Dried blood spot (DBS) microsampling is extensively employed in newborn screening (NBS) and neonatal studies. However, the impact of variable neonatal hematocrit (Ht) values on the results can be a source of analytical error, and the use of fixed Ht for calibration (Htcal) is not representative of all neonatal subpopulations. A computational approach based on neonatal demographics was developed and implemented in R® language to propose a strategy using correction factors to address the Ht effect in neonatal DBS partial-spot assays. A rational "tolerance level" was proposed for the Ht effect contribution to the total analytical error and a safe Ht range for neonatal samples, where the correction of concentrations can be omitted. Furthermore, an "alert zone" for a false positive or negative result in NBS was proposed, where the Ht effect has to be considered. Results point toward the use of Htcal values closely representative of populations under analysis and an acceptable level of percentage relative error can be attributed to the Ht effect, diminishing the probability of correction. Overall, the impact of the Ht effect on neonatal studies is important and future work may further investigate this parameter, correlated to other clinical variables potentially affecting results.

Amino acid neurotransmitters, including glutamate, phenylalanine, tyrosine, alanine, and glycine, underlie the majority of the excitatory and inhibitory neurotransmission in the nervous system, and acute exercise has been shown to modulate their concentrations. We aimed to determine whether any correlation exists between the above-mentioned amino acid blood concentrations and the neuropsychological performance after an acute exercise intervention. Sixty basketball players were randomly assigned to one of two experimental conditions: exercise or inactive resting. All participants underwent a comprehensive neuropsychological assessment and blood samples were taken on a Guthrie card before and after the end of the experimental conditions. Amino acid blood concentrations were significantly elevated and cognitive performance significantly improved post-exercise on specific neuropsychological assessments. Significant intervention × group interaction effects were apparent for Trail Making Test part-B [F(1,58) = 20.46, p < .0001, η2 = .26] and Digit Span Backwards [F(1,58) = 15.47, p < .0001, η2 = .21] neuropsychological assessments. Additionally, regression analysis indicated that tyrosine accounted for 38.0% of the variance in the Trail Making Test part-A test. These results suggest that elevated blood concentrations of neurotransmission-related amino acids are associated with improved neuropsychological performance after a single bout of high-intensity exercise.

Obejctives: Phenylketonuria (PKU) and hyperphenyla laninemia (HPHE) are metabolic disorders of phenylalanine (phe) metabolism due to the liver enzyme phe hydroxylase deficiency resulting in mental retardation. The only treatment of these disorders is the total or the partial breastfeeding replacement with special formula, respectively. Case presentation: We aimed to evaluate the maternal stress degree in the two groups of mothers and compare the stress degree between mothers who were obliged to replace breastfeeding completely with those who replaced it partially. Mothers (n=50) were divided into two groups: n=25 with PKU and n=25 with HPHE infants. Mothers with PKU newborns were obliged to replace breastfeeding completely and feed their newborns with a common formula plus phe free medical food, whereas mothers with HPHE infants partially replaced breastfeeding with phe free medical food. Stress degrees were calculated using special questionnaire checklist by Bourne E. Psychological support was provided for both groups of mothers with stress. Conclusions: Most mothers with PKU infants experienced high or severe stress, whereas mothers with HPHE newborns suffered from low and moderate symptoms and signs of stress. After psychological support most mothers with PKU newborns were ameliorated from stress symptoms; mothers with HPHE neonates experienced almost no stress symptoms. Mothers with PKU infants obliged to complete breastfeeding replacement experienced high and/or severe stress degrees as compared to mothers with HPHE newborns with partial breastfeeding replacement. Psychological support resulted in amelioration of both tested groups.

Abstract Objectives Medium-chain (MCA) and long-chain acylcarnitine (LCA) blood concentrations play a significant role in the fatty acid (FA) oxidation process, especially during the first days of life. Identification of their abnormal concentrations, via expanded newborn screening, can lead to the diagnosis of FA oxidation disorders. This study aimed to demonstrate MCA and LCA concentrations in Dried Blood Spots (DBS) of full-term breastfed infants, in relation to their birth weight (BW) perinatally. Methods Breastfed full-term infants (n = 12,000, 6,000 males, 6,000 females) with BW 2,000–3,999 g were divided into four equal groups: Group A, 2,000–2,499 g, B 2,500–2,999 g, C 3,000–3,499 g, and D 3,500–3,999 g. Samples were collected as DBS and acylcarnitines were determined via a liquid chromatography tandem mass spectrometry method. Results MCA and LCA blood concentrations were determined significantly lower in group A (low birth weight infants) in both sexes. Infants with BW > 3,500 g (group D), were characterized by lower levels of C10, C10:1, C14, C14:1 acylcarnitines and higher levels of C16 and C18:1 acylcarnitines, as compared to the other groups of this study. Conclusions Concentration patterns in full-term breastfed newborns in relation to sex and mainly BW found in this study could be very helpful for neonatologists, especially for newborns of group A.

