version 20.0 (IBM Corp, NY, USA), considering a significance level of 5%. ResultsPhenylalanine levels in the first and second analysis were, respectively, in Group I: 11.9 ± 1.22 and 29.72 ± 0.73; in Group II: 11.72 ± 1.04 and 13.44 ± 0.61; and in Group III: 11.3 ± 1.18 and 15.42 ± 0.83μmol/L. ConclusionThe observed results demonstrated that human milk with fortifiers derived from human milk acted as a good substratum for preterm infant feeding both in the evaporated or the lyophilized form, without significant increases in plasma phenylalanine levels in comparison to human milk with commercial fortifier.

Elevated Levels of Plasma Phenylalanine in Schizophrenia: A Guanosine Triphosphate Cyclohydrolase-1 Metabolic Pathway Abnormality?

BackgroundPhenylalanine and tyrosine are precursor amino acids required for the synthesis of dopamine, the main neurotransmitter implicated in the neurobiology of schizophrenia. Inflammation, increasingly implicated in schizophrenia, can impair the function of the enzyme Phenylalanine hydroxylase (PAH; which catalyzes the conversion of phenylalanine to tyrosine) and thus lead to elevated phenylalanine levels and reduced tyrosine levels. This study aimed to compare phenylalanine, tyrosine, and their ratio (a proxy for PAH function) in a relatively large sample of schizophrenia patients and healthy controls.MethodsWe measured non-fasting plasma phenylalanine and tyrosine in 950 schizophrenia patients and 1000 healthy controls. We carried out multivariate analyses to compare log transformed phenylalanine, tyrosine, and phenylalanine:tyrosine ratio between patients and controls.ResultsCompared to controls, schizophrenia patients had higher phenylalanine (p<0.0001) and phenylalanine: tyrosine ratio (p<0.0001) but tyrosine did not differ between the two groups (p = 0.596).ConclusionsElevated phenylalanine and phenylalanine:tyrosine ratio in the blood of schizophrenia patients have to be replicated in longitudinal studies. The results may relate to an abnormal PAH function in schizophrenia that could become a target for novel preventative and interventional approaches.

Impaired Cognitive Functioning in Patients with Tyrosinemia Type I Receiving Nitisinone

To examine cognitive functioning in patients with tyrosinemia type I treated with nitisinone and a protein-restricted diet. We performed a cross-sectional study to establish cognitive functioning in children with tyrosinemia type I compared with their unaffected siblings. Intelligence was measured using age-appropriate Wechsler Scales. To assess cognitive development over time, we retrieved sequential IQ scores in a single-center subset of patients. We also evaluated whether plasma phenylalanine and tyrosine levels during treatment was correlated with cognitive development. Average total IQ score in 10 patients with tyrosinemia type I receiving nitisinone was significantly lower compared with their unaffected siblings (71 ± 13 vs 91 ± 13; P = .008). Both verbal and performance IQ subscores differed (77 ± 14 vs 95 ± 11; P < .05 and 70 ± 11 vs 87 ± 15; P < .05, respectively). Repeated IQ measurements in a single-center subset of 5 patients revealed a decline in average IQ score over time, from 96 ± 15 to 69 ± 11 (P < .001). No significant association was found between IQ score and either plasma tyrosine or phenylalanine concentration. Patients with tyrosinemia type I treated with nitisinone are at risk for impaired cognitive function despite a protein-restricted diet.

Erythrocytes encapsulated with phenylalanine hydroxylase exhibit improved pharmacokinetics and lowered plasma phenylalanine levels in normal mice

Enzyme replacement therapy is often hampered by the rapid clearance and degradation of the administered enzyme, limiting its efficacy and requiring frequent dosing. Encapsulation of therapeutic molecules into red blood cells (RBCs) is a clinically proven approach to improve the pharmacokinetics and efficacy of biologics and small molecule drugs. Here we evaluated the ability of RBCs encapsulated with phenylalanine hydroxylase (PAH) to metabolize phenylalanine (Phe) from the blood and confer sustained enzymatic activity in the circulation. Significant quantities of PAH were successfully encapsulated within murine RBCs (PAH-RBCs) with minimal loss of endogenous hemoglobin. While intravenously administered free PAH enzyme was rapidly eliminated from the blood within a few hours, PAH-RBCs persisted in the circulation for at least 10days. A single injection of PAH-RBCs was able to decrease Phe levels by nearly 80% in normal mice. These results demonstrate the ability of enzyme-loaded RBCs to metabolize circulating amino acids and highlight the potential to treat disorders of amino acid metabolism.

