Functional characterization of a novel missense mutation identified in a Turkish patient affected by severe coagulation factor V deficiency.

Factor V (FV) deficiency is a rare coagulation disorder, characterized by a bleeding phenotype varying from mild to severe. To date, 115 mutations have been described along the gene encoding for FV (F5) but only few of them have been functionally characterized. Aim of this study was the identification and the molecular characterization of genetic defects underlying severe FV deficiency in a 7-month-old Turkish patient. Mutation detection was performed by sequencing the whole F5 coding region, exon-intron boundaries and about 300 bp of the promoter region. Functional analysis of the identified missense mutation was conducted by transient expression of wild-type and mutant FV recombinant molecules in COS-1 cells. Two novel mutations: a missense (Pro132Arg) and a 1-bp deletion (Ile1890TyrfsX19) were identified in the F5 gene. While the frameshift mutation is responsible for the introduction of a premature stop codon, likely triggering F5 mRNA to nonsense-mediated mRNA degradation, the demonstration of the pathogenic role of the Pro132Arg mutation required an experimental validation. Expression experiments showed that the missense mutation causes a significant reduction in FV secretion and in the specific activity of the residual secreted molecule (77% and 78% decrease, respectively). This paper reports the identification of two novel mutations responsible for FV deficiency, thus widening the mutational spectrum of the F5 gene. The Pro132Arg mutation adds to the only other two functionally characterized missense defects in the FV A1 domain.

Screening of blood glucose levels in healthy neonates.

INTRODUCTION: This study aimed to screen the blood glucose levels in healthy term and near-term neonates, and to assess the influence of mode of delivery, birth weight and gestational age on blood glucose levels. METHODS: The blood glucose concentrations of 1,540 healthy term and near-term neonates in the first hour of life were retrospectively evaluated from the clinical charts. Glucose levels were estimated from heel prick capillary samples. The glucose concentration was correlated with the mode of delivery, birth weight and gestational age. RESULTS: Vaginally delivered neonates had higher glucose levels. The glucose concentrations were not significantly different between infants in the different birth weight groups. However, glucose concentration was significantly correlated with gestational age, and the levels were observed to rise with increasing gestational age. CONCLUSION: Screening asymptomatic, healthy term and near-term neonates for hypoglycaemia in the first hour following birth is unnecessary. Glucose strips and glucose meters are useful only as screening devices for neonatal hypoglycaemia, and a screening cut-off value must be established.

Hypernatraemic dehydration in a neonate: brain MRI findings.

Severe hypernatremic dehydration can cause serious neurological complications in neonates. The most significant problems include brain oedema, intracranial haemorrhage, sinus thrombosis, haemorrhagic infarcts and permanent brain damage. The symptoms of many of these complications are similar. With respect to brain MRI findings in hypernatremic neonates, this is a report that describes linear lesions that represent intracranial haemorrhage at the grey-white matter junction. These MRI findings may be helpful for diagnosing hypernatremic dehydration, and for ruling out differential diagnoses for complications of this disorder.

Relationship between small-for-gestational age births and maternal thrombophilic mutations.

Small gestational age (SGA) is one of the major causes of fetal mortality and morbidity. Altered maternal homeostasis as a result of point mutations in the coagulation cascade has been reported as an important risk factor for this adverse pregnancy outcome. This study aims to investigate the relationship between mother's thrombophilic mutations and SGA deliveries in our population. The study group was consisted of sixty-six women who gave birth to one or more SGA babies. 104 women who gave birth to appropriate-for-gestational age (AGA) babies were sampled for the control group. Restriction fragment size analysis were performed by visualizing digested PCR products for Factor V Leiden (G1691A), Factor V Cambridge (A1090G), Factor V A1299G, prothrombin G20210A, methylene tetrahydropholate reductase C677T, A1298C and T1317C mutations. The results of this study indicate that maternal C677T (p=0.01) and A1298C (p<0.01) mutations in MTHFR gene may be suggested as risk factors for SGA outcome in our population. Therefore, maternal screening of these two mutations in the first trimester of pregnancy could help in the assessment of patients.

Complete blood count parameters for healthy, small-for-gestational-age, full-term newborns.