BACKGROUND:Free carnitine (C0) and short chain acylcarnitine (SCA) blood concentrations play a significant role in fatty acid oxidation process during the first days of life. The aim of this study was to demonstrate C0 and SCA concentrations in Dried Blood Spots (DBS) of full term breastfed infants in relation to their birth weight (BW) perinatally. METHODS:Breastfed full term infants (n = 12,000, 6000 males, 6000 females) with BW 2000-4000 g were divided into 4 equal groups: Group A, 2000-2500 g, B 2500-3000 g, C 3000-3500 g and D 3500-4000 g. Blood samples in the form of DBS were collected on the 3rd day of life and analyzed via a liquid chromatography tandem mass spectrometry (LC-MS/MS) protocol. RESULTS:BW-related C0 and SCAs were found as follows: C0 was determined to be statistically significantly higher in group A (BW 2000-2500 g) in both males and females. Lower acetylcarnitine (C2) and hydroxybutyrylcarnitine (C4OH) blood concentrations were detected in group A of both sexes, whereas butyrylcarnitine (C4) concentrations were found to be lower in the same group of males only. Furthermore, high concentrations of C2 and C4OH were shown in group D (BW 3500-4000 g) in both sexes. SCA sum of means ± SD values in males and females of group A were statistically significantly lower as compared to other study groups. CONCLUSION:Due to the number of the samples, data from this study could be applied as neonatal screening reference values for full term breastfed newborns in relation to their birth weight.

Objectives Self-esteem is the degree to which the qualities and characteristics contained in one's self-concept are perceived to be positive. The aim of this study was to evaluate the self-esteem scores in phenylketonuria (PKU) patients on "strict", "loos" and "off diet". Sixty PKU patients were divided in three equal groups. Methods Group a: "on strict", group b: "on loos" and group c: "off diet". A special questionnaire for self-esteem scores was created for these patients. Results Before psychological support, group a patients demonstrated 6/20 (30%) very high self-esteem, 9/20 (45%) high and 5/25 (25%) moderate. After support 14/20 (70%) were turned to very high, 5/20 (25%) represented high except one whose degrees remained an altered. group b 4/20 (20%) were very high, 7/20 (35%) were high, 3/20 (15%) moderate and the rest of them showed low self-esteem degrees, after support, 10/20 (50%) showed very high, 5/20 (25%) became high, 3/20 (15%) turned to moderate and 2/20 (10%) remained unaltered. Group c, 1/20 (5%) were very high self-esteemed, 7/20 (35%) were high, 6/20 (30%) were moderate and 6/20 (30%) with low self-esteemed, at the end of support, 6/20 (30%) become very high, 8/20 (40%) with high, 4/20 (20.0%), moderate self-esteem whereas the rest were unaltered. Conclusions Very high and high self-esteem degrees were demonstrated in patients who follow their PKU diet. Moderate and low self-esteem degrees were predominantly found in patients on loos and or off diet. Psychological supports commonly result in amelioration of self-esteem degrees.

Background: The amino acids glutamine plus glutamate, phenylalanine and tyrosine are implicated in neurotransmission. We aimed to evaluate these amino acid blood concentrations in full-term breastfed infants with -different birth weight (BW) perinatally. Methods: Breastfed full-term infants (n = 6000, males 3000, females 3000) BW 2000-4000 g were divided into four equal groups. Both males and females Groups A, 2000-2500 g, B 2500-3000 g, C 3000-3500 g, D 3500-4000 g. Blood samples on Guthrie cards, were taken on the 3rd day of life and quantified via a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Results: Glutamine plus glutamate mean values were found to be statistically significantly different between males vs. females in all the studied groups. The highest values were determined in both males and females in group D. Statistically significantly higher values of phenylalanine appeared in group D vs. other groups. Tyrosine mean values were calculated to be statistically significantly different in both sexes in group A compared to other groups. Conclusions: Differences of glutamine plus glutamate, phenylalanine and tyrosine levels among full-term newborns with different BW are presented for the first time in the literature. Newborns with BW 3000-4000 g are benefited by having higher concentrations of the mentioned neurotransmission related amino acids. Neonatal screening reference values for these amino acids in relation to BW could be established, not only for preterm and low BW infants but also for full-term newborns with BW >3000 g.

