Kleopatra H Schulpis

Aghia Sophia Children’s Hospital, Athínai, Attica, Greece

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Publications (170)397.43 Total impact

  • No preview · Article · Dec 2015
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    ABSTRACT: Hawkinsinuria is a rare inborn error of tyrosine metabolism. To study novel hawkinsinuria cases by monitoring their biochemical profile and conducting a mutation analysis. Among 92,519 newborns that underwent expanded newborn screening, two unrelated cases with high tyrosine blood levels were further investigated by chromatographic techniques and via genetic testing for 4-hydroxyphenylpyruvate dioxygenase (HPD) gene. Elevated levels were monitored for blood/plasma tyrosine and for the specific diagnostic markers in urine. The two newborns were put on a special low tyrosine diet. Till completion of the 1st year of their life, liver function tests and brain MRI were normal. The mutation A33T was identified in both cases, while one neonate carried an additional novel mutation of HPD gene (V212M). Two mutations of HPD gene, A33T, which are associated with hawkinsinuria and a novel one (V212M) were detected for the 1st time in Greek newborns.
    No preview · Article · Jul 2015
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    ABSTRACT: A 23-mutation panel for CFTR carrier screening is recommended to women of reproductive age by the American College of Obstetricians and Gynecologists. In the present study the optimized efficiency regarding the carrier rate of Next-Generation sequencing (NGS) technology is compared to the one of limited mutation detection panels. A total of 824 consequent cases were subjected to the commercial Cystic Fibrosis Genotyping Assay. Some 188 negative samples randomly selected from the initial group of probands were further subjected to an extended mutation panel characterized by 92% detection rate, as well as to massive parallel sequencing. Twenty-two probands subjected to the commercial assay proved to carry one mutation included in the ACOG panel (carrier rate 0.0267). The latter panels revealed the presence of mutations not included in the ACOG panel in four probands, resulting to an increase of carrier rate of 0.0106 in the case of in-house panel and an increase of rate of 0.0213 if NGS was used. The above data seem to support the implementation of NGS in the routine CFTR carrier screening.
    No preview · Article · Apr 2015 · Scandinavian journal of clinical and laboratory investigation
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    ABSTRACT: Background: Variants of fat mass and obesity associated gene (FTO) and melanocortin-4 receptor gene (MC4R) are related to obesity, overweight and type 2 diabetes. Objectives: To examine the presence of FTO and MC4R variants in Greek newborns. Subjects and methods: A total 1530 newborns of Greek origin were subjected to genetic testing for rs9939609 (FTO) and for rs17782313 (MC4R) variants using dried blood spot (DBS) analysis. Results: Some 20.2% of newborns carried none of the tested variants. FTO homozygotes and FTO heterozygotes correspond to 18.0% and 45.9% of neonates, respectively. MC4R homozygotes and MC4R heterozygotes were identified in 6.7% and 36.3% of neonates, respectively. Of the infants, 2.2% carried both variants in homozygosity, whereas heterozygotes for both variants correspond to 16.7% of the tested neonates. Conclusion: The results indicate high prevalence of homozygosity and heterozygosity for tested variants. Early screening via DBS may be beneficial in order to adopt a healthy lifestyle.
    No preview · Article · Dec 2014 · Journal of pediatric endocrinology & metabolism: JPEM
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    ABSTRACT: Background: There is evidence in support of low bone density in young patients with disorders of phenylalanine metabolism; however, little is known about muscle and fat mass in these patients, especially in those with mild hyperphenylalaninemia (mHPA). Objectives: We aimed to evaluate body composition of children and adolescents with early-diagnosed disorders of phenylalanine metabolism. Patients and Methods: The study was conducted in the Institute of Child Health, which is the national center that performs newborn screening. Bone, muscle, and fat mass of 48 patients with phenylketonuria (PKU) and 32 patients with mild mHPA, aged five to 18 years, were compared to 57 age- and sex-matched controls. Dual energy X-ray absorptiometry was used for this purpose. Results: Compared to controls, bone mineral density (BMD) was lower in patients with PKU (mean total body BMD z score, 0.11; P = 0.03) and in those with mild mHPA (mean lumbar BMD z score, -0.34; P = 0.01). Lean body mass and fat mass were not significantly affected in the study group. Comparison between the two patients groups did not reveal any difference in body composition profiles; however, pubertal status appeared important for within-group comparisons. Fat mass was significantly increased in teenagers with PKU, which was more evident in those with poor dietary compliance irrespective of gender (fat mass z score, 0.66; P = 0.018). Finally, positive correlations were found not only between bone, muscle, and fat mass in both groups, but also between fat mass and Phenylalanine levels in patients with PKU (r, 0.46; P = 0.001). Conclusions: Bone mineral density appears suboptimal in young patients with disorders of phenylalanine metabolism. Adolescents seemed more prone to obesity, especially when their dietary adherence was poor, whereas muscle mass was not considerably affected. To ensure healthier bones and less fat content, close follow-up as well as proper lifestyle advice is needed.
