Digital microfluidic platform for dried blood spot newborn screening of lysosomal storage diseases in Campania region (Italy): Findings from the first year pilot project.

Background: Newborn screening (NBS) is a simple, non-invasive test that allows for the early identification of genetic diseases within the first days of a newborn's life. The aim of NBS is to detect potentially fatal or disabling conditions in newborns as early as possible, before the onset of disease symptoms. Early diagnosis enables timely treatments and improves the quality of life for affected patients.

A specific serum lipid signature characterizes patients with glycogen storage disease type Ia.

Glycogen storage disease type Ia (GSDIa) is a rare, inherited glucose-6-phosphatase-α (G6Pase-α) deficiency-induced carbohydrate metabolism disorder. Although hyperlipidemia is a hallmark of GSDI, the extent of lipid metabolism disruption remains incompletely understood. Lipidomic analysis was performed to characterize the serum lipidome in patients with GSDIa, by including age- and sex-matched healthy controls and age-matched hypercholesterolemic controls.

Endocrine involvement in hepatic glycogen storage diseases: pathophysiology and implications for care.

Hepatic glycogen storage diseases constitute a group of disorders due to defects in the enzymes and transporters involved in glycogen breakdown and synthesis in the liver. Although hypoglycemia and hepatomegaly are the primary manifestations of (most of) hepatic GSDs, involvement of the endocrine system has been reported at multiple levels in individuals with hepatic GSDs. While some endocrine abnormalities (e.

Mitochondrial reprogramming in peripheral blood mononuclear cells of patients with glycogen storage disease type Ia.

Background: Glycogen storage disease type Ia (GSDIa) is an inborn metabolic disorder caused by the deficiency of glucose-6-phospatase-α (G6Pase-α) leading to mitochondrial dysfunction. It remains unclear whether mitochondrial dysfunction is present in patients' peripheral blood mononuclear cells (PBMC) and whether dietary treatment can play a role. The aim of this study was to investigate mitochondrial function in PBMC of GSDIa patients.

Recurrent, founder and hypomorphic variants contribute to the genetic landscape of Joubert syndrome.

Background: Joubert syndrome (JS) is a neurodevelopmental ciliopathy characterised by a distinctive mid-hindbrain malformation, the 'molar tooth sign'. Over 40 JS-associated genes are known, accounting for two-thirds of cases.

Methods: While most variants are novel or extremely rare, we report on 11 recurring variants in seven genes, including three known 'founder variants' in the Ashkenazi Jewish, Hutterite and Finnish populations.

Obstructive Sleep Apnoea in Children with Down Syndrome: A Multidisciplinary Approach.

A comprehensive evaluation of obstructive sleep apnoea (OSA) may allow for the development of more efficient management of Down syndrome (DS). We aimed to evaluate the effect of a multidisciplinary approach to DS with OSA. A total of 48 DS children aged 4−12 years were prospectively investigated with nasal endoscopy, orthodontic examination, and overnight polygraphy (PG); the Italian Child Sleep Habits Questionnaire (CSHQ-IT) was filled out by the mothers.

Endocrine system involvement in patients with RASopathies: A case series.

Background And Objectives: Endocrine complications have been described in patients affected by RASopathies but no systematic assessment has been reported. In this study, we investigate the prevalence of endocrine disorders in a consecutive unselected cohort of patients with RASopathies.

Study Design: 72 patients with a genetically confirmed RASopathy (Noonan syndrome [NS], N=53; 29 LEOPARD syndrome [LS], N=2; cardiofaciocutaneous syndrome [CFCS], N=14; subjects showing co-occurring pathogenic variants in and , N=3) and an age- and sex-matched healthy controls were included in the study.

Long-term monitoring for short/branched-chain acyl-CoA dehydrogenase deficiency: A single-center 4-year experience and open issues.

Introduction: Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) is an inherited disorder of L-isoleucine metabolism due to mutations in the gene. The role of current diagnostic biomarkers [i.e.

Bone metabolism in patients with type 1 neurofibromatosis: key role of sun exposure and physical activity.

Bone metabolism has been rarely investigated in children affected by Neurofibromatosis type 1 (NF1). Aim of the present study was to assess bone mineral metabolism in children and adults NF1 patients, to determine the relevant factors potentially involved in the development of reduced bone mineral density (BMD), and provide possible therapeutic intervention in NF1 patients. 114 NF1 patients and sex and age matched controls were enrolled into the study.

Immune responses to alglucosidase in infantile Pompe disease: recommendations from an Italian pediatric expert panel.

Background: Classic infantile onset of Pompe disease (c-IOPD) leads to hypotonia and hypertrophic cardiomyopathy within the first days to weeks of life and, without treatment, patients die of cardiorespiratory failure in their first 1-2 years of life. Enzymatic replacement therapy (ERT) with alglucosidase alfa is the only available treatment, but adverse immune reactions can reduce ERT's effectiveness and safety. It is therefore very important to identify strategies to prevent and manage these complications.

RASopathies and hemostatic abnormalities: key role of platelet dysfunction.

Background: Bleeding anomalies have been reported in patients affected by Noonan syndrome. No study has been performed in patients with molecularly confirmed RASopathy. We aimed to characterize the frequency and types of bleeding disorders in patients with RASopathies and evaluate any significant association with laboratory findings.

Beneficial Effects of Slow-Release Large Neutral Amino Acids after a Phenylalanine Oral Load in Patients with Phenylketonuria.

The mainstay of phenylketonuria treatment is a low protein diet, supplemented with phenylalanine (Phe)-free protein substitutes and micronutrients. Adhering to this diet is challenging, and even patients with good metabolic control who follow the dietary prescriptions in everyday life ignore the recommendations occasionally. The present study explores the ability of slow-release large neutral amino acids (srLNAAs) to prevent Phe increase following a Phe dietary load.

