Dried Blood Spots in Neonatal Studies: A Computational Analysis for the Role of the Hematocrit Effect.

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.

The relationship between neurotransmission-related amino acid blood concentrations and neuropsychological performance following acute exercise.

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.

Quantitation and evaluation of perinatal medium-chain and long-chain acylcarnitine blood concentrations in 12,000 full-term breastfed newborns.

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.

Perinatal Reduced Blood Concentrations of Free Carnitine and Acylcarnitines in Infants with Cystic Fibrosis.

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 48 hours 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 48 hours 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.

Birth weight related essential, non-essential and conditionally essential amino acid blood concentrations in 12,000 breastfed full-term infants perinatally.

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.

Perinatal free carnitine and short chain acylcarnitine blood concentrations in 12,000 full-term breastfed newborns in relation to their birth weight.

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.

Self-estimation of phenylketonuria patients on therapeutic diet. Psychological support.

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.

Self-estimation of phenylketonuria patients on therapeutic diet. Psychological support.

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.

Birth weight related blood concentrations of the neurotransmission amino acids glutamine plus glutamate, phenylalanine and tyrosine in full-term breastfed infants perinatally.

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.

Nutrition and medical support during pregnancy and lactation in women with inborn errors of intermediary metabolism disorders (IEMDs).

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.

The beneficial effect of psychological support on mothers with PKU children who suffer from social discrimination and damage of quality of life.

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.

The Progressive Supranuclear Palsy: Past and Present Aspects.

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.

The significant role of carnitine and fatty acids during pregnancy, lactation and perinatal period. Nutritional support in specific groups of pregnant women.

BACKGROUND & AIMS: Pregnancy is characterized by a complexity of metabolic processes that may impact fetal health and development. Women's nutrition during pregnancy and lactation is considered important for both mother and infant. This review aims to investigate the significant role of fatty acids and carnitine during pregnancy and lactation in specific groups of pregnant and lactating women. METHODS: The literature was reviewed using relevant data bases (e.g. Pubmed, Scopus, Science Direct) and relevant articles were selected to provide information and data for the text and associated Tables. RESULTS: Dynamic features especially of plasma carnitine profile during pregnancy and lactation, indicate an extraordinarily active participation of carnitine in the intermediary metabolism both in pregnant woman and in neonate and may also have implications for health and disease later in life. Maternal diets rich in trans and saturated fatty acids can lead to impairments in the metabolism and development of the offspring, whereas the consumption of long chain-polyunsaturated fatty acids during pregnancy plays a beneficial physiologic and metabolic role in the health of offspring. CONCLUSIONS: Pregnant women who are underweight, overweight or obese, with gestational diabetes mellitus or diabetes mellitus and those who choose vegan/vegetarian diets or are coming from socially disadvantaged areas, should be nutritionally supported to achieve a higher quality diet during pregnancy and/or lactation.

The phenylketonuria patient: A recent dietetic therapeutic approach.

Phenylalanine hydroxylase (PAH) deficiency, commonly named phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism inherited with an autosomal recessive trait. It is characterized by high blood and cerebral Phe levels, resulting in intellectual disabilities, seizures, etc. Early diagnosis and treatment of the patients prevent major neuro-cognitive deficits. Treatment consists of a lifelong restriction of Phe intake, combined with the supplementation of special medical foods, such as Amino Acid medical food (AA-mf), enriched in tyrosine (Tyr) and other amino acids and nutrients to avoid nutritional deficits. Developmental and neurocognitive outcomes for patients, however, remain suboptimal, especially when adherence to the demanding diet is poor. Additions to treatment include new, more palatable foods, based on Glycomacropeptide that contains limited amounts of Phe, the administration of large neutral amino acids to prevent phenylalanine entry into the brain and tetrahydrobiopterin cofactor capable of increasing residual PAH activity. Moreover, further efforts are underway to develop an oral therapy containing phenylalanine ammonia-lyase. Nutritional support of PKU future mothers (maternal PKU) is also discussed. This review aims to summarize the current literature on new PKU treatment strategies.

The significant role of amino acids during pregnancy: nutritional support.