There are twenty-one amino acids in the human body and some of them have neurotransmission action during exercise. The aim of this review is to present the increase of neurotransmission amino acids in the blood after training. Additionally, we highlight the neurotransmission action of certain amino acids and their beneficial effects on a wide range of neurological disorders. A Medline and Scopus search was performed to identify articles published on this topic. Only articles published in English were considered. Cognitive functioning of memory, attention, arousal, as well as motor control and emotion functioning, are related to modifications in the glutamatergic, monoaminergic and serotonergic systems in patients with some types of dementia. A direct effect of phenylalanine on certain neurotransmission enzymes is also described. Tyrosine is highly involved in dopamine production, resulting in amelioration of the symptoms of patients with moderate Parkinson’s disease via dopamine increase. Training could be beneficial, not only to healthy people but also to patients with moderate neurodegenerative disorders.

Essential, non-essential and conditionally essential amino acid blood concentrations play a critical role in newborns. We aimed to quantitate most of these amino acids in the blood of full-term breastfed infants, perinatally and correlate the obtained values with their birth weight. Breastfed full-term infants (n = 12,000; 6000 males, 6000 females) with birth weight 2000-4000 g were divided into 4 equal groups: Group A, 2000-2500 g; B, 2500-3000 g; C, 3000-3500 g and D, 3500-4000 g. Blood samples as Dried Blood Spots (DBS) were collected on the 3rd day of life and analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) protocol. Blood concentrations of the amino acids, Phenylalanine, Leucine, Glutamine, Ornithine, Alanine, Tyrosine and Glycine in full-term breastfed newborns, were found to be related to their birth weight, perinatally. On the contrary, no relationship between birth weight and blood concentrations of the amino acids Valine, Methionine, Citrulline and Arginine was found. Due to the number of the samples, data from this study could be applied as neonatal screening reference values for full-term breastfed newborns in relation to their birth weight.

The establishment of expanded newborn screening (NBS) not only results in the early diagnosis and treatment of neonates with inborn errors of intermediary metabolism disorders (IEMDs) but also helps the affected females to reach the reproductive age under medical and dietetic support, as well as to give birth to normal infants. In this review, we aimed to focus on laboratory investigation tests, dietetic management and medical support for most known IEMD pregnant and lactating women, such as those suffering from aminoacidopathies, carbohydrate metabolic diseases and fatty acid (FAO) oxidation disorders.

Objectives: Recently, new criteria for sensitive and specific clinical diagnosis of progressive supranuclear palsy (PSP) have been addressed while distinct clinical phenotypes of the disorder have been increasingly described in the literature. This study aimed to describe past and present aspects of the disease as well as to highlight the cognitive and behavioral profile of PSP patients in relation to the underlying pathology, genetics and treatment procedures.Methods: A Medline and Scopus search was performed to identify articles published on this topic. Articles published solely in English were considered.Results: The most common clinical characteristics of PSP included early postural instability and falls, vertical supranuclear gaze palsy, parkinsonism with poor response to levodopa and pseudobulbar palsy. Frontal dysfunction and verbal fluency deficits were the most distinct cognitive impairments in PSP while memory, visuospatial and social cognition could also be affected. Apathy and impulsivity were also present in PSP patients and had significant impact on relatives and caregivers.Conclusions: PSP is a neurodegenerative disorder with prominent tau neuropathology. Movement, motivation and communication impairments in patients with PSP may limit participation in everyday living activities. Comprehensive neuropsychological assessments are of significant importance for PSP cognitive evaluation. Pharmacologic and non-pharmacologic approaches could be applied in order to relieve patients and improve quality of life.Clinical Implications: Executive dysfunction is the most notable cognitive impairment and dominates the neuropsychological profile of patients with PSP.

