The role of CRP, PCT, IL-6 and presepsin in early diagnosis of bacterial infectious complications in paediatric haemato-oncological patients.

Bacterial infection is the most common complication in paediatric oncological patients during cancer treatment. A suitable tool for early prediction of unfavourable course of infection is still needed. We performed a prospective longitudinal observational study to evaluate of the role of serum biomarkers (C-reactive protein, procalcitonin, interleukin-6, presepsin) in the early diagnosis of bacteraemia (gram-negative versus gram-positive) in patients with haematological malignancies. We observed 69 febrile episodes in 33 patients (17 male, 16 female; 1.5-18.9 years, mean 7.31 years, median 5 years). Within this sample, there were 22 cases of positive blood cultures, 16 cases of sepsis, 38 cases of fever with no signs or symptoms of sepsis, and two deaths from infectious complications. All markers tested had good negative predictive value (73% - 93%). CRP was characterized by good specificity for registration bacteraemia (96%, 95% CI: 85% - 99%), but other results were inconclusive. We identified comparably balanced sensitivity (64% - 81%) and specificity (61% - 88%) for interleukin-6 and procalcitonin, and we proved their quality to predict positive blood culture and clinical signs of sepsis as well. Patients with gram-negative bacteraemia had significantly elevated levels of PCT and IL-6 in comparison with a group of patients with gram-positive bacteraemia (p = 0.04 for PCT and p = 0.005 for IL-6). Presepsin was characterized by poor specificity (27%, 95% CI: 15% - 43%) and positive predictive value (24%, 95% CI: 12 - 39%) for predicting bacteraemia, and by better sensitivity (84%, 95% CI: 55% - 98%) and specificity (58%, 95% CI: 42% - 73%) for predicting clinical signs of sepsis.

GAI - distinct genotype and phenotype characteristics in reported Slovak patients.

OBJECTIVES: The clinical, biochemical and genetic findings in two Slovak patients with glutaric aciduria type I (GAI) are presented. BACKGROUND: GAI is a rare autosomal recessive neuro-metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase, which is involved in the catabolic pathways of lysine, hydroxylysine and tryptophan. This enzymatic defect gives rise to elevated levels of glutaric acid (GA), 3-hydroxyglutaric acid (3-OH-GA) and glutarylcarnitine (C5DC) in body fluids. METHODS: Biochemical and molecular-genetic tests were performed. Urinary organic acids were analysed by Gas Chromatography/Mass Spectrometry (GC/MS) and the entire coding region of the GCDH gene, including flanking parts, was sequenced. RESULTS: We found the presence of typical metabolic profile and novel causal pathogenic variants in both GAI patients. CONCLUSION: We present the first report of two Slovak patients with GAI, which differed in the clinical and biochemical phenotype significantly. They were diagnosed by two distinct approaches - selective and newborn screening. Their diagnosis was complexly confirmed by biochemical and later on molecular-genetic examinations. Though we agreed with a thesis that early diagnostics might positively influenced patient's health outcome, contradictory facts should be considered. Supposed extremely low prevalence of GAI patients in the general population and/or the existence of asymptomatic individuals with a questionable benefit of the applied therapeutic intervention for them lead to doubts whether the inclusion of disease into the newborn screening programme is justified well enough (Tab. 1, Fig. 3, Ref. 41).

Amount of folic acid in different types of nutrition used in the neonatal period.

BACKGROUND: Folic acid is one of the important supplements for adequate development during pregnancy. A higher intake of folic acid during pregnancy and lactation is recommended. METHODS: In prospective study the group of premature newborns (n = 52) and the type of nutrition were observed. The red blood cell (RBC) folate concentration levels were determined in the first 24 hours after delivery, before and after oral treatment with folic acid (100 µg/day). Immunochemical analysis for the determination of folate in erythrocytes was performed. RESULTS: In the group of premature newborns the RBC folate concentration levels after treatment were significantly increased (p < 0.0001). A dynamic increase in the concentration levels of folates in erythrocytes before and after treatment was observed, in spite of the reciprocally decreasing blood count parameters, but without any statistically significant correlation. The infant nutrition before treatment contained significantly higher amount of folic acid in fortified breast milk compared to breast milk (p = 0.04). CONCLUSION: The various types of nutrition for preterm newborns contain a different amount of folic acid. It poses a question of real needs of these patients. The best way to determine the optimal whole amount of folate is to know the real levels of folate in premature newborns (Tab. 2, Fig. 5, Ref. 26). Text in PDF www.elis.sk.

Trisomy 18 mimicking Smith-Lemli-Opitz syndrome in the immediate neonatal period.

The study describes a dysmorphic newborn infant with life-threating anomaly, later diagnosed as trisomy 18, mimicking Smith-Lemli-Opitz syndrome in the immediate neonatal period. The establishment of the correct diagnosis in the first days of life is very important for the decision-making process, because trisomy 18 has a poor prognosis, and treatment is not instituted, whereas cholesterol supplementation may be of benefit to patients with Smith-Lemli-Opitz syndrome. Ultraviolet spectrophotometry showed very easy and rapid method for differentiation of both syndromes, where gas chromatography/mass spectrometry analysis is not available. (Fig. 2, Ref: 18.)

Serum free carnitine in medium chain acyl-CoA dehydrogenase deficiency.