No previous study has investigated the full range of complete blood count (CBC) parameters in small-for-gestational-age (SGA) newborns. The main aim of this study was to compare CBC and peripheral smear parameters in term, healthy SGA neonates and appropriate-for-gestational-age (AGA) neonates, and to establish CBC reference values for full-term SGA newborns. One hundred thirty-two healthy, term newborns (73 SGA and 59 AGA) were included. On day 1, we obtained 109 samples and on day 7 we obtained 77 samples. A CBC and peripheral smear were analyzed for each sample collected and group data were compared. We observed higher mean values for normoblast count, hemoglobin, hematocrit, and red blood cell (RBC) count in the SGA babies than in the AGA babies on day 1. The mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration values for the SGA babies were decreased because of the relatively high RBC count and relatively high mean corpuscular volume we observed in this group. Of the SGA newborns, 21.9% had neutropenia and 4.7% had absolute neutrophil counts lower than 1500/microl on day 1. On both day 1 and day 7, the SGA newborns had higher mean absolute metamyelocyte counts and higher mean I : T (immature : total neutrophil ratio) values than the AGA group. The SGA babies had a lower mean absolute lymphocyte count on day 7 than the AGA group. We detected thrombocytopenia in almost one-third of the 64 SGA newborns tested on day 1. In summary, our study clearly demonstrates that CBC parameters for healthy, full-term, SGA newborns are different from those of healthy, term AGA newborns. This is the first study that has documented different mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, metamyelocyte counts, lymphocyte counts, and I : T in SGA babies compared with AGA babies.

Captopril-induced pancytopenia in a premature newborn.

A preterm infant with renovascular hypertension who developed significant trilineage bone marrow suppression after receiving captopril is reported. Captopril-associated pancytopenia is a very rare complication that was thought to be dose-related and usually caused by accumulation of the drug through defective renal tubular excretion. In our patient, it appears that the combination of renal artery stenosis and renal tubular dysfunction of prematurity might have led to pancytopenia. Captopril should be used with caution especially in premature babies and newborns with underlying renal or renovascular disease even if they do not have overt renal dysfunction. Monitorization of these babies with creatinine clearance or free serum captopril levels may help to establish accumulation of the drug before causing pancytopenia.

Congenital H-type fistula: delayed diagnosis in a preterm infant.

H-type tracheoesophageal fistula is a rare congenital condition. Its rarity and concurrent problems, such as respiratory distress, may delay its detection. We report delay in the diagnosis in a preterm small-for-gestational-age baby who showed symptoms of apnea and recurrent pneumonia, even when she was being fed by orogastric tube.

Significant differences between capillary and venous complete blood counts in the neonatal period.

The normal capillary and venous hematologic values for neonates have not been defined clearly. It is well known that capillary blood has higher hemoglobin (Hb) and hematocrit (Hct) values than venous blood. In a recent study, we reported differences between capillary and venous complete blood counts (CBC) in healthy term neonates on day 1 of life. The aim of this study was to extend our previous investigation. Term neonates (n=141) were stratified into four groups by days of postnatal age: group 2 (day 7, n=38), group 3 (day 14, n=35), group 4 (day 21, n=32) and, group 5 (day 28, n=36). Data from our previous study were included in the statistical analysis as group 1 (day 1, n=95). A CBC and differential count were carried out on each capillary and venous sample drawn simultaneously. Within each group, the mean and standard deviation for each parameter in capillary and venous blood were calculated and then compared using the paired sample t-test. In all groups, the capillary blood samples had higher Hb, Hct, red blood cell (RBC), white blood cell (WBC), and lymphocyte counts. In each group, venous platelet counts were significantly higher than the corresponding capillary values. There was also a trend toward higher venous mean corpuscular volume, higher capillary polymorphonuclear leukocyte (PML) count and mean platelet volume in all groups. In both capillary and venous blood, Hb, Hct, RBC, MCV values and WBC, lymphocyte, PML counts decreased and platelet counts increased steadily during neonatal period. This study reveals that CBC parameters and differential counts may differ depending on the blood sampling used. The findings underline the importance of considering the sample source when using hematologic reference ranges for healthy or septic neonates. When interpreting results, the term 'peripheral blood' should be replaced with 'capillary blood' or 'venous blood' so that an accurate assessment can be made.

Bone marrow failure with concurrent enteroviral infection in a newborn.

A newborn baby, with transient pancytopenia concurrent to Echovirus type 11 infection, was hospitalized for fever, diarrhea, rash, generalized petechiae and hepatosplenomegaly. Subsequent investigation showed bone marrow failure. To our knowledge this is the first reported case of bone marrow failure with concomitant enteroviral infection.

Popliteal pterygium associated with neonatal Marfan syndrome: case report.

This report describes the case of a male infant with neonatal Marfan syndrome who also exhibited popliteal pterygia. The patient's father had classic Marfan syndrome. The differential diagnosis in the neonatal case included congenital contractural arachnodactyly (Beals syndrome) and various forms of popliteal pterygium syndrome. We note the diagnostic features of the case, discuss the novel finding of pterygia in association with neonatal Marfan syndrome, and highlight the possible role of collagen defects in the pathogenesis of limb pterygia.

