Molecular and Cytogenetic Analysis of Romanian Patients with Differences in Sex Development.

Unlabelled: Differences in sex development (DSD) are often correlated with a genetic etiology. This study aimed to assess the etiology of DSD patients following a protocol of genetic testing.

Materials And Methods: This study prospectively investigated a total of 267 patients with DSD who presented to Clinical Emergency Hospital for Children Cluj-Napoca between January 2012 and December 2019.

Early clinical signs in lysosomal diseases.

Background And Aim: The lysosomal storage diseases are a group of monogenic diseases with multisystemic impairment and chronic progression induced by the deficiency of lysosomal acid hydrolases involved in the breakdown of various macromolecules. The accumulation occurs in the macrophages of the reticule-endothelial system and causes enlargement and functional impairment. The mainly involved organs are the brain, liver, spleen, bones, joints, airways, lungs, and heart.

Cardiovascular manifestations in Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant inherited disease of the connective tissue with multiorgan involvement (skeleton, cardiovascular, eyes, skin, lungs). Cardiovascular involvement is variable and represents the major cause of morbidity and mortality in Marfan syndrome. We provide a comprehensive description of cardiovascular manifestations in Marfan syndrome, genotype-phenotype correlations and assessment of cardiovascular abnormalities and complications.

Diagnostic, treatment and outcome possibilities in achondroplasia.

Introduction: Achondroplasia is a common form of chondrodysplasia. It is transmitted by autosomal dominant trait. The disease is determined by mutations in receptor-3 gene of the fibroblast growth factor.

Cardiac Manifestations in a Group of Romanian Patients with Gaucher Disease Type 1 (a Monocentric Study).

Gaucher disease (GD), one of the most common lysosomal disorders, is characterised by clinical heterogeneity. Cardiac involvement is rare and refers to pulmonary hypertension (PH), valvular abnormalities and myocardial infiltrative damage. The aim of this study was to evaluate cardiac involvement in a group of Romanian GD patients.

16q24.3 Microduplication in a Patient With Developmental Delay, Intellectual Disability, Short Stature, and Nonspecific Dysmorphic Features: Case Report and Review of the Literature.

We describe the case of a seven-year-old female patient who presented in our service with severe developmental delay, intellectual disability, facial dysmorphism, and femur fracture, observed in the context of very low bone mineral density. Array-based single nucleotide polymorphism (SNP array) analysis identified a 113 kb duplication involving the morbid OMIM genes: (exon1), , and genes. ANKRD11 deletions are frequently described in association with KBG syndrome, the duplications being less frequent (one case described before).

Gene variants of osteoprotegerin, estrogen-, calcitonin- and vitamin D-receptor genes and serum markers of bone metabolism in patients with Gaucher disease type 1.

Purpose: Osteopathy/osteoporosis in Gaucher disease type 1 (GD1) shows variable responses to enzyme replacement therapy (ERT); the pathogenesis is incompletely understood. We aimed to investigate the effects of several gene variants on bone mineral density (BMD) and serum markers of bone metabolism in GD1.

Patients And Methods: Fifty adult Caucasian patients with GD1/117 controls were genotyped for gene variants in the osteoprotegerin (TNFRSF11B; OPG), estrogen receptor alpha, calcitonin receptor (CALCR), and vitamin D receptor (VDR) genes.

Clinical and genetic characteristics in a group of 45 patients with Turner syndrome (monocentric study).

Introduction: Recent years have seen a shift in perspective on Turner syndrome, as it is no longer considered a significant disability due to therapeutic advances. The delay of diagnosis and the underdiagnosis are common in Turner syndrome, especially because of the great phenotypic variability and lack of firm diagnostic criteria.

Aim: Our first aim was to assess the clinical and the cytogenetic characteristics and growth rate in growth hormone (GH)-treated patients as compared to those with spontaneous growth.

Problems in the Diagnosis of Cyclic Vomiting Syndrome in Children.