    Full-text · Article · Jul 2014 · International Journal of Endocrinology and Metabolism
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    ABSTRACT: Glucose-6-Phosphate Dehydrogenase (G6PD) gene is located at the X-chromosome at Xq28 and the disease is recessively inherited predominantly in males. More than 400 variants have been proposed based on clinical and enzymatic studies. The aim of the current study was to identify C563T mutation in G6PD-deficient newborns and to correlate the enzyme residual activity with the presence of the mutation. Some 1189 full-term neonates aged 3-5 days old were tested for G6PD activity in dried blood spots from Guthrie cards using a commercial kit. DNA extraction from Guthrie cards and mutation identification among the deficient samples were performed with current techniques. A total of 92 (7.7%) newborns were G6PD-deficient. In 46 (50%), the mutation C563T was identified. The residual activity in C563T hemizygote males (n = 28) was statistically significantly lower (1.23 ± 0.93 U/g Hb) than that in non-C563T G6PD-deficient males (n = 25) (4.01 ± 1.20 U/g Hb, p < 0.0001) and in controls (13.6 ± 2.9 U/g Hb, p < 0.0001). In C563T heterozygote females, the estimated enzyme activity was lower than that determined in non-C563T females. Male C563T hemizygotes suffer from G6PD deficiency and severe neonatal jaundice. G6PD activity showed statistically significant correlation with total bilirubin blood levels.
    No preview · Article · Jan 2014 · Scandinavian journal of clinical and laboratory investigation
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    ABSTRACT: Aim: Body composition evaluation in patients with galactosemia and its variants. Methods: The body composition of young subjects with galactose metabolic disorders was analyzed with dual X-ray absorptiometry. The subjects were divided into the classic galactosemia (CG; n=14) group and the group with other galactose metabolic disorders (OGMD, e.g., epimerase deficiency; n=8). Results: In both groups, bone strength and bone mineral density Z-scores were normal. However, CG patients appeared sarcopenic (median muscle mass Z-score=-1.93), whereas OGMD subjects had low-normal muscle mass. In addition, approximately half of all patients were overweight. In CG patients, bone mass was strongly correlated to muscle mass (r=0.81), whereas in OGMD patients it was positively correlated to body mass index (r=0.78). Conclusions: An imbalance between muscle and fat mass, especially in patients with classic galactosemia, was observed. Given the observed strong correlation between bone and muscle mass, more effective lifestyle counseling is needed.
    No preview · Article · Sep 2013 · Journal of pediatric endocrinology & metabolism: JPEM
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    ABSTRACT: Hyperphenylalaninemia (HPA) leads to increased oxidative stress in patients with phenylketonuria (PKU) and in animal models of PKU. Early diagnosis and immediate adherence to a phenylalanine-restricted diet prevents HPA and, consequently, severe brain damage. However, treated adolescent and adult PKU patients have difficulties complying with the diet, leading to an oscillation of phenylalanine levels and associated oxidative stress. The brain is especially susceptible to reactive species, and oxidative stress might add to the impaired cognitive function found in these patients. The restricted PKU diet has a very limited nutrient content from natural foods and almost no animal protein, which reduces the intake of important compounds. These specific compounds can act as scavengers of reactive species and can be co-factors of antioxidant enzymes. Supplementation with nutrients, vitamins, and tetrahydropterin has given quite promising results in patients and animal models. Antioxidant supplementation has been studied in HPA, however there is no consensus about its always beneficial effects. In this way, regular exercise could be a beneficial addition on antioxidant status in PKU patients. A deeper understanding of PKU molecular biochemistry, and genetics, as well as the need for improved targeted treatment options, could lead to the development of new therapeutic strategies.
    Full-text · Article · May 2013 · Metabolic Brain Disease
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    ABSTRACT: Biotinidase deficiency (BTD) is an inherited disorder with severe clinical manifestations if not treated early. 63119 neonates were tested for BTD according to a 3-step protocol. Biotinidase activity was initially estimated through standard colorimetric method on dried blood spots, then the suspected samples were subjected to molecular analysis of the BT gene and determination of BT activity in serum through an HPLC method. 14 infants with partial BTD (incidence 1:4508) were detected. Nine of them were homozygotes (D444H/D444H), and 4 compound heterozygotes carrying D444H combined with Q456H, T532M, C186Y and R157H, respectively. All were asymptomatic and supplemented with 10mg biotin. Although the number of screened neonates is rather small, it may be suggested that the incidence of the partial BTD infants is the highest ever reported. Detection of BTD should be added to the Greek national neonatal screening program.
    No preview · Article · Apr 2013 · Gene