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common disorder of fatty acid beta-oxidation and presents acutely with hypoglycemia, or a Reye-like illness with low free carnitine, often provoked by an infection or an excessive period of fasting. After acute attack these children are for the most time asymptomatic and may have normal plasma free carnitine concentrations. We observed a regularity in time course of serum free carnitine concentration during two attacks of Reye-like illness in patient with MCAD deficiency. Molecular investigation confirmed that the patient was homozygote for A985G mutation. Free carnitine was measured by enzymatic UV-test. First attack of severe hypoglycemia and Reye-like symptoms started at the age of 15 months and the second at the age of 25 months. In both episodes, treatment with intravenous glucose was given immediately, but without carnitine supplementation. Between the attacks patient was on a normal diet. In both attacks, low serum free carnitine concentration from the time of acute attack continually decreased for up to 8-13 days and then normalized at about 25 days after attack. We think that the time course of serum free carnitine may help in knowledge about carnitine depletion in MCAD deficiency. This is the first observation of this pattern during an acute attack and needs to be confirmed by other patients with MCAD deficiency. (Fig. 2, Ref. 7.).

Metabolic cause of Reye-like syndrome.

The most frequent metabolic cause of Reye-like syndrome is medium chain acyl-CoA dehydrogenase (MCAD) deficiency. The authors describe a gypsy boy who was repeatedly hospitalised due to symptoms of Reye-like syndrome (serious hypoglycemia, loss of consciousness, seizures, increased values of aminotransferases, decreased values of free carnitine). The diagnosis of MCAD deficiency was established by analysis of plasmatic acylcarnitines by use of tandem mass spectrometry. DNA analysis proved the most common K329E (G985) mutation in gene for MCAD deficiency in homozygous state. The authors have emphasised the advantage of tandem mass spectrometry in the diagnosis of disorders of fatty acid beta-oxidation. This highly sophisticated method can detect most of these disorders from dry blood spots disregarding the symptoms and type of mutation.

[A new approach to cholesterol]. / Nový pohlad na cholesterol.

Although much is known about hypercholesterolemia and the associated risk for the development of atherosclerosis, very little research has focused on altered cholesterol biosynthesis. Recent discovery that the biochemical basis for the human malformation syndrome, Smith-Lemli-Opitz syndrome appears to lie in altered cholesterol biosynthesis has changed this situation. Cholesterol has an extraordinary important functions in organism. Recommendations to lower serum cholesterol are widespread, yet low serum cholesterol is associated with poorly understood morbidity. Cholesterol is still an enigmatic, essential metabolite and much remains to learn about it.

[Hyperamylasemia and pancreatic diseases in children]. / Hyperamylazémia a ochorenie pankreasu u detí.

Elevated alpha-amylase activity in serum was thought for a long time to be a laboratory standard in diagnosis of acute pancreatic disease. The purpose of this study was to evaluate the clinical usefulness of routine measurement of total serum amylase (using the Boehringer Mannheim EPS method) and pancreatic isoamylase (using Boehringer Mannheim EPS method) and lipase (Kodak Eastman) in children. Authors examined the group of 93 children with abdominal pain whose age ranged from 5 to 17 years. In previous laboratory measurements using Spofa test (Slovakofarma) they were found to have elevated alpha-amylase in serum, thus the pancreatic disorder was put in question. A pancreatic disorder was proven in 9 children (9.7%) from this group. The authors consider the measurements given above to be the markers significantly improving the specificity of routine biochemistry in children with pancreatic diseases.

[Electrophoresis of alkaline phosphatase isoenzymes--the key to rapid diagnosis in transient hyperphosphatemia]. / Elektroforéza izoenzýmov alkalickej fosfatázy--kl'úc k rýchlej diagnostike tranzitórnej hyperfosfatazémie.

Using the method of electrophoretic separation of isoenzymes of serum alkaline phosphatase the authors confirmed the diagnosis of transient hyperphosphatasaemia in nine children examined in the out-patient department or hospitalized with various diagnoses in the Childrens Hospital. The typical isoenzyme picture was formed by an atypical anodal fraction and the probable bone isoenzyme corresponding to the cathodal fraction. The examination method used made it possible to differentiate rapidly and relatively simply transient hyperphosphatasaemia from other diseases associated with a high serum alkaline phosphatase activity.

[Transitory hyperphosphatasemia in childhood]. / Tranzitórna hyperfosfatazémia detského veku.

Transient hyperphosphatasaemia was detected in 11 children hospitalized at the First and Second Paediatric Clinic of the Paediatric Faculty Hospital in Bratislava in 1985-1990. The authors analyzed retrospectively 6 children from this group where it was possible to evaluate accurately the trend of serum alkaline phosphatase. In all children the high alkaline phosphatase activity was detected incidentally during the initial examination. The reason for hospitalization were in four instances respiratory infections, in one instance coeliac disease and in one instance infectious mononucleosis with infection of the urinary pathways. The maximum increase of serum alkaline phosphatase was 5-15 fold higher than the upper borderline of the reference range for the given age group. The activity declined to normal spontaneously independently on the course of the basic disease and treatment, always in the course of 3-12 weeks. The isoenzyme pattern of alkaline phosphatase with a high ratio of the thermolabile isoenzyme was typical. Finally the authors emphasize that recognition of this obscure condition which does not endanger life can spare the children many unnecessary and expensive examinations.

[Increased acid phosphatase in isolated transitory hyperphosphatasemia]. / Zvýsenie kyslej fosfatázy pri izolovanej tranzitórnej hyperfosfatazémii.

In a 13-month-old girl with typical signs of isolated transient hyperphosphatasaemia the authors found repeatedly elevated acid phosphatase values. This finding supports the hypothesis of a temporary increase of bone remodelling in this condition.