The cyclic vomiting syndrome (CVS) is an infrequent condition in pediatric practice, in which recurrent vomiting episodes are followed by asymptomatic periods. The authors report the case of an 8-year and 2-month old child who had been hospitalized on several occasions for persistent vomiting accompanied by nausea, and periumbilical and epigastric abdominal pain. The child's anamnesis and clinical examination determined the doctors to suspect aCVS, which was later confirmed due toruling out all of the differential diagnoses: infectious, drug-related or surgical causes.

Modelling long-term evolution of chitotriosidase in non-neuronopathic Gaucher disease.

Chitotriosidase, an enzyme secreted by activated macrophages, is widely used as a biomarker for therapeutic monitoring and patient follow-up in Gaucher disease (GD), a lysosomal disorder caused by an inherited deficiency of glucocerebrosidase. We analyzed the long-term evolution of chitotriosidase aiming to establish an accurate model that describes the influence of enzyme replacement therapy (ERT) and the impact of several covariates. A total of 55 patients with non-neuronopathic (type 1) GD were followed for almost 17 years (during a maximum of 7.

Cholelithiasis in Patients with Gaucher Disease type 1: Risk Factors and the Role of ABCG5/ABCG8 Gene Variants.

Background And Aim: Patients with Gaucher disease type 1 (GD1) show an altered lipid profile and a certain degree of insulin resistance, which might contribute to cholelithiasis (CL) and could possibly be associated with ABCG5/ABCG8 gene variants. We aimed to investigate the prevalence of CL in Caucasian adult patients with GD1 and the possible risk factors, including gene variants of the ABCG5/ABCG8 genes.

Methods: 61 Caucasian patients with GD1 (38 female/23male), aged 18-62 years and 61 healthy subjects matched for age, gender and BMI, without CL, for comparison of lipid profiles.

Clinical and Genetic Characteristics of Romanian Patients with Mucopolysaccharidosis Type II.

Background: Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare X-linked disorder caused by deficiency of iduronate-2-sulfatase (I2S) enzyme, which leads to the accumulation of partially digested glycosaminoglycans (GAGs) in the lysosomes and induces multisystemic alteration (coarse facial features; skeletal dysplasia; hepatosplenomegaly; joint stiffness and contractures; heart, lung, vision, and hearing disability; profound neurological decline).The purpose of this study is to present the clinical and genetic characteristics of Romanian patients with Hunter syndrome and the genotype-phenotype correlation.

Material And Methods: 15 unrelated patients, with MPS II ranging from mild (4 subjects) to severe phenotype (11 subjects) aged 2 to 20 years, were evaluated clinically, cognitive development, enzyme assay and molecular analysis.

Evaluation of neopterin as a biomarker for the monitoring of Gaucher disease patients.

Objectives: Biomarker research is an important area of investigation in Gaucher disease, caused by an inherited deficiency of a lysosomal enzyme, glucocerebrosidase. We evaluated the usefulness of neopterin, as a novel biomarker reflecting chronic inflammation and immune system activation in Gaucher disease and analysed its evolution in response to enzyme replacement therapy (ERT).

Methods: Circulating plasma neopterin levels in 31 patients with non-neuronopathic Gaucher disease were measured before and after the onset of ERT and were compared with those of 18 healthy controls.

A Novel Nonsense Mutation of the AGL Gene in a Romanian Patient with Glycogen Storage Disease Type IIIa.

Background. Glycogen storage disease type III (GSDIII) is a rare metabolic disorder with autosomal recessive inheritance, caused by deficiency of the glycogen debranching enzyme. There is a high phenotypic variability due to different mutations in the AGL gene.

The c.301_302delAG PROP1 gene mutation in Romanian patients with multiple pituitary hormone deficiency.

Objective: To establish the frequency of the c.301_302 delAG mutation of the PROP1 gene in Romanian patients with multiple pituitary hormone deficiency (MPHD).

Subjects And Methods: Somatic assessment, hormonal test, bone age, magnetic resonance imaging of the pituitary gland, and molecular diagnosis were performed in 26 patients with MPHD (7 patients with familial form of MPHD and 19 patients with sporadic form of MPHD).

Osteoarthropathy in mucopolysaccharidosis type II.