  • No preview · Article · Mar 2013
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    ABSTRACT: Replacement of natural protein intake, low total antioxidant status (TAS) and DNA oxidation and high phenylalanine (Phe) blood levels are implicated with poorly controlled patients with PKU. In this study we aimed to investigate the effect of diet on the main Protein Energy Wasting (PEW) along with other metabolic parameters in patients with phenylketonuria (PKU). Twenty-four poorly controlled patients (group A) and thirty patients who strictly adhered to their diet (group B) as well as controls (n=50) underwent laboratory tests: complete blood count, concentrations of ferritin, lipid, lipoprotein, TAS, as well as Phe levels with appropriate methodology. Phe levels differed significantly among the groups. Lipids lipoproteins, except HDL, were higher in group A than those measured in group B and controls. TG was not higher in any group. TAS (386 ± 30 vs 204 ± 23 μmol/L, p < 0.001), ferritin (65 ± 12 vs 52 ± 10 μg/L, p < 0.01) were significantly higher in group B. In contrast, White Blood Cell count (WBC) (6.1 ± 1.0 vs 8.3 ± 1.2 × 10-3/μL, p < 0.01), the absolute number (1.9 ± 0.6 vs 2.9 ± 0.7 × 10-3/μL, p < 0.001) and percentage of lymphocytes (18.5 ± 3.0 vs 39.3 ± 4.0%, p < 0.01) were lower in group A than those in group B, whereas total protein and albumin levels were similar among the groups. Most main PEW biomarkers, the low WBC, the low absolute and percentage of lymphocytes in poorly controlled patients may be directly and/or indirectly affected by their high Phe levels and/or low TAS levels in children with PKU on loose diet.
    No preview · Article · Jan 2013 · Journal of Pediatric Biochemistry
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    ABSTRACT: Phenylketonuria (PKU) therapeutic diet is characterized by the great replacement of natural protein with a phenylalanine-free formula. To investigate the effect of diet on the amino acid serum levels in PKU patients and their total antioxidant status (TAS). Thirty-seven poorly controlled patients (group A), 43 patients who strictly adhered to their diet (group B) and 50 controls were included in the study. In patients and controls blood chemistry, TAS and serum amino acid level determinations were performed. Phenylalanine levels significantly differed among the groups. Glutamine and ornithine levels were significantly higher in group A, while TAS (416±30 vs 228±23μmol/L, p<0.001), citrulline (39±15 vs 26±5μmol/L, p<0.001) and arginine levels (61±11 vs 80±12μmol/L, p<0.001) were higher in group B. The other determined amino acid serum levels did not differ among the groups of patients and controls. The high glutamine and ornithine levels in group A may reflect the high natural protein intake. High phenylalanine levels in these patients may locally affect the hepatocyte, enterocyte, and/or renal function resulting in low citrulline and arginine levels contributing to their low TAS.
    Preview · Article · Jul 2011 · Clinical biochemistry