Testing for Tetrahydrobiopterin Responsiveness in Patients with Hyperphenylalaninemia due to Phenylalanine Hydroxylase Deficiency

Pharmacological levels of the phenylalanine hydroxylase enzyme cofactor, tetrahydrobiopterin (BH4), reduce plasma phenylalanine levels in some patients with phenylketonuria (PKU), providing the first pharmacological therapy for PKU. Responsiveness to this therapy must be determined empirically through a BH4 loading test or trial. The authors have analyzed the loading tests currently in use in light of the numerous factors that can influence their results. Sapropterin dihydrochloride is a stable, synthetic form of BH4 approved for treatment of PKU in responsive patients. An expert panel identified evidence from published reports of clinical experience. Reports of research involving at least 25 patients and published in English were considered. In all, 14 studies met both criteria; eight employing the sapropterin dihydrochloride preparation from Schircks Laboratories and six the sapropterin dihydrochloride preparation from Biomarin/Merck Serono. The arbitrary responsiveness definition of a >30% reduction in blood phenylalanine appears to be a good compromise between sensitivity and specificity for the initial screening test. However, individual patient characteristics should be considered when interpreting results, especially in patients with low baseline phenylalanine levels.

Is Melatonin Synthesis a New Biomarker for the Pathogenesis and Treatment of Phenylketonuria?

Is Melatonin Synthesis a New Biomarker for the Pathogenesis and Treatment of Phenylketonuria?

Plasma Amino Acid Profiles in Collagen Disease Patients with Interstitial Lung Disease

Interstitial lung disease (ILD) is frequently associated with collagen diseases, and is designated collagen vascular disease-associated ILD (CVD-ILD) that influences the prognosis of the disease. Acute-onset diffuse ILD (AoDILD) occurs in patients with collagen disease with or without underlying CVD-ILD. The prognosis of AoDILD is quite poor. It has been reported that plasma amino acid profiles are altered in rheumatoid arthritis (RA) patients. Here, we investigated the plasma amino acid profiles to determine whether they may be useful for diagnosing CVDILD or AoDILD in collagen disease. Plasma amino acid levels were analyzed using liquid chromatography/electrospray ionization tandem mass spectrometry in 64 RA patients with or without CVD-ILD, and 15 collagen disease patients with AoDILD. By using support vector machine (svm) analysis, the svm index (AA) was generated from amino acid profiles and the svm index (AA, KL6) was from amino acid profiles together with Krebs von den lungen-6 (KL-6). Plasma lysine levels were higher in RA patients with ILD than in those without. The optimized cut-off level of svm index (AA) was determined for CVD-ILD in RA, and the specificity and the sensitivity were 86.8% and 65.4%, respectively. These values for the svm index (AA, KL6) were 81.6% and 88.5%. The plasma methionine and phenylalanine levels were significantly increased in the AoDILD state, whereas Fischer’s ratio was decreased. This is the first report of plasma amino acid profiles in CVD-ILD and AoDILD in collagen disease. The svm index (AA, KL6) will be a better marker for diagnosing CVD-ILD in RA than KL-6 alone, though svm index (AA) is not. The plasma amino acid profiles could be a better marker for AoDILD in collagen disease patients.