Very recently, it was reported that a patient with classical galactosemia and a very high intelligence quotient (IQ) score obtained a university degree. In the present study, two siblings with classical galactosemia (homozygous for Q188R mutation) received upper normal IQ scores when tested with psychometric tools. Additionally, the same IQ scores were determined in their healthy brother when tested at the same age. It was concluded that patients could achieve upper normal IQ scores when on diet and followed up closely. Family and especially maternal care may ameliorate the psychomotor development.

Background: Phenylketonuria (PKU) is a metabolic disorder of phenylalanine (phe) metabolism caused by the liver enzyme phe hydroxylase deficiency resulting in mental retardation. The only treatment for this disorder is the lifelong restriction of natural protein supplemented with phe-free amino acid formula. The aim of this study was to demonstrate the beneficial effect of psychological support in relation to the educational status on mothers with PKU children, who suffered from social discrimination (SD) and damage of quality of life (QLD). Methods: A total number of 42 mothers with PKU children with a mean age of 26.8 years took part in this study. According to their educational status, they were divided into three groups: group a, primary school (n=13); group b, high school (n=15) and group c, university degree (n=14). Psychological support was given once per week for 1 year. Results: University degree mothers achieved the best results in ameliorating their symptoms and signs. Mothers who had completed high school felt a moderate amelioration of their SD and QL, whereas those who had finished primary school only felt a mild reduction of their symptoms. Educational status of the affected mothers should be always taken into account for the classification of the affected mothers into therapeutic groups. Familial and professional environment are very important for the success of psychological support. Conclusions: Overall, the psychological support related to symptoms and signs of this metabolic disorder is in comparison with that in diabetic patients.

Background: Phenylketonuria (PKU) is a metabolic disorder resulting in high phenylalanine (Phe) blood concentrations due to the deficiency of the hepatic enzyme Phe hydroxylase. High Phe levels are currently treated with diet, thus avoiding mental retardation, psychomotor delay, etc. The aim of this study was to find out the self-presentation of the disease by the patients. Methods: A total number of 110 patients self-represented their disease: food allergy (Phe allergy) n=34/110 (30.9%), health problems n=31/110 (28.2%), severe health problems n = 26/110 (23.6%), very severe health problems n =19/110 (17.3%). The Wechsler Intelligence Scale for Children (WISC III) psychometric test was utilized for the evaluation of IQ scores of each participant. A special questionnaire was used focusing on quality of life (QL), social discrimination (SD) and anxiety or depression (AD). Results: IQ scores were found to be higher in food allergy self-represented patients than those of the other tested groups. The lowest IQ scores were observed in those who represented very severe disease. QL, SD and AD were not observed in the food allergy groups. On the contrary, those who self-presented as very severe diseased patients felt high a disturbance of QL, SD and AD. Conclusions: The food allergy group seemed to be a very clever excuse for adhering to PKU treatment resulting in high IQ scores and absence of the mentioned upsets. In contrast, in the other groups of patients' IQ scores were found to be lower than that of food allergy group. Damage of QL, SD, AD were also apparent.

Abstract Background Phenylketonuria (PKU) is an inherited metabolic disorder characterized by high levels of phenylalanine in the blood and brain, resulting in mental retardation, etc. Dietary treatment with low phenylalanine is the common treatment for this disease. Patients with other metabolic disorders, such as diabetes mellitus, were reported to have a higher percentage of quality-of-life damage (QLD) and social discriminations (SDs). Methods To evaluate the degree (%) of maternal QLD and SD in relation to their educational status and place of living during the participation of their PKU children in public events, 110 mothers of PKU children with an average age of 25.7 years took part in this study. We evaluated their QLD and SD according to their educational status (primary school, high school and university) and place of living (small town ≤300,000, city >300,000 inhabitants). A control group was not needed. Special questions (checklist) were created to evaluate the QLD and SD of the mothers of children under dietary control. Cronbach’s α test was used for the measurement of the function of the items in the checklists. Results The covariance between the item pairs and the variance of the total score were calculated. Mothers who had completed primary school and lived in a city with a population >300,000 experienced the highest degree of QLD. In contrast, mothers with a university degree experienced the lowest SD. Overall, the highest SD was observed in mothers who lived in a small town. The affected group of mothers should be psychologically supported.

