Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive ultrarare lysosomal storage disease caused by pathogenic/likely pathogenic variants in the LIPA gene. The age of onset and progression rate can significantly vary, possibly due to the nature of the underlying variants. The disorder is often misdiagnosed or undiagnosed in the Gulf Cooperation Council (GCC) countries owing to its nonspecific clinical presentation; this necessitates establishing campaigns to increase awareness among healthcare professionals and strategies for identifying and screening high-risk populations. This narrative review is based on an analysis of the available literature, complemented by key discussions among a group of recognized healthcare professionals from the GCC region with expertise in clinical genetics, hepatology, gastroenterology, and lipidology. The outcome of their discussions is a set of practical recommendations and insights aimed at assisting physicians across multiple specialties in the identification and management of individuals affected by this ultrarare genetic disorder.

Patient registries are valuable tools for epidemiological research, especially for rare diseases, and a high level of data quality is essential but not always demonstrated. Although crucial, the quality management process in patient registries rarely includes data validation. The European Cystic Fibrosis Society Patient Registry (ECFSPR) collects clinical data about people with cystic fibrosis (pwCF) in Europe (as defined by the World Health Organisation (WHO) European region). This on-site data validation project was conducted by the ECFSPR to assess feasibility of the project, data accuracy and identify areas for improvement.

The diagnosis of hereditary angioedema with a normal C1Inh was genetic. The two most frequent pathogenic variants are found in the FXII and PLG genes. Their management is similar to that of HAE patients with C1Inh deficiency but without evidence-based medicine.

To report aortic events in a large family carrying a variant in the TGFBR2 gene.

Rare diseases affect a small percentage of the population, leading to challenges such as delayed diagnoses and limited treatment options. Mobile health technologies offer solutions to improve patient outcomes, yet their application in rare diseases remains underexplored. The German citizen science project SelEe created a customizable app for the self-management of rare diseases through a co-creation process that involved patients with such conditions.

We evaluated breathing (i.e.: thoracic contribution to tidal volume in the supine position) and sleep (i.e.: apnea-hypopnea index (AHI)) before and after a 6-month of restricted Mediterranean Diet on 22 volunteers with a confirmed diagnosis of Osteogenesis Imperfecta (median age: 37.8 years; 17 women; 13 type III). At the end of the 6 months, 8 individuals (median age: 38.1 years, 5 females, 3 type III) did not spontaneously follow the diet therefore serving as the control group (CtrOI) for the 14 (median age: 34.7 years, 10 females, 9 type III) who completed the program (DietOI). AHI tended to decrease in DietOI, while it even tended to increase in CtrOI. The thoracic contribution to tidal volume in the supine position of DietOI passed from almost no expansion before diet to a significant expansion after diet; while it was negative in CtrOI indicating systematic paradoxical breathing in the supine position. This pilot study show that the main beneficial effect of diet was a to significantly expand the thorax in supine position with a tendency to reduce the AHI index.

Tuberous sclerosis complex (TSC) is a rare genetic disorder resulting in hamartomas in multiple organs, causing varied manifestations with a substantial burden of illness (BOI) for patients and caregivers. A significant component of the BOI is the high prevalence of TSC-associated epilepsy. The objective of this systematic literature review is to provide an overview of the BOI in TSC-associated epilepsy, a focus not reported in the recent review by Zöllner et al. (2020).

Lysosomal storage disorders (LSDs) are a group of rare metabolic conditions caused by enzyme deficiencies, leading to the accumulation of macromolecules within lysosomes. These disorders significantly impact patients' quality of life (QoL) and impose substantial financial burdens on families and healthcare systems. This study aimed to evaluate the daily life impact and economic burden of LSDs on patients, caregivers, the Spanish Health System (SHS), and society.

Apparent mineralocorticoid excess (AME) is a rare autosomal recessive disorder caused by biallelic inactivating variants in the HSD11B2 gene resulting in hypertension and electrolyte abnormalities due to cortisol-mediated activation of mineralocorticoid receptors. We aimed to utilize data from a large genomic database to estimate the prevalence and carrier frequency of AME, with stratification by ethnic ancestry to identify potential disparities.

