Genetic Contributions to the Development of Complications in Preterm Newborns.

Aim: We aimed to identify specific polymorphisms of genes encoding for vascular endothelial growth factor A (VEGFA), endothelial nitric oxide synthase (eNOS), renin-angiotensin system (angiotensinogen gene [AGT], angiotensinogen type 1 receptor [AGTR1], angiotensin-converting enzyme [ACE]), and heme oxygenase-1 (HMOX-1) in a cohort of preterm infants and correlate their presence with the development of respiratory distress syndrome (RDS) requiring mechanical ventilation (MV), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP).

Study Design: We carried out a retrospective study to evaluate the allele frequency and genotype distribution of polymorphisms of VEGFA, eNOS, AGT, AGTR1, ACE, and HMOX-1 in a population of preterm neonates (n=342) with a gestational age ≤28 weeks according to the presence or absence of RDS requiring MV, BPD, IVH, or ROP. Moreover, we evaluated through the haplotype reconstruction analysis whether combinations of the selected polymorphisms are related to the occurrence of RDS, BPD, IVH and ROP.

A case of acute post-streptococcal glomerulonephritis that developed posterior reversible encephalopathy syndrome.

A 10-year male patient presented with swelling in the face, legs and scrotal area which developed 8 days after tonsillitis treatment. Acute post-sterotococcal glomerulonephritis (APSGN) was considered in the patient whose urinalysis revealed hematuria and proteinuria at nephrotic level, whose urea, creatinine, lipid profile and anti-streptolysine O antibody levels were increased, albumin and C3 value were decreased and whose 24-hour urine test revealed proteinuria. Renal biopsy was found to be compatible with APSGN.

Intellectual disability and epilepsy in down syndrome.

Unlabelled: Down Syndrome (DS) is the most common genetic cause of mental retardation, with a reported frequency of epilepsy between 1.4-17% (1). There is a paucity of data in the literature regarding epilepsy in Down syndrome and its relation to intellectual disability.

Role of optic microscopy for early diagnosis of Menkes disease.

We report the case of a male patient with a normal development in the first three months of life, presenting for global regression, central axial hypotonic syndrome, pyramidal syndrome, focal epileptic seizures, and a particular aspect of the hair - almost absent, short, sparse, lightly colored, at age of five months, becoming coarse, twisted (kinky hair) by the age of 21 months. Different diseases associate similar neurological and macroscopic aspect of the hair (biotinidase deficiency, argininosuccinic aciduria, aminoaciduria, giant axonal neuropathy, trichothiodistrophy and Menkes syndrome). The microscopic aspect of the patient's hair showing normal hair, silver colored hair, hair shafts twisting 1800, trichoclasis, and trichoptilosis, was highly characteristic for Menkes disease.

Influence of urbanization level and Gross Domestic Product on the prevalence of adolescent obesity in Poland.

Introduction: Obesity is considered as a major disease of twenty-first century civilization. Its occurrence in Poland and worldwide has been increasing steadily for many years. Several factors play an important role in the development of overweight and obesity.

Screening of lysosomal storage disorders: application of the online trapping-and-cleanup liquid chromatography/mass spectrometry method for mucopolysaccharidosis I.

In recent years, new treatments have become available to treat some lysosomal storage disorders (LSDs) and many studies suggest that there is a benefit with starting therapy early. Newborn screening should detect diseases early enough for prompt treatment. Some countries include additional conditions, such as some LSDs, into their newborn screening panels.

Measurement of succinyl-carnitine and methylmalonyl-carnitine on dried blood spot by liquid chromatography-tandem mass spectrometry.

Methylmalonic aciduria (MMA) is one of the most frequent organic acidurias, a class of diseases caused by enzymatic defects mainly involved in the catabolism of branched-chain amino acids. Recently, mild MMA and C4-dicarboxylyl-carnitine (C4DC-C) accumulation have been reported in patients carrying mutation in genes encoding the α-subunit (SUCLG1) and the β-subunit (SUCLA2) of the ADP-forming succinyl-CoA synthetase (SCS). We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify in dried blood spot the two isobaric compounds of C4DC-C, succinyl-carnitine and methylmalonyl-carnitine, to allow the differential diagnosis between classical MMA and SCS-related defects.