An integrated plasma and urinary metabonomic study using UHPLC–MS: Intervention effects of Epimedium koreanum on ‘Kidney-Yang Deficiency syndrome’ rats

A metabonomic strategy based on UHPLC–MS with principal component analysis was developed to investigate the intervention effects of Epimedium koreanum on metabolism characters of ‘Kidney-Yang Deficiency syndrome’ rats. The rats were injected intraperitoneally hydrocortisone once daily for 15 days to simulate ‘Kidney-Yang Deficiency syndrome’ and then administered orally E. koreanum extract once daily for the following 15 days. Plasma and urine samples before hydrocortisone injection, on day 15 of hydrocortisone injection and on days 3, 6, 9, 12, 15 exposed to E. koreanum extract were collected. Significant metabolic disorders were observed in ‘Kidney-Yang Deficiency syndrome’ rats and sixteen potential biomarkers were identified. The disturbed plasma levels of phenylalanine, tryptophan, cholic acid, lysophosphatidylcholines and urinary levels of phenylalanine, hippurate, phenylacetylglycine, N2-succinyl-l-ornithine, creatinine, α-ketoglutarate, citrate, phenol sulfate, indoxyl sulfate, cresol sulfate in model rats were gradually restored to normal after administration of E. koreanum extract, which indicated that E. koreanum had time-dependent recovering effects via regulating oxidant–antioxidant balance, amino acid metabolism, lipid metabolism, energy metabolism, and gut microflora. This work highlights that metabonomics is a promising tool for studying the essence of Chinese medicine's syndrome theory and the action mechanism of traditional Chinese medicine, and provides scientific and reasonable information on safety and efficacy of traditional Chinese medicine.

Metabolomic profiling in blood from umbilical cords of low birth weight newborns

BackgroundLow birth weight has been linked to an increased risk to develop obesity, type 2 diabetes, and hypertension in adult life, although the mechanisms underlying the association are not well understood. The objective was to determine whether the metabolomic profile of plasma from umbilical cord differs between low and normal birth weight newborns.MethodsFifty healthy pregnant women and their infants were selected. The eligibility criteria were being born at term and having a normal pregnancy. Pairs were grouped according to their birth weight: low birth weight (LBW, birth weight < 10th percentile, n = 20) and control (control, birth weight between the 75th-90th percentiles, n = 30). Nuclear Magnetic Resonance (NMR) was used to generate metabolic fingerprints of umbilical cord plasma samples. Simultaneously, the metabolomic profiles of the mothers were analysed. The resulting data were subjected to chemometric, principal component and partial least squares discriminant analyses.ResultsUmbilical cord plasma from LBW and control newborns displayed a clearly differentiated metabolic profile. Seven metabolites were identified that discriminate the LBW from the control group. LBW newborns had lower levels of choline, proline, glutamine, alanine and glucose than did the control newborns, while plasma levels of phenylalanine and citrulline were higher in LBW newborns (p < 0.05). No significant differences were found between the two groups of mothers.ConclusionsLow birth weight newborns display a differential metabolomic profile than those of normal birth weight, a finding not present in the mothers. The meaning and the potential utility of the findings as biomarkers of risk need to be addressed in future studies.

Update on the treatment of phenylketonuria: long-term safety and efficacy of sapropterin dihydrochloride

Correspondence: Hilary Vernon Blalock 1008, 600 North Wolfe Street, Baltimore, MD 21287, USA Tel +1 410 955 3071 Fax +1 410 614 9246 Email hvernon1@jhmi.edu Abstract: Phenylketonuria (PKU) is an inborn error of metabolism caused by a defect in the enzyme phenylalanine hydroxylase, which is responsible for converting phenylalanine to tyrosine. Untreated, this disorder will result in severe intellectual disability. However, with proper management, outcome is excellent. For many years, this disorder was managed exclusively with dietary measures which consisted of a phenylalanine-restricted diet. However, with the recent introduction of a stable, orally bioavailable form of tetrahydrobiopterin (BH4), the cofactor for phenylalanine hydroxylase, treatment in this disorder has been drastically altered. This stable form of BH4, sapropterin dihydrochloride, has a very good safety profile and is very effective in many patients with PKU in lowering plasma phenylalanine levels and allowing for liberalization of the phenylalanine-restricted diet. The introduction of BH4 has posed many new challenges in the treatment of PKU, including developing the best protocol to determine whether or not a patient will respond to BH4, and how to treat atypical populations including young children, fully affected, untreated adults, and pregnant patients. In this review, we will examine the history of treatment in PKU, the history of treatment with BH4, protocol options for determining if a patient is a drug responder, and considerations for treatment in special populations.