  • No preview · Article · Feb 2011 · Clinical Chemistry and Laboratory Medicine
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    ABSTRACT: To investigate the effect of the mode of delivery on maternal-neonatal Mg and Zn levels. Two groups of pregnant women participated in the study: Group A (n = 16) with normal labor and vaginal delivery and group B (n = 14) with scheduled cesarean section (CS). Blood was obtained at the beginning of the labor, immediately after delivery and from the umbilical cord (CB). Serum Mg and Zn were measured with atomic absorption spectroscopy and total antioxidant status (TAS) levels with a chemical autoanalyser. Mg, Zn and TAS levels were similar pre-delivery in both groups. TAS levels, Mg (0.81 ± 0.09 vs 0.69 ± 0.03 mmol/L, p < 0.001) and Zn levels (9.34 ± 0.37 vs 5.74 ± 0.24 μmol/L, p < 0.001) were significantly decreased after vaginal delivery. These biochemical parameters were measured practically unaltered at the same times of study in group B. The mineral levels did not differ in the CB of both groups. The decreased maternal Mg, Zn and TAS levels post vaginal delivery may be due to the participation of skeletal and uterus muscles and the similar levels of the minerals in the CB of neonates to the placental protection.
    No preview · Article · Nov 2010 · Scandinavian journal of clinical and laboratory investigation
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    ABSTRACT: Thyroid hormones (THs) exert a broad spectrum of effects on the central nervous system (CNS). Hypothyroidism, especially during CNS development, can lead to structural and functional changes (mostly resulting in mental retardation). The hippocampus is considered as one of the most important CNS structures, while the investigation and understanding of its direct and indirect interactions with the THs could provide crucial information on the neurobiological basis of the (frequently-faced in clinical practice) hypothyroidism-induced mental retardation and neurobehavioral dysfunction. THs-deficiency during the fetal and/or the neonatal period produces deleterious effects for neural growth and development (such as reduced synaptic connectivity, delayed myelination, disturbed neuronal migration, deranged axonal projections, decreased synaptogenesis and alterations in neurotransmitters' levels). On the other hand, the adult-onset thyroid dysfunction is usually associated with neurological and behavioural abnormalities. In both cases, genomic and proteomic changes seem to occur. The aim of this review is to provide an up-to-date synopsis of the available knowledge regarding the aforementioned alterations that take place in the hippocampus due to fetal-, neonatal- or adult-onset hypothyroidism.
    No preview · Article · Oct 2010 · Metabolic Brain Disease
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    ABSTRACT: To investigate the effect of diet on total antioxidative status (TAS), transferrin, ferritin and ceruloplasmin serum levels in phenylketonuric (PKU) children. Seventeen poorly controlled PKU children underwent clinical and laboratory examinations before, 'off diet', and 60 days after adhering to their special diet 'on diet', whereas controls (N = 24) were examined once. Blood chemistry was performed with the appropriate methodologies. Phenylalanine levels differed significantly among the examined groups. Lipids and lipoproteins were higher in 'off diet' than in 'on diet' group, except of high density lipoprotein and apolipoprotein AI that remained unaffected. Total antioxidative status (386 ± 30 vs 204 ± 23 μmol/L, p < 0.001), ferritin (48.2 ± 2.3 vs 33.0 ± 2.8 μg/L, p < 0.001) and ceruloplasmin (40.02 ± 2.5 vs 25.5 ± 2.8 mg/dL, p < 0.001) levels were significantly higher in 'on diet' patients' group compared to 'off diet' one. The low lipoprotein and the high TAS and ferritin levels in patients with PKU 'on diet' may be related to the vegetarian diet and the rich in iron formula supplementation. The low ferritin levels found in 'off diet' patients with PKU may be attributed to a decreased liver production of ceruloplasmin, which evaluation may be a useful tool for the follow-up of patients with PKU.
    No preview · Article · Oct 2010 · Acta Paediatrica
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    ABSTRACT: To explore the influence of folate-fortified foods (ready-to-eat [RTE] breakfast cereals or fruit-juice drinks) on the relation between the methylenetetrahydrofolate reductase (MTHFR 677C>T) polymorphism and plasma total homocysteine (tHcy) concentrations in healthy children. This was a cross-sectional study by face-to-face interview. A total of 186 sixth-grade students participated from randomly selected primary schools in Volos, Greece. Fasting plasma tHcy, folate, and vitamin B12 were measured. The MTHFR genotypes were determined. Anthropometric data were collected and dietary intake was assessed by two non-consecutive 24-h recalls. Participants were characterized as non-consumers of RTE breakfast cereals or fruit-juice drinks if there was no report of any such food during the 24-h recall interviews; all other children were classified as consumers. Geometric means for plasma tHcy were higher, whereas plasma folate was lower in non-consumers compared with consumers. The sample was divided by consumption status (yes or no) to explore the significance of each polymorphism depending on consumption status. The association between the genotype and tHcy was restricted to non-consumers (P<0.05). Specifically, only in children who did not consume RTE breakfast cereals or fruit-juice drinks did the TT genotype carriers exhibit higher tHcy concentrations when compared with C-allele carriers (P<0.05). In contrast, in consumers, circulating tHcy was similar regardless of genotype. These observational findings support a beneficial effect of RTE breakfast cereals and fruit-juice drinks on lowering plasma tHcy and improving folate status in children. Also, consumption of folate-fortified foods modulates the association of the MTHFR 677C>T polymorphism with tHcy, suggesting that habitual consumption of folate-fortified foods is a practical approach in providing consistent protection to those children who may benefit the most, i.e., carriers of the TT genotype.
    No preview · Article · Oct 2010 · Nutrition
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    ABSTRACT: To investigate erythrocyte membrane AChE, Na(+), K(+)-ATPase and Mg(2+)-ATPase activities in mothers and their full-term or premature newborns in relation to the mode of delivery. Blood was obtained from mothers pre- and post-delivery and the umbilical cord (CB) of their full-term newborns: Group A₁ (n = 16) born with vaginal delivery (VD), Group B₁ (n = 14) full-terms with scheduled cesarean section (CS), Group A₂ (n = 12) prematures with VD, Group B₂ (n = 14) prematures with CS. Total Antioxidant Status (TAS) and common laboratory tests were measured with routine methods, and the membrane enzyme activities spectrophotometrically. TAS was reduced in mothers post VD and in the CB whereas remained unaltered in CS mothers and their newborns. AChE and Na(+), K(+)-ATPase were increased in mothers post VD. AChE was lower in the CB of prematures than that of full-terms independently of the mode of delivery. Na(+), K(+)-ATPase activity was increased in the groups of mothers post VD and decreased in prematures. The enzyme was higher in prematures with CS than that with VD. Mg(2+)-ATPase activity was unchanged. The increased maternal AChE and Na(+), K(+)-ATPase activities may be due to the low TAS determined post VD, whereas their decreased activities in prematures to their immaturity.
    No preview · Article · Oct 2010 · Scandinavian journal of clinical and laboratory investigation