Occurrence of an aortic arch anomaly in two siblings born to a diabetic mother.

A patient with interruption of aortic arch type A, born to a diabetic mother, is described. The patient, a male infant, was the fourth child of a 29-year-old mother, and had a sibling with coarctation of the aorta. The mother had been treated for insulin-dependent diabetes mellitus for the previous 10 years. The infant died on the 3rd day of life after symptoms of cardiogenic shock. To our knowledge, interruption of aortic arch type A has not been previously described in infants of diabetic mothers. The relevance of the case is discussed and the literature reviewed.

Intranasal budesonide spray as an adjunct to oral antibiotic therapy for acute sinusitis in children.

We investigated the clinical value of intranasal budesonide in acute sinusitis in 52 children with acute maxillary sinusitis. We randomly divided them into two groups: group 1 received oral pseudoephedrine (2 x 30 mg) and cefaclor (40 mg/kg) for 10 days, and group 2 received intranasal budesonide (2 x 100 microg) and cefaclor (40 mg/kg) for 10 days. Symptoms of headache, cough, and nasal stuffiness and signs of nasal discharge were graded before and after treatment. The patients whose symptoms and signs completely normalized after treatment were considered to have recovered, and those with persisting symptoms and signs after treatment as having not recovered. The results of the two treatment groups were compared. The recovery rate of the children in group 2 were significantly higher than those in group 1 (P < 0.05). No adverse drug effects were determined during the study period. These findings suggest that topical steroids may be a useful adjunctive agent in the treatment of acute sinusitis of children without apparent side effects and can possibly hasten the resolution of symptoms.

Subcutaneous fat necrosis of the newborn associated with anemia.

Subcutaneous fat necrosis (SFN) of the newborn characteristically affects full-term infants who have experienced perinatal distress, such as hypothermia, obstetric trauma, or asphyxia. We report a newborn who had pallor, deep breathing, and severe anemia immediately after birth. She developed SFN on the fourth postnatal day. Her condition improved after blood transfusions and the skin lesions resolved in 6 weeks. This appears to be the first report of SFN associated with anemia.

Fatal acidosis in a neonate with Pearson syndrome.

We report a neonate who presented with hypotonia, hypoglycemia, and severe lactic acidosis. The patient's acidosis did not respond to bicarbonate replacement and dialysis. Postmortem liver samples revealed portal dilatation, fibrosis, canalicular proliferation, cholestasis, and hepatocellular hemosiderosis. Vacuolization of bone marrow precursors suggested a diagnosis of Pearson syndrome. A common mitochondrial DNA deletion of 4,978 bp was found. We emphasize that Pearson syndrome should be considered in neonates with lactic acidosis despite absence of anemia.

Alpha-2-macroglobulin levels in early respiratory distress syndrome.

The vasoactive products of uncontrolled protease activity can play an important role in the pathogenesis of respiratory distress syndrome in newborn infants. In this study alpha-2-macroglobulin, which has antiproteolytic activity, was studied in the first few hours of life in preterm infants with and without respiratory distress syndrome. Mean plasma alpha-2-macroglobulin levels were found to be similar in both groups. These findings implicated that alpha-2-macroglobulin has no significant role in the pathogenesis of respiratory distress syndrome.

Relationship between maternal and neonatal iron stores.

In this study, hemoglobin (Hb), mean corpuscular volume (MCV) and serum ferritin (SF) levels were measured in 76 neonates and their mothers at delivery. Infants were grouped according to their gestational ages. Group I (< 34 weeks), group II (34-37 weeks) and group III (> 37 weeks) consisted of 15, 33 and 28 infants, respectively. Blood studies were repeated at two months of age in 50 neonates (26 from group II and 24 from group III). Among the three groups of infants, SF levels were lowest in group I, and among mothers, Group III had the lowest levels. There were positive correlations between maternal and neonatal SF levels in groups II and III. There was no difference between the SF levels of neonates born to mothers with depleted or adequate iron stores. Anemia with a normal SF level was present in 14.4 percent, subclinic iron deficiency (normal Hb and low SF level) in 11 percent and iron deficiency anemia (low Hb and low SF levels) in 7.8 percent of the mothers. At two months of age 38.4 percent of preterm and 16.6 percent of term infants had Hb concentrations less than 10 g/dl. Only one of these infants had a low SF level. There was a negative correlation between maternal SF levels and the Hb concentration of term infants at two months of age.