The use of parenteral nutrition for the management of PKU patient undergoing chemotherapy for lymphoma: A case report

The metabolic control of phenylalanine levels is a challenge during illness. We present the metabolic management of a 6year old boy with classical PKU who was diagnosed with stage III intraabdominal Burkit's lymphoma and underwent surgical resection and chemotherapy. The metabolic control during chemotherapy was achieved by the use of parenteral custom made amino acid solution and pro-active adjustment of intake. From the 94 obtained plasma phenylalanine (Phe) levels, 18.4% were above our clinic's recommended upper limit (360μmol/L, 6mg/dL) while 52.7% of Phe levels were below the recommended lower limit (120μmol/L, 2mg/dL). Phe levels above recommended range were associated with low caloric/protein intake, while levels below recommended range reflected the difficulty in achieving the full prescribed Phe intake. We recommend early institution of custom made amino acid solution with maximum amino acid content and caloric intake to provide optimal phenylalanine control. Administration of phenylalanine via regular intravenous amino acid solution may assist in avoiding low Phe levels when prescribed intake is compromised due to vomiting and other disease related illnesses.Use of custom made, phenylalanine free amino acid solution proved beneficial in the management of blood phenylalanine levels in a PKU patient during chemotherapy for Burkitt lymphoma.

Changes in plasma phenylalanine, isoleucine, leucine, and valine are associated with significant changes in intracranial pressure and jugular venous oxygen saturation in patients with severe traumatic brain injury

Changes in plasma aromatic amino acids (AAA=phenylalanine, tryptophan, tyrosine) and branched chain amino acids (BCAA=isoleucine, leucine, valine) levels possibly influencing intracranial pressure (ICP) and cerebral oxygen consumption (SjvO(2)) were investigated in 19 sedated patients up to 14days following severe traumatic brain injury (TBI). Compared to 44 healthy volunteers, jugular venous plasma BCAA were significantly decreased by 35% (p<0.001) while AAA were markedly increased in TBI patients by 19% (p<0.001). The BCAA to AAA ratio was significantly decreased by 55% (p<0.001) which persisted during the entire study period. Elevated plasma phenylalanine was associated with decreased ICP and increased SjvO(2), while higher plasma isoleucine and leucine levels were associated with increased ICP and higher plasma leucine and valine were linked to decreased SjvO(2). The amount of enterally administered amino acids was associated with significantly increased plasma levels with the exception of phenylalanine. Contrary to the initial assumption that elevated AAA and decreased BCAA levels are detrimental, increased plasma phenylalanine levels were associated with beneficial signs in terms of decreased ICP and reduced cerebral oxygen consumption reflected by increased SjvO(2); concomitantly, elevated plasma isoleucine and leucine levels were associated with increased ICP while leucine and valine were associated with decreased SjvO(2) following severe TBI, respectively. The impact of enteral nutrition on this observed pattern must be examined prospectively to determine if higher amounts of phenylalanine should be administered to promote beneficial effects on brain metabolism and if normalization of plasma BCAA levels is without cerebral side effects.