  • No preview · Article · Aug 2010 · Clinical Genetics
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    ABSTRACT: Background & aims Low Zinc (Zn) and Magnesium (Mg) concentrations during pregnancy are implicated with low birth weight, malformations and increased mortality and morbidity. We aimed to compare serum concentrations of Zn and Mg in Greek (N = 219) and immigrant Albanian mothers (N = 230) at delivery and in the cord blood of their neonates. Methods A 60 day's food diary was kept from each mother. Zn and Mg sera concentrations were measured with atomic absorption spectrometry. Results Carbohydrates, total fat and cholesterol intake were significantly higher in Albanian mothers when compared with those of Greek origin. On the contrary, total protein and especially animal protein intake were higher in the Greek mothers. Magnesium intake was similar between the two ethnic groups, whereas Zn intake in Albanian mothers was evaluated lower (5.8 ± 1.4 mg/d) when compared with that of Greeks (10.8 mg ± 1.2 mg/d, p < 0.001). Mg serum concentrations in mothers and newborns were similar (2.08 ± 0.15, 1.98 ± 0.12 vs 1.92 ± 0.13, 1.94 ± 0.14 mg/dl respectively, p > 0.05). In contrast, Zn concentration was significantly lower (49.8 ± 1.2 μg/dl) in the Albanian mothers as compared with that of Greeks (62.2 ± 1.4 μg/dl, p < 0.001). Consequently, Zn concentrations were found lower in Albanian newborns (52.0 ± 1.4 μg/dl) than those of Greek neonates (61.8 ± 1.2 μg/dl, p < 0.001). Conclusion Mg serum concentrations were similar in the studied mothers and their neonates. Zn serum concentrations were significantly lower in Albanian mothers and newborns than those of Greek origin, probably due to the reduced rich in Zn animal protein intake from Albanians. The latter may be the consequence of their low socioeconomic status.
    No preview · Article · Aug 2009 · e-SPEN the European e-Journal of Clinical Nutrition and Metabolism

Publication Stats

2k Citations
397.43 Total Impact Points


  • 1990-2015
    • Aghia Sophia Children’s Hospital
      Athínai, Attica, Greece
  • 2001-2014
    • Institute of Child Health - Greece
      Athínai, Attica, Greece
    • Red Cross Hospital, Athens
      Athínai, Attica, Greece
  • 1995-2009
    • Institute of Child Health
      Athínai, Attica, Greece
  • 2008
    • Red Cross
      Washington, Washington, D.C., United States
  • 2000-2008
    • Institute for Child Health Policy (ICHP)
      Greece, New York, United States
    • National and Kapodistrian University of Athens
      • Division of Experimental Physiology
      Athínai, Attica, Greece
  • 1993-2007
    • Νοσοκομείο Παίδων Η Αγία Σοφία
      Athínai, Attica, Greece
  • 1997
    • A. Sygros Hospital
      Athínai, Attica, Greece