Training and temporally validating an NTCP model of acute toxicity after whole breast radiotherapy, including the impact of advanced delivery techniques.

Purpose: The aim is to train and validate a multivariable Normal Tissue Complication Probability (NTCP) model predicting acute skin reactions in patients with breast cancer receiving adjuvant Radiotherapy (RT).

Methods And Materials: We retrospectively reviewed 1570 single-institute patients with breast cancer treated with whole breast irradiation (40 Gy/15fr). The patients were divided into training (n = 878, treated with 3d-CRT, from 2009 to 2017) and validation cohorts (n = 692, treated from 2017 to 2021, including advanced RT techniques).

Biochemical Pattern of Methylmalonyl-CoA Epimerase Deficiency Identified in Newborn Screening: A Case Report.

Methylmalonyl-CoA epimerase enzyme (MCEE) is responsible for catalyzing the isomeric conversion between D- and L-methylmalonyl-CoA, an intermediate along the conversion of propionyl-CoA to succinyl-CoA. A dedicated test for MCEE deficiency is not included in the newborn screening (NBS) panels but it can be incidentally identified when investigating methylmalonic acidemia and propionic acidemia. Here, we report for the first time the biochemical description of a case detected by NBS.

A young boy with ventricular arrhythmias and thyroid dysgenesis: two genes are not enough?

Congenital hypothyroidism (CH) may be caused by biallelic variants in the TSHR gene. CH due to thyroid dysgenesis has also been linked to pathogenic variants of the nucleotide kinase 2, homeobox 5 (NKX2-5) gene, which can also cause sudden cardiac death from ventricular arrhythmia. In particular, the NKX2-5 p.

Expanded Newborn Screening in Italy Using Tandem Mass Spectrometry: Two Years of National Experience.

Newborn screening (NBS) for inborn errors of metabolism is one of the most advanced tools for secondary prevention in medicine, as it allows early diagnosis and prompt treatment initiation. The expanded newborn screening was introduced in Italy between 2016 and 2017 (Law 167/2016; DM 13 October 2016; DPCM 12-1-2017). A total of 1,586,578 infants born in Italy were screened between January 2017 and December 2020.

Benefits of rescreening newborns of mothers affected by autoimmune hypothyroidism.

Introduction: Infants of mothers with autoimmune hypothyroidism (AH) are at risk of developing late-onset hypothyroidism, often escaping at newborn screening. This condition might be caused both by the action of maternal antibodies and/or by maternal treatment.

Objectives: The aim of this study is to evaluate the prevalence of AH in the mothers of children born in Veneto region, Italy, and to define what is the most appropriate management for these newborns.

Twenty Years of Neonatal Screening for Congenital Adrenal Hyperplasia in North-Eastern Italy: Role of Liquid Chromatography-Tandem Mass Spectrometry as a Second-Tier Test.

Background: Newborn screening for congenital adrenal hyperplasia (CAH) based on 17-hydroxyprogesterone (17-OHP) concentration in dried blood spots has been taking place in North-Eastern Italy since 2001. Since 2017, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been introduced, for the first time in Italy, as a second-tier test.

Aims: Our study aims to evaluate, on the one hand, the effectiveness of the newborn screening for CAH after 20 years of testing and, on the other, the impact that the introduction of the second-tier test had on the diagnostic accuracy of the screening program.

A Gain-of-Function Mutation on Gene and Its Possible Pathogenic Role in Branched-Chain Amino Acid Metabolism.

BCKDK is an important key regulator of branched-chain ketoacid dehydrogenase complex activity by phosphorylating and so inactivating branched-chain ketoacid dehydrogenases, the rate-limiting enzyme of the branched-chain amino acid metabolism. We identified, by whole exome-sequencing analysis, the p.His162Gln variant of the gene in a neonate, picked up by newborn screening, with a biochemical phenotype of a mild form of maple syrup urine disease (MSUD).

Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy.

Biotinidase deficiency (BD) is an autosomal recessive disease causing a defect in the biotin-releasing enzyme. Newborn screening (NBS) allows early diagnosis and treatment, ensuring excellent prognosis. The aim of this study was to describe our experience in the diagnosis, treatment, and follow-up showing key strategies and unsolved questions of the management of BD patients.

Children with premature pubarche: is an alterated neonatal 17-Ohp screening test a predictive factor?

Background: Neonatal screening for 21 hydroxylase deficiency is designed to detect classical form of congenital adrenal hyperplasia (CAH). It is still unclear whether newborns who result false positives at neonatal screening might later develop signs of androgen excess. The aim of this study is to verify whether a slightly elevated 17-OHP at newborn screening is a predictive factor for premature pubarche.

High-protein goat's milk diet identified through newborn screening: clinical warning of a potentially dangerous dietetic practice.