Risk of autoimmune diseases in patients with RASopathies: systematic study of humoral and cellular immunity.

Background: Abnormalities of the immune system are rarely reported in patients affected by RASopathies. Aim of the current study was to investigate the prevalence of immune system dysfunction in a cohort of patients affected by RASopathies.

Study Design: A group of 69 patients was enrolled: 60 at the Federico II University, Naples, 7 at University Magna Graecia of Catanzaro, 2 at "Scuola Medica Salernitana", Salerno.

Clinical variability of neurofibromatosis 1: A modifying role of cooccurring PTPN11 variants and atypical brain MRI findings.

Neurofibromatosis 1 (NF1) is a disorder characterized by variable expressivity caused by loss-of-function variants in NF1, encoding neurofibromin, a protein negatively controlling RAS signaling. We evaluated whether concurrent variation in proteins functionally linked to neurofibromin contribute to the variable expressivity of NF1. Parallel sequencing of a RASopathy gene panel in 138 individuals with molecularly confirmed clinical diagnosis of NF1 identified missense variants in PTPN11, encoding SHP2, a positive regulator of RAS signaling, in four subjects from three unrelated families.

Clinical heterogeneity of Kabuki syndrome in a cohort of Italian patients and review of the literature.

Kabuki syndrome (KS) is a well-recognized disorder characterized by postnatal growth deficiency, dysmorphic facial features, skeletal anomalies, and intellectual disability. The syndrome is caused by KMT2D gene mutations or less frequently KDM6A gene mutations or deletions. We report a systematic evaluation of KS patients from Campania region of Italy; data were also compared with literature ones.

Crohn disease-like enterocolitis remission after empagliflozin treatment in a child with glycogen storage disease type Ib: a case report.

Background: Besides major clinical/biochemical features, neutropenia and inflammatory bowel disease (IBD) constitute common complications of Glycogen storage disease type Ib (GSD Ib). However, their management is still challenging. Although previous reports have shown benefit of empagliflozin administration on neutropenia, no follow-up data on bowel (macro/microscopic) morphology are available.

Expanding the neurological and behavioral phenotype of White-Sutton syndrome: a case report.

Background: White-Sutton (WHSUS) is a recently recognized syndrome caused by mutations of the POGZ gene. Approximately 70 patients have been reported to date. Intellectual disability, hypotonia, behavioral abnormalities, autism, and typical facial dysmorphisms are recognized as WHSUS features; however, still few patients receive a comprehensive psychometric, behavioral and neurological examination.

Epigallocatechin-3-Gallate Plus Omega-3 Restores the Mitochondrial Complex I and FF-ATP Synthase Activities in PBMCs of Young Children with Down Syndrome: A Pilot Study of Safety and Efficacy.

Down syndrome (DS) is a major genetic cause of intellectual disability. DS pathogenesis has not been fully elucidated, and no specific pharmacological therapy is available. DYRK1A overexpression, oxidative stress and mitochondrial dysfunction were described in trisomy 21.

Parkinson's disease in Gaucher disease patients: what's changing in the counseling and management of patients and their relatives?

Background: How to address the counseling of lifetime risk of developing Parkinson's disease in patients with Gaucher disease and their family members carrying a single variant of the GBA1 gene is not yet clearly defined. In addition, there is no set way of managing Gaucher disease patients, taking into account the possibility that they may show features of Parkinson's disease.

Methods: Starting from an overview on what has recently changed in our knowledge on this issue and grouping the experiences of healthcare providers of Gaucher disease patients, we outline a path of counseling and management of Parkinson's disease risk in Gaucher disease patients and their relatives.

Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience.

Background: In GM1 gangliosidosis the lack of function of β-galactosidase results in an accumulation of GM1 ganglioside and related glycoconjugates in visceral organs, and particularly in the central nervous system, leading to severe disability and premature death. In the type 2 form of the disease, early intervention would be important to avoid precocious complications. To date, there are no effective therapeutic options in preventing progressive neurological deterioration.

Large Neutral Amino Acids (LNAAs) Supplementation Improves Neuropsychological Performances in Adult Patients with Phenylketonuria.

Phenylketonuria is an inborn error of phenylalanine (Phe) metabolism diagnosed by newborn screening and treated early with diet. Although diet prevents intellectual disability, patients often show impairment of executive functions, working memory, sustained attention, and cognitive flexibility. Large neutral amino acids (LNAAs) have been proposed as a dietary supplement for PKU adults.

Imbalanced cortisol concentrations in glycogen storage disease type I: evidence for a possible link between endocrine regulation and metabolic derangement.

Background: Glycogen storage disease type I (GSDI) is an inborn error of carbohydrate metabolism caused by mutations of either the G6PC gene (GSDIa) or the SLC37A4 gene (GSDIb). Glucose 6-phosphate (G6P) availability has been shown to modulate 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), an ER-bound enzyme catalyzing the local conversion of inactive cortisone into active cortisol. Adrenal cortex assessment has never been performed in GSDI.

Clinical significance of family history and bicuspid aortic valve in children and young adult patients with Marfan syndrome.

Background: Marfan syndrome is an autosomal dominant disorder of the connective tissue, whose cardinal features affect eyes, musculoskeletal, and cardiovascular system. Despite prevalence and natural history of cardiovascular manifestation are well known in adults, little is known about children and young adult patients. The aim of this study was to describe a well-characterised cohort of consecutive children and young patients with marfan syndrome, looking at the impact of family history and presence of bicuspid aortic valve on disease severity.