Children who develop type 1 diabetes early in life show low levels of carnitine and amino acids at birth: does this finding shed light on the etiopathogenesis of the disease?

Background: Children and adolescents with overt type 1 diabetes (T1D) have been found to show an altered carnitine profile. This pattern has not previously been analyzed in neonates before onset of the disease.

Materials And Methods: Fifty children who developed T1D during the first 6 years of life, born and living in the Tuscany and Umbria Regions of Italy, were identified and 200 controls were recruited into the study.

The efficacy of cognitive training programs in children and adolescents: a meta-analysis.

Background: Cognitive therapies are intended to improve basic cognitive functions, whatever the cause of the deficiency may be. Children and adolescents with various cognitive deficits are treated with behavioral therapeutic and computer-supported training programs. We here report the first meta-analysis of the efficacy of such programs.

The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry.

Severe combined immunodeficiency due to adenosine-deaminase defect (ADA-SCID) is usually deadly in childhood because of severe recurrent infections. When clinical diagnosis is done, permanent damages due to infections or metabolite accumulation are often present. Gene therapy, bone marrow transplantation or enzyme replacement therapy may be effective if started early.

A rapid liquid chromatography tandem mass spectrometry-based method for measuring propranolol on dried blood spots.

Propranolol, a non-selective beta blocker drug, is used in young infants and newborns for treating several heart diseases; its pharmacokinetics has been extensively evaluated in adult patients using extrapolation to treat pediatric population. The purpose of the present study was to develop and validate a method to measure propranolol levels in dried blood spots. The analysis was performed by using liquid chromatography/tandem mass spectrometry operating in multiple reaction monitoring mode.

Rapid and sensitive LC-MS/MS method for the analysis of antibiotic linezolid on dried blood spot.

Linezolid is a new drug from the oxazolidinone class of antibiotics used against mycobacteria and multi-drug resistant (MDR) Gram-positive bacterial infections, which may are also glycopeptide-resistant. The drug usage in pediatric age needs an accurate drug monitoring for effective patient management. The aim of this study was to evaluate the use of dried blood spot (DBS) specimens to determinate linezolid levels during treatment.

LC-MS/MS method for simultaneous determination on a dried blood spot of multiple analytes relevant for treatment monitoring in patients with tyrosinemia type I.

Tyrosinemia type 1 is caused by deficiency of fumarylacetoacetate hydrolase. The enzymatic defect impairs the conversion of fumarylacetoacetate to fumarate, causing accumulation of succinylacetone which induces severe liver and kidney dysfunction along with mutagenic changes and hepatocellular carcinoma. Treatment is based on nitisinone (NTBC), an enzymatic inhibitor which suppresses succinylacetone production.

GM1 gangliosidosis and Morquio B disease: an update on genetic alterations and clinical findings.

GM1 gangliosidosis and Morquio B syndrome, both arising from beta-galactosidase (GLB1) deficiency, are very rare lysosomal storage diseases with an incidence of about 1:100,000-1:200,000 live births worldwide. Here we report the beta-galactosidase gene (GLB1) mutation analysis of 21 unrelated GM1 gangliosidosis patients, and of 4 Morquio B patients, of whom two are brothers. Clinical features of the patients were collected and compared with those in literature.

Newborn Screening for Tyrosinemia Type I: Further Evidence that Succinylacetone Determination on Blood Spot Is Essential.

Tyrosinemia type I is a genetic disorder characterized by accumulation in the blood and urine of the toxic metabolite succinylacetone (SUAC), not detectable in healthy samples. In many countries, newborns are screened for tyrosinemia type I using tyrosine as a primary marker. Unfortunately, tyrosine accumulation may take longer to occur and it may be not obvious when specimens are collected, in the first few days of life, as for newborn screening.

Rapid assay of rufinamide in dried blood spots by a new liquid chromatography-tandem mass spectrometric method.