Objective: Breast-feeding is an unequalled way of providing optimal food for infants' healthy growth and development and the WHO recommends that infants should be exclusively breast-fed for the first 6 months of life. For mothers who are unable to breast-feed or who decide not to, infant formulas are the safest alternative. Despite recommendations, it is possible that parents make potentially harmful nutritional choices for their children because of cultural beliefs or misinformation on infant nutrition.

Congenital hypothyroidism with delayed TSH elevation in low-birth-weight infants: incidence, diagnosis and management.

Objective: To evaluate the incidence of congenital hypothyroidism (CH) with delayed TSH elevation among low-birth-weight (LBW) newborns in North-Eastern Italy and to verify if they need a second or third screening.

Design: Analysis of clinical and biochemical data of newborns affected by CH with delayed TSH elevation identified by neonatal screening.

Methods: Data of all newborns with birth weight (BW) <2500 g and evidence of delayed TSH elevation at newborn screening were collected between 2011 and 2014.

Idiopathic Juvenile Osteoporosis: Clinical Experience from a Single Centre and Screening of LRP5 and LRP6 Genes.

We report clinical findings, bone mineral density (BMD) and bone biopsy data in ten children with features of classic idiopathic juvenile osteoporosis (IJO). We also screened the patients for mutations in LRP5 and LRP6. We found low BMD in the lumbar spine, the hip and distal radius.

Analysis of the d3-growth hormone receptor polymorphism in large cohorts of small, appropriate and large for gestational age newborns.

Background: Several studies evidenced a possible role of the d3-Growth Hormone Receptor (GHR) polymorphism in fetal growth. The GHR genotype distribution was studied in small (SGA) and appropriate (AGA) for gestational age newborns but never in the large (LGA) for gestational age babies. The aim of this study was to evaluate the frequencies of this polymorphism in a large cohort of SGA, AGA and LGA newborns.

Identification of a novel pax8 gene sequence variant in four members of the same family: from congenital hypothyroidism with thyroid hypoplasia to mild subclinical hypothyroidism.

Background: Congenital hypothyroidism is often secondary to thyroid dysgenesis, including thyroid agenesis, hypoplasia, ectopic thyroid tissue or cysts. Loss of function mutations in TSHR, PAX8, NKX2.1, NKX2.

3-hydroxyacyl-coenzyme a dehydrogenase deficiency: identification of a new mutation causing hyperinsulinemic hypoketotic hypoglycemia, altered organic acids and acylcarnitines concentrations.

The human HADH gene encodes the short-chain-L-3-hydroxyacyl-CoA dehydrogenase, the enzyme which catalyzes the third step of the β-oxidation of the fatty acids in the mitochondrial matrix. Loss-of-function mutations in the HADH gene lead to short-chain-L-3-hydroxyacyl-CoA dehydrogenase deficiency, an autosomal recessive genetic defect of unknown prevalence with a wide spectrum of phenotypic variability. As in other metabolic diseases, the diagnostic relevance of the biochemical evaluations, plasma acylcarnitines, and urinary organic acids, are crucially dependent on the clinical conditions of the patient during specimen collection.

Lack of expression of SERPINF1, the gene coding for pigment epithelium-derived factor, causes progressively deforming osteogenesis imperfecta with normal type I collagen.

Osteogenesis imperfecta (OI) is a clinically heterogeneous heritable connective tissue disorder, characterized by low bone mass and reduced strength, which result in susceptibility to fracture and bone deformities. In most cases it is caused by dominant mutations in type I collagen genes, COL1A1 and COL1A2. Recessive forms, which collectively account for approximately 5% of cases of osteogenesis imperfecta detected in North America and Europe, are caused instead by mutations in various genes coding for proteins involved in collagen posttranslational modifications, folding, and secretion.

Possible andrologic markers in elevated neonatal 17-hydroxyprogesterone.

In this prospective study, we analyzed 30 male infants with increased neonatal 17-hydroxyprogesterone (17OH-P) (patients) and for comparison 52 age-matched healthy babies (control subjects) with the aim of investigating the hypothalamic-pituitary-testis axis in the first 6 months of life. Although T, FSH, and LH levels were not significantly different in patients and control subjects, inhibin B was higher in patients than in control subjects. Therefore we suggest a clinical follow-up of these babies during childhood and puberty to verify the evolution of their condition.

Implementation of a congenital hypothyroidism newborn screening procedure with mutation detection on genomic DNA extracted from blood spots: the experience of the Italian northeastern reference center.

After a couple of decades from the institution of nationwide congenital hypothyroidism (CH) newborn screening program, the first generation properly treated is now displaying normal reproductive rate and the causative molecular defects are spreading from one generation to the next. In the present study we propose a method of detection of mutations in the thyrotropin receptor (TSHR) and in the paired box 8 (PAX8) genes that have been proved to be responsible for some forms of CH. The method, carried out by means of denaturing high-performance liquid chromatography (DHPLC) followed by direct sequencing, takes advantage of the CH newborn screening procedure, because genomic DNA for the analysis is extracted from the same blood spot collected for recall confirmation.