Bone development in children and adolescents with PKU

Individuals with phenylketonuria (PKU, OMIM 261600) have shown bone disease from childhood. Factors such as non-adherence to treatment, nutritional inadequacy, and high phenylalanine levels are associated with bone disease in several studies. This research aimed to describe the impact of dietary factors (consumption of energy, protein, calcium, phosphorus, and phenylalanine), and the control of plasma phenylalanine levels on bone age (BA) and bone mineral density (BMD). Thirteen patients of both genders, from 8 to 16 years old participated in this study. Control data were collected of phenylalanine levels, food frequency and record, hand and fist X-rays, and spinal bone densitometry. In children group (CG), individuals non-adherent to diet (NAD) consumed lower amounts of calcium (472 ± 100 mg/day) and energy (1743 ± 486 Kcal); they had higher rates of phenylalanine (564 ± 94 μmol/L) in blood, intake phenylalanine (701 ± 334 mg/g), and higher protein intake from free foods (14 ± 6.67 g/day); bone age (BA) values higher than the chronological age (CA) and less BMD values (-0.7 ± 1.6 SD) also were verified. In adolescent group (AG, N = 8) of NAD, values were lower for energy intake (1379 ± 258 Kcal), calcium (801 ± 152 mg/day), phosphorus (657 ± 102 mg/day), food protein (25 ± 7.6 g/day), and intake phenylalanine (1067 ± 382 mg/day) than recommended. Higher levels of plasma phenylalanine (851 ± 244 μmol/L), bone age greater than chronological age and lower BMD values (-2.4 ± -2.5 SD) were observed. The results suggest effects on BA and on BMD, in both children and adolescent groups. The bone development is expressed differently in children and adolescents. The non-adherence to the diet verified in both groups and the consequent imbalance in the nutrients intake involved in bone metabolism suggest that these factors influence the failure to thrive in children and reduced bone mineralization in adolescents.

Neuropsychological outcome of NTBC-treated patients with tyrosinaemia type 1

Corinne De Laet, Vanessa Terrones Munoz, Jaak Jaeken, Baudouin FranAois, Dietbrandt Carton, Etienne M Sokal, Bernard Dan, Philippe J Goyens 1 Nutrition and Metabolism Unit, H pital Universitaire des Enfants Reine Fabiola, Universit Libre de Bruxelles (ULB), Brussels, Belgium. 2 Centre for Metabolic Diseases, University Hospital Gasthuisberg, Leuven, Belgium. 3 Pinocchio Centre for Inborn Metabolic Diseases, Esperance Hospital, Li ge, Belgium. 4 Centre for Metabolic Diseases, Ghent University Hospital, Ghent, Belgium. 5 Paediatric Department, St Luc Clinics, Brussels, Belgium. Correspondence to: corinne.delaet@huderf.be

Impact of complicated intra-abdominal infection on albumin synthesis rate

To study the impact of complicated intra-abdominal infections on albumin synthesis rate. Eight patients with complicated intra-abdominal infections associated with intestinal fistula were admitted to the Research Institute of General Surgery at the Jinling Hospital between December 2009 and October 2010. Eight healthy volunteers matched for age, sex, and body mass index were enrolled as controls. All the subjects were given a primed, constant infusion of sterile L-[ring-(2)H(5)]-phenylalanine solution (priming dose: 4 μmol/kg, infusion rate: 6 μmol·kg(-1)·min(-1)) via peripheral venous lines in fast state. Arterial blood samples(3 ml) were drawn before and throughout the infusion at hourly intervals. The enrichment of L-[ring-(2)H(5)]-phenylalanine from the plasma free amino acid pool and from albumin were determined by gas chromatography/mass spectrometry analysis. Both plasma total protein concentration(62.2±1.0) g/L and plasma albumin concentration (32.5±4.0) g/L in patients with complicated intra-abdominal infection were lower compared with controls[(74.2±1.7) g/L and (46.1±2.6) g/L, both P<0.05]. Body temperature, neutrophil count and plasma C-reactive protein concentration in patients with infection were significantly greater than the levels in control subjects(P<0.05). Albumin synthesis rate in patients with intra-abdominal infection was significantly lower than that in the control group [(5.3±1.6)%/d and (7.8±1.2)%/d respectively, P<0.05]. The measurement of plasma free amino acid concentration showed that plasma glutamic acid level was greater than that in control subjects, and that plasma phenylalanine and proline levels were lower than those in controls. Complicated intra-abdominal infection inhibits albumin synthesis rate in patients with intestinal fistula, which may partially contribute to the decrease of plasma albumin concentration.