Background: Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and infant health outcome. Normal fetal growth and development depend on a continuous supply of nutrients via the placenta. The placenta transports, utilizes, produces, and interconverts amino acids (AAs).Findings: Concentrations of both nonessential and essential AAs in maternal plasma decrease in early pregnancy and persist at low concentrations throughout. The decline is greatest for the glucogenic AAs and AAs of the urea cycle. Additionally, there is a large placental utilization of the branched-chain AAs, some of which are transaminated to alpha ketoacids and contribute to placental ammonia production. Both nonessential and essential AAs regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of organisms. Some of the nonessential AAs (e.g. glutamine, glutamate, and arginine) play also important roles in regulating gene expression, cell signaling, antioxidant responses, immunity, and neurological function.Conclusions: Nutritional support during pregnancy is of great interest focusing not only to common pregnancies but also to those with low socioeconomic status, vegan-vegetarian groups, and pregnant women with metabolic disorders, the most known maternal phenylketonuria. The latter is of great interest because phenylalanine must be within the recommended range throughout pregnancy in addition to other nutrients such as vitamin B12, folate, etc. Loss of the adherence to this specific diet results in congenital malformations of the fetus. In addition to the routine laboratory test, quantitation of plasma AAs may be necessary throughout pregnancy.

Phenylketonuric patients represent their disease.

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.

Quantitation of the arginine family amino acids in the blood of full-term infants perinatally in relation to their birth weight.

Background Arginine family amino acids (AFAAs) include glutamine (Gln) plus glutamate (Glu), ornithine (Orn), proline (Pro), citrulline (Cit) and arginine (Arg). We aimed to quantitate these amino acids in the blood of full-term infants in relation to their birth weight (BW) perinatally. Methods Breastfeeding full-term infants (n = 2000, 1000 males, 1000 females) with a BW of 2000-4000 g were divided into four 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 third day of life and analyzed via a liquid chromatography tandem mass spectrometry (LC-MS/MS) protocol. Results Gln plus Glu mean values were found to be statistically significantly different between males and females in all studied groups. The highest values of these amino acids were detected in both males and females in group D. Orn mean values were found to be statistically significantly different between males and females of the same BW in all groups except the last one. The lower mean value was determined in group A, whereas the highest was determined in group D. Cit and Arg mean values were determined to be almost similar in all studied groups. Conclusions Gln plus Glu and Orn blood concentrations were directly related to infants' BW. Conversely, Cit and Arg did not vary significantly in all groups.

Replacement of breastfeeding with medical food for the treatment of galactosemia and phenylketonuria: maternal stress.

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.

The significant role of educational status in PKU patients: the beneficial effect of psychological support in depression.

INTRODUCTION: Classical Phenylketonuria (PKU) is a metabolic disease characterized by high phenylalanine (phe) levels in blood and brain. PKU patients are commonly treated with low phe diet supplemented with amino acid free formula. High Phe levels minimize brain tryptophan concentration, the pressure of serotonin, which is responsible for the appearance of depression symptoms. Both amino acids share the same pathway for entering CNS via BBB. Aimed to determine the effect of psychological support on different education status depressed PKU patients via adherence to their diet. METHODS: PKU patients (n = 110) were divided into groups according to their education status: Primary school, High school, University degree. All patients were tasted with a Patient Health Questionnaire (PHQ-9) standardized for Greek population. Psychological support was performed in every depressed patient ones per two weeks for three successive months under the same conditions. Phe blood levels were measured before psychological support and every 15-20 days till the end of the study. RESULTS: Only 2/110 (1.8%) participance had finished Primary school and were healthy. 72/110 (65.5%) High School, out of them 29 were depressed and 36/110 (32.7%) achieved a University degree, only 6 suffered from depression. High phe blood levels were measured in the depressed patients, which dropped near to normal after the end of their psychological support. Referring to depression symptoms, all participance except one presented amelioration of their mood. CONCLUSIONS: Psychological support is beneficial on depressed PKU patients graduated with High School or University degree via adherence to their special diet.

Classical galactosemia patients can achieve high IQ scores.

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.