Cystic fibrosis (CF) is a multi-system disease caused by CFTR dysfunction. Genetic defects in the CFTR protein cause impaired chloride and bicarbonate secretion on the apical surface of epithelial cells throughout the body. Classically, the diagnosis of CF is established based on a clinical presentation suggestive of CF along with two elevated sweat chloride test results (≥ 60 mmol/L) or the presence of two pathogenic disease-causing CFTR variants. This study aimed to characterize and compare a subset of patients who present with a CF-like phenotype and elevated sweat chlorides with ('CF control') vs. without ('cases') disease-causing CFTR variants.

Inherited epidermolysis bullosa (EB) is a rare, incurable genodermatosis characterised with recurrent skin blistering and mucosal fragility. Wound care and nursing are critical to everyday lives of children living with EB, while the profound effect of caring for a child with a painful genetic condition leaves a significant effect on quality of life of parents and the family. This study aimed to better understand the lived experiences and supportive care needs of parents of children with EB in Australia.

Cockayne Syndrome (CS) is a rare autosomal recessive genetic disease, mainly caused by ERCC8 and ERCC6 gene defect. However, many of its molecular characteristics remain unclear. In this study, molecular genetic analysis was performed on a patient to clarify her genetic etiology.

Late-onset Pompe's disease (LOPD) is a progressive treatable metabolic myopathy due to partial acid α-glucosidase (GAA) deficiency, with potential onset during the pediatric age. To date, Pompe's disease is not widely included in newborn screening panels, so that clinical suspect remains essential for timely diagnosis and management. Clinical identification of LOPD was shown to be challenging in adult patients, whereas data in children and adolescents are scanty. We conducted an Italian nationwide multicentric survey in order to delineate the characteristics of LOPD in the pediatric population. This prompted us to propose a diagnostic algorithm to facilitate the identification of LOPD in pediatrics.

Carnitine uptake deficiency (CUD) is an inherited disorder caused by SLC22A5 gene variants resulting in low plasma and intracellular carnitine concentrations. Although newborn screening (NBS) enables timely diagnosis of CUD, its efficiency is being debated. The aim of this work was to assess the benefits and limitations of NBS for CUD. A retrospective, observational single-center study was conducted on newborns born between 2017 and 2020 recalled for low free carnitine (C0) values. Biochemical, molecular, dietary and perinatal data were collected. Maternal acylcarnitine profiles and SLC22A5 genotype were also recorded, if available.

The global incidence of Hyperphenylalaninemia (HPA) demonstrates significant geographical variations, exhibiting distinct regional and ethnic characteristics in both phenotypic manifestations and genotypic profiles. To date, there remains a paucity of data regarding the genotype-phenotype correlation in pediatric patients with phenylalanine hydroxylase deficiency (PAHD) from Southwest China. This study aims to conduct a retrospective analysis of neonatal HPA prevalence and characterize PAH gene mutations in Yunnan Province in Southwest China. These findings are expected to establish an evidence base for optimizing clinical follow-up protocols, facilitating genetic counseling, and enabling prenatal molecular diagnosis for affected children.

Fabry disease (FD; OMIM # 301500) is a rare, X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A (GLA) gene. Deficiency or absence of alpha-galactosidase A (α-Gal A) enzyme activity leads to the accumulation of glycosphingolipids, specifically globotriaosylceramide (GL-3), in lysosomes leading to various symptoms and signs such as neuropathic pain, gastrointestinal manifestations, renal failure, hypertrophic cardiomyopathy and fibrosis, cardiac rhythm disturbances, heart failure, and stroke. This observational study aimed to describe the journey of patients to FD diagnosis (symptoms, comorbidities, related diagnoses, tests, procedures, and healthcare resource utilization) by assessing data from two US claims databases (Optum Clinformatics Data Mart [Optum CDM] database and Komodo Research Dataset [Komodo RD]).

Non-transfusion-dependent beta-thalassemia (β-NTDT) is characterized by ineffective erythropoiesis, increased intestinal iron absorption, and iron overload. The ferroportin inhibitor, vamifeport, has been shown to improve erythropoiesis via decreases in serum iron and transferrin saturation levels in preclinical models and healthy volunteer studies.