The N221D variant in is highly prevalent in childhood obesity and can influence the metabolic profile.

Objectives: To study the prevalence and influence on metabolic profile of the prohormone-convertase-1 (PCSK1) N221D variant in childhood obesity, proven its role in the leptin-melanocortin signaling pathway as in proinsulin and other prohormone cleavage.

Methods: Transversal study of 1066 children with obesity (mean age and BMI Z-score 10.38 ± 3.

Impact of muscular symptoms and/or pain on disease characteristics, disability, and quality of life in adult patients with hypophosphatasia: A cross-sectional analysis from the Global HPP Registry.

Introduction: Hypophosphatasia (HPP) manifests in adults as fractures/pseudofractures, pain, muscle weakness, and other functional impairments. Better phenotypic disease characterization is needed to help recognize disability and treat patients with HPP.

Methods: Baseline/pretreatment demographic, clinical characteristic, and patient-reported disability/health-related quality-of-life (HRQoL) data from adults (≥18 y) in the Global HPP Registry (NCT02306720) were stratified by presence of overt skeletal manifestations (skeletal group) versus muscular/pain manifestations without skeletal manifestations (muscular/pain group) and summarized descriptively.

Carbohydrate metabolism impairment in children and adolescents with cystic fibrosis.

Introduction: Development of cystic fibrosis-related diabetes (CFRD) is associated with worsening of nutritional status and lung function, as well as increased mortality. The relevance of diagnosing the «pre-diabetic» status in these patients has not been addressed and the utility of HbA1c measurement in these patients is under discussion.

Aim: To study and characterise the different categories of carbohydrate metabolism impairment in paediatric patients with cystic fibrosis.

Clinical profiles of treated and untreated adults with hypophosphatasia in the Global HPP Registry.

Background: The clinical signs and symptoms of hypophosphatasia (HPP) can manifest during any stage of life. The age at which a patient's symptoms are reported can impact access to targeted treatment with enzyme replacement therapy (asfotase alfa), as this treatment is indicated for patients with pediatric-onset HPP in most countries. As such, many patients reported to have adult-onset HPP typically do not receive treatment.

Missplicing due to a synonymous, T96= exonic substitution in the T-box transcription factor TBX19 resulting in isolated ACTH deficiency.

Summary: Congenital isolated ACTH deficiency (IAD) is a rare condition characterised by low plasma ACTH and serum cortisol with normal production of other pituitary hormones. TBX19 (also known as TPIT) is a T-box pituitary restricted transcription factor important for POMC gene transcription and terminal differentiation of POMC-expressing cells. TBX19 gene mutations have been shown to cause neonatal-onset congenital IAD.

Adult height and long-term outcomes after rhIGF-1 therapy in two patients with PAPP-A2 deficiency.

PAPP-A2 deficiency is a novel syndrome characterized by short stature due to low IGF bioactivity, skeletal abnormalities and decreased bone mineral density (BMD). Treatment with recombinant human IGF-1 (rhIGF-1) for 1 year demonstrated to increase growth velocity and BMD, without reported adverse effects, but data regarding the long-term efficacy and safety of rhIGF-1 administration in this entity has not yet been reported. Two Spanish siblings with short stature due to a homozygous loss-of-function mutation in the PAPP-A2 gene (p.

Aldosterone deficiency with a hormone profile mimicking pseudohypoaldosteronism.

Background Aldosterone deficiency (hypoaldosteronism) or aldosterone resistance (pseudohypoaldosteronism) both result in defective aldosterone activity. Case presentation A 42-day-old man presented with failure to thrive, hyponatremia, high urine sodium output, severe hyperkalemia and high plasma renin activity and aldosterone levels. NR3C2, SCNN1A, B and G sequencing showed no variants.

Recommendations for Diagnosis and Treatment of Pseudohypoparathyroidism and Related Disorders: An Updated Practical Tool for Physicians and Patients.

Patients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky build, early-onset obesity, ectopic ossifications, and neurodevelopmental deficits, as well as hormonal resistance most prominently to parathyroid hormone (PTH). In addition to these alterations, patients may develop other hormonal resistances, leading to overt or subclinical hypothyroidism, hypogonadism and growth hormone (GH) deficiency, impaired growth without measurable evidence for hormonal abnormalities, type 2 diabetes, and skeletal issues with potentially severe limitation of mobility. PHP and related disorders are primarily clinical diagnoses.

Burden of Illness in Adults With Hypophosphatasia: Data From the Global Hypophosphatasia Patient Registry.