Rufinamide (RUF) is a new antiepileptic drug with efficacy in several types of seizures. The aim of this study was to evaluate the use of dried blood spot (DBS) specimens to determinate RUF levels during treatment. Therapeutic drug monitoring of RUF could be useful in routine clinical practice.

Functional studies of new GLA gene mutations leading to conformational Fabry disease.

Fabry Disease (FD) is an X-linked multisystemic lysosomal disorder caused by mutations of alpha-galactosidase (GLA) gene. Only a few of the 450 genetic lesions identified so far have been characterised by in vitro expression studies. Thus the significance of newly identified GLA nucleotide variants in FD patients which lead to alpha-galactosidase (GAL-A) amino acid substitutions or intronic changes can be uncertain.

Hypocitrullinemia in expanded newborn screening by LC-MS/MS is not a reliable marker for ornithine transcarbamylase deficiency.

In an expanded newborn screening program for inborn errors of metabolism by LC-MS/MS in Tuscany, six newborns out of 169,000 showed decreased blood citrulline levels. In one of them, molecular analysis of the OTC gene identified the known p.Trp265Leu mutation, which is correlated with late-onset ornithine transcarbamylase deficiency (OTCD).

Rapid assay of topiramate in dried blood spots by a new liquid chromatography-tandem mass spectrometric method.

Topiramate (TPM) is a new antiepiletic drug with efficacy in several types of seizures. Therapeutic drug monitoring of TPM is essential for effective patient management. The aim of this study was to evaluate the use of dried blood spot (DBS) specimens to determinate the TPM levels during the treatment.

GALNS gene expression profiling in Morquio A patients' fibroblasts.

Background: Quantification studies of mutated mRNAs have not been carried out on Morquio A patients. Such studies are very important for the determination of stability of premature termination codons (PTC) bearing transcripts in order to assess the appropriateness of introducing the newly developed therapeutic strategies such as "stop codon read-through therapy".

Methods: This paper focuses on the study of the GALNS gene and mRNAs in two severe forms of Morquio A patients' fibroblasts with development of a new and rapid real-time RT-PCR for detection and quantification of absolute mRNA copy number.

The potential action of galactose as a "chemical chaperone": increase of beta galactosidase activity in fibroblasts from an adult GM1-gangliosidosis patient.

Background: The glycosphingolipid storage disorder GM1-gangliosidosis is a severe neurodegenerative condition for which no therapy is currently available. Protein misfolding in lysosomal defects may have the potential to be corrected by chemical chaperones: in vitro and clinical approaches are being investigated.

Aims: We investigated the in vitro effect of galactose on some lysosomal hydrolases, and its in vitro efficacy as a chemical chaperone in GM1-gangliosidosis.

Unbalanced GLA mRNAs ratio quantified by real-time PCR in Fabry patients' fibroblasts results in Fabry disease.

Total or partial deficiency of the human lysosomal hydrolase alpha-galactosidase A is responsible for Fabry disease, the X-linked inborn error of glycosphingolipid metabolism. Together with the predominant alpha-galactosidase A gene mRNA product encoding the lysosomal enzyme, a weakly regulated alternatively spliced alpha-galactosidase A transcript is expressed in normal tissues, but its overexpression, due to the intronic g.9331G>A mutation, leads to the cardiac variant.

Different genotypes in a large Italian family with recurrent hereditary fructose intolerance.

Objectives: Hereditary fructose intolerance is caused by a deficiency of the aldolase B enzyme, which is expressed in the liver, small intestine and kidneys. Patients usually show a marked aversion to fruits and sweets; if, however, it is not diagnosed, persistent or incidental ingestion of fructose might be lethal. Our paper aims at improving the clinical and molecular characterizations of these patients, to avoid dangerous misdiagnoses.

'Fou rire prodromique' as the heralding symptom of lenticular infarction, caused by dissection of the internal carotid artery in a 12-year-old boy.

A 12-year-old, right-handed boy experienced a pathological fit of laughter before a sudden right hemiplegia. Magnetic resonance imaging showed a left basal ganglia infarction, induced by a left internal carotid dissection. Arteriography revealed an underlying fibromuscular dysplasia.