Introduction: Mucopolysaccharidosis type II (MPS type II, Hunter syndrome) is a rare (~ 1/1500.000), X-linked inherited disorder (affects boys) due to deficiency of the lysosomal enzyme iduronate sulfatase (Xq.28).

Dynamic changes of lipid profile in Romanian patients with Gaucher disease type 1 under enzyme replacement therapy: a prospective study.

Background: Dyslipidemia in Gaucher disease includes reduced total, low-density lipoprotein (LDL)-, and high-density lipoprotein (HDL)-cholesterol (C). No prospective analysis of lipid profile changes in treatment-naïve patients under enzyme replacement therapy (ERT) is available.

Methods: We analyzed lipid profile changes during ERT in a prospective controlled manner.

Alterations in lipid and carbohydrate metabolism in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Background: Classic 21-hydroxylase deficiency (21HD) presents some traits of the metabolic syndrome.

Aim: To characterize discrete alterations of lipid and carbohydrate metabolism in children and young adults with classic 21HD, which could predict early atherogenesis.

Patients And Methods: Twenty-seven Caucasian patients with classic 21HD (4-31 years); 27 sex-, age- and BMI-matched controls.

Baseline characteristics and outcome in Romanian patients with Gaucher disease type 1.

Background/aim: To present clinical and genetic characteristics of all Romanian patients with Gaucher disease type 1, in whom specific diagnosis has been confirmed by enzymatic and molecular methods and to analyze their outcome with and without enzymatic replacement therapy (ERT).

Patients, Methods: There are fifty patients (F/M - 1.63/1) with Gaucher disease type 1.

Bone mineral density and bone turnover in Romanian children and young adults with classical 21-hydroxylase deficiency are influenced by glucocorticoid replacement therapy.

Objective: It remains controversial if glucocorticoid replacement therapy impairs bone mineral density (BMD) in young patients with 21-hydroxylase deficiency. We aimed to analyze the impact of treatment variables, phenotype and genotype on BMD and bone metabolism in these patients.

Design: Cross-sectional study.

MRI findings and genotype analysis in patients with childhood onset growth hormone deficiency--correlation with severity of hypopituitarism.

Aim: To evaluate the relationship between pituitary size, PIT1 and PROP1 genotype, and the severity of childhood onset growth hormone deficiency (coGHD).

Patients: Forty-four patients with coGHD (34 M; 9.7 +/- 4.

Evaluation of viral replication in children with chronic hepatitis B with and without interferon treatment.

Background: In chronic infection with hepatitis virus B the fact that HBeAg becomes negative does not always mean suppression of viral replication.

Method: HBV replication was assessed in 74 patients with chronic hepatitis or viral B cirrhosis, in whom diagnosis was made according to clinical, biological, and histological criteria. The patients were divided into two groups: group I (36 patients with interferon- therapy, 3 million U/m 2/ dose, 3 doses/week over a period of 4-6 months) and group II (control group of 38 patients who did not undergo interferon therapy).

21-Hydroxylase and 11beta-hydroxylase mutations in Romanian patients with classic congenital adrenal hyperplasia.

Context: Congenital adrenal hyperplasia (CAH) comprises autosomal recessive disorders mainly due to defects in the 21-hydroxylase (CYP21) gene.

Objective: The study aimed to perform molecular characterization in 43 Romanian patients with classical CAH forms diagnosed at the Center for Genetic Diseases of the Pediatric Clinic/University Cluj (38 with 21-hydroxylase deficiency, five with 11beta-hydroxylase deficiency), to determine the frequency of mutations in the CYP21A2 gene and attempt a genotype-phenotype correlation in patients with 21-hydroxylase deficiency.

Design: Molecular analysis was performed by direct sequencing of PCR amplified products of the CYP21A2 and CYP11B1 genes.

Three new 46,XX male patients: a clinical, cytogenetic and molecular analysis.

Background: XX males range phenotypically from completely masculinised individuals to true hermaphrodites and include a subset of SRY negative patients. The correlation between genotype (SRY+/-) and phenotype is still unclear.

Aim: To report three new patients with this rare condition, one of whom was diagnosed prenatally and another was SRY negative, and to verify in our patients whether the presence of SRY results in a more masculinised phenotype.