Hypophosphatasia (HPP) is a rare, inherited, metabolic disease caused by deficient tissue non-specific alkaline phosphatase activity. This study aims to assess patient-reported pain, disability and health-related quality of life (HRQoL) in a real-world cohort of adults with HPP who were not receiving asfotase alfa during the analysis. Adults (≥18 years old) with HPP (confirmed by ALPL gene mutation and/or low serum alkaline phosphatase activity for age/sex) were identified from the Global HPP Registry (NCT02306720).

LZTR1: Genotype Expansion in Noonan Syndrome.

Background: LZTR1 participates in RAS protein degradation, hence limiting the RAS/MAPK cascade. Pathogenic mutations in LZTR1 (MIM:600574) have been described in a few patients with Noonan syndrome (NS). Three patients with LZTR1 mutations of different genetic transmission and NS phenotype are herein characterized.

Frequency and age at occurrence of clinical manifestations of disease in patients with hypophosphatasia: a systematic literature review.

Background: Hypophosphatasia (HPP) is a rare, inherited, metabolic disease caused by tissue-nonspecific alkaline phosphatase deficiency, characterized by bone mineralization defects and systemic complications. Understanding of the clinical course and burden of HPP is limited by its rarity. This systematic literature review and synthesis of case report data aimed to determine the frequency and timing of clinical HPP manifestations and events.

[Implication in Paediatrics of the First International Consensus Statement for the Diagnosis and management of pseudohypoparathyroidism and related disorders].

Since Albright and co-workers described pseudohypoparathyroidism in 1942 as the combined presence of hypocalcaemia and hyperphosphataemia associated with the existence of tissue resistance to parathyroid hormone (PTH) action upon normal renal function, great advances have been made in the clinical and genetic profile of patients affected by this condition. Furthermore, not only have genetic bases of pseudohypoparathyroidism been unravelled, but also variants in other genes involved in the PTH/PTHrP signalling pathway through Gsα, have been identified as the cause of diseases that share clinical features with pseudohypoparathyroidism. In the paediatric setting, the first symptoms suggesting the impairment of this signalling pathway are the presence of subcutaneous ossifications, brachydactyly and/or early onset obesity, followed by the possible development of PTH resistance.

[Parental obesity is associated with the severity of childhood obesity and its comorbidities].

Introduction: The influence of parental obesity on their obese offsprings is acknowledged but insufficiently characterised.

Patients And Methods: Retrospective study of 800 obese patients (45.2% girls; age: 10.

[Influence of neonatal anthropometry on the comorbidities of the obese patient].

Introduction: Small for gestational age (SGA) newborns show an increased risk of several diseases such as short stature, childhood obesity, and metabolic comorbidities.

Patients And Methods: The study included 883 obese patients (47% females/53% males; mean age: 10.33±3.

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement.

This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features.

Clinical management of childhood hyperthyroidism with and without Down syndrome: a longitudinal study at a single center.

Background The approach to the clinical management of Graves' disease (GD) is debatable. This study aimed to identify predictors of remission in pediatric GD. Methods A longitudinal study of 36 children and adolescents with GD followed from 1997 to 2017 at a single tertiary hospital was performed.

Frequent and Rare HABP2 Variants Are Not Associated with Increased Susceptibility to Familial Nonmedullary Thyroid Carcinoma in the Spanish Population.

Background/aims: A genomic HABP2 variant was proposed to be responsible for familial nonmedullary thyroid carcinoma (FNMTC). However, its involvement has been questioned in subsequent studies. We aimed to identify genetic HABP2 mutations in a series of FNMTC patients and investigate their involvement in the disease.

Vulvar fetal rhabdomyoma mimicking 46XX sex differentiation disorder.

Rhabdomiomas are rare mesenchymal benign tumors of striated muscle origin. Setting aside the cardiac (most atrial) rhabdomiomas typically associated to neurocutaneous syndromes (tuberous sclerosis), extracardiac rhabdomyomas appear clinically as a subcutaneous nodule or as a submucosal polypoid lesion. Among them, three main histologic subtypes can be differentiated on the basis of the degree of tumor differentiation: 1) fetal rhabdomioma, usually diagnosed during childhood and almost exclusively located in the in the head and neck region with rare reports in other locations; 2) adult rhabdomioma; and 3) genital rhabdomioma, reported to occur in the lower genital tract of young and middle-aged women and, exceptionally, in children (5).