Objective Cystic fibrosis (CF) is a multisystemic inherited disease. The aim of this study was to determine free carnitine (FC) and acylcarnitine concentrations in CF newborns with various mutations of the CFTR gene perinatally. Study Design FC/acylcarnitines were determined in dried blood spots via liquid chromatography-tandem mass spectrometry (LC-MS/MS) on the third day of life of full-term normal ( n =50) and CF ( n =28) newborns. For infants with elevated immunoreactive trypsinogen values, FC/acylcarnitines were quantified again 48hours later, followed by mutational analysis of CFTR gene via Sanger sequencing. Results Initial FC and sums of acylcarnitine concentrations were statistically significantly lower in CF patients than in controls and even lower 48hours later. The mutations F508del and 621+1G>T were predominantly identified among CF patients. Conclusion Low FC and acylcarnitine concentrations were measured perinatally in CF patients, for all CFTR mutations detected. Carnitine supplementation of breastfeeding mothers could be beneficial.

Background: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. Methods: A cross sectional questionnaire (survey monkey (R)) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. Results: Weaning started at 17-26 weeks in 85% (n=81/95) of centres, > 26 weeks in 12% (n=11/95) and < 17 weeks in 3% (n=3/95). Infant's showing an interest in solid foods, and their age, were important determinant factors influencing weaning commencement. 51% (n=48/95) of centres introduced Phe containing foods at 17-26 weeks and 48% (n=46/95) at > 26 weeks. First solids were mainly low Phe vegetables (59%, n=56/95) and fruit (34%, n=32/95). A Phe exchange system to allocate dietary Phe was used by 52% (n=49/95) of centres predominantly from Northern and Southern Europe and 48% (n=46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods. A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n=39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n=35/95) at infant age > 1y mainly from Southern Europe. 53% (n=50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. Conclusions: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.

Breastfeeding replacement is the only treatment for galactosemia (GAL) and phenylketonuria (PKU) during infancy. We aimed to evaluate the stress degree in mothers who were obliged to replace breastfeeding with special formulas as the only treatment for the diseased newborns. Thirty-two mothers with GAL newborns, 19 on breastfeeding only and 13 on breastfeeding plus formula, participated in this study. Additionally, 54 mothers with PKU infants, 32 offered breastfeeding only and 22 breastfeeding plus formula, participated in the study. Stress degree was evaluated in both groups: GAL and PKU. Mothers on breastfeeding only experienced the highest degree of stress than those who were on breastfeeding plus formula. After 1 month of psychological support, most mothers were ameliorated: mothers on breastfeeding only felt better as compared to those on breastfeeding plus formula. Conversely, in mothers on breastfeeding plus formulas, symptoms and signs of stress almost disappeared. In conclusion, GAL or PKU mothers with breastfeeding only experienced the highest degree of stress when asked for breastfeeding replacement. Psychological support made all the studied groups to feel better or free of symptoms and signs of stress.

Newborn screening is a public health tool for the early diagnoses and treatment of asymptomatic infants with inborn errors of metabolism. Biomarkers and enzyme activities are measured in dried blood spots (DBS) on Guthrie carts to diagnose diseases, which may later appear such as mental retardation and or other disorders could be presented. To evaluate the percentage and the educational status of mothers who do not respond to the requested for a second DBS of a suspected for a disease newborn. We created a questioner about the educational status as well as the etiology of maternal lack of response for a second blood sample. Most of mothers who denied to respond were of low educational status and or immigrants, not knowing our native or English language. The rest were indifferent and or misunderstood the information letter they reserved. Amelioration of the educational status of mothers and or better cooperation with social workers and or midwives, nurses etc. Translation of the information booklet about National Neonatal Screening Program in to more foreign languages should be necessary.

Parents had already taken information about galactosemia from web medical pages because they were asked for a second blood sample from their infant suspected for the disease. All enzyme types of this disorder are diagnosed by neonatal screening perinatally and treated with a galactose (GAL) free diet. The most frequent information about the disease was mental retardation (100%), eye cataracts (100%) liver dysfunction (90.5%), speech delay (76.1%), hypoglycemia (69.0%), seizures (31.0), etc. Most clinical and laboratory information about galactosemia taken from the Internet was correct for the classical type of the disorder. A differentiation of the galactosemia enzyme types is needed.