Diagnosis, management and treatment of the Alport syndrome - 2024 guideline on behalf of ERKNet, ERA and ESPN.

Glomerular nephropathy resulting from the genetic defects in COL4A3/4/5 genes including the classical Alport syndrome (AS) is the second commonest hereditary kidney disease characterized by persistent haematuria progressing to the need of kidney replacement therapy, frequently associated with sensorineural deafness, and occasionally with ocular anomalies. Diagnosis and management of COL4A3/4/5 glomerulopathy is a great challenge due to its phenotypic heterogeneity, multiple modes of inheritance, variable expressivity, and disease penetrance of individual variants as well as imperfect prognostic and progression factors and scarce and limited clinical trials, especially in children. As a joint initiative of the European Rare Kidney disease reference Network (ERKNet), European Renal Association (ERA Genes&Kidney) and European Society for Paediatric Nephrology (ESPN) Working Group Hereditary Kidney Disorders, a team of experts including adult and paediatric nephrologists, kidney geneticists, audiologists, ophthalmologists and a kidney pathologist were selected to perform a systematic literature review on 21 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions.

Consensus document on diagnosis and management of familial hypercholesterolemia from the Italian Society for the Study of Atherosclerosis (SISA).

Aims: Familial Hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism that causes an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Although early diagnosis and treatment of FH can significantly improve the cardiovascular prognosis, this disorder is underdiagnosed and undertreated. For these reasons the Italian Society for the Study of Atherosclerosis (SISA) assembled a Consensus Panel with the task to provide guidelines for FH diagnosis and treatment.

Role of triglyceride-glucose index in metabolic assessment of sarcoidosis patients.

Sarcoidosis is a rare granulomatous disease that can affect any organ. It leads to an increased risk of metabolic syndrome and insulin resistance, due to biochemical pathways involved in low-grade inflammation in both diseases. The aim of our retrospective case-control study was to evaluate the utility of triglyceride-glucose (TyG) index, a surrogate of insulin resistance, for metabolic assessment of sarcoidosis patients.

Gastroschisis prevalence patterns in 27 surveillance programs from 24 countries, International Clearinghouse for Birth Defects Surveillance and Research, 1980-2017.

Background: Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population.

Methods: We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe , Latin America, North America).

Validation of a Brief Form of the Self-Administered Multidimensional Prognostic Index: The SELFY-BRIEF-MPI Project.

In clinical practice, self-administered and brief tools to promptly identify older people at risk of frailty are required. The Multidimensional Prognostic Index (MPI), derived from the Comprehensive Geriatric Assessment (CGA) seems reliable enough to serve this purpose, but despite the several versions developed over the past 15 years, it lacks a self-administered and brief version. In this study, we aimed to evaluate the agreement between an abbreviated form of the SELFY-MPI (i.

Clinical Approach in the Management of Paediatric Patients with Familial Hypercholesterolemia: A National Survey Conducted by the LIPIGEN Paediatric Group.

Detection and treatment of patients with familial hypercholesterolemia (FH) starting from childhood is fundamental to reduce morbidity and mortality. The activity of National realities such as the LIPIGEN (LIpid transPort disorders Italian GEnetic Network) Paediatric Group, founded in 2018, is a milestone in this context. The aim of this exploratory survey, conducted in October 2021 among Italian lipid clinics included in the LIPIGEN Paediatric Group, was to investigate the current clinical approach in the management and treatment of paediatric patients with suspected FH.

Cardiovascular risk in rare diseases: a prognostic stratification model in a cohort of sarcoidosis patients.

Sarcoidosis is a rare granulomatous disease that can affect any organ; as other chronic diseases, it leads to increased risk of atherosclerosis and cardiovascular (CV) disease. The aim of our observational study was to define a prognostic stratification model of sarcoidosis patients based on the evaluation of CV risk through common carotid Doppler ultrasound and cardiovascular risk scores assessment; for this reason, a clinical phenotyping of sarcoidosis patients in four subgroups was done, based on the different organ involvement. A cohort of 53 sarcoidosis patients and a cohort of 48 healthy volunteers were enrolled.

Consensus guidelines for diagnosis and management of anemia in epidermolysis bullosa.

Background: Anemia is a common complication of severe forms of epidermolysis bullosa (EB). To date, there are no guidelines outlining best clinical practices to manage anemia in the EB population. The objective of this manuscript is to present the first consensus guidelines for the diagnosis and management of anemia in EB.

The Spectrum of MORC2-Related Disorders: A Potential Link to Cockayne Syndrome.

Background: Cockayne syndrome (CS) is a DNA repair disorder primarily associated with pathogenic variants in ERCC6 and ERCC8. As in other Mendelian disorders, there are a number of genetically unsolved CS cases.

Methods: We ascertained five individuals with monoallelic pathogenic variants in MORC2, previously associated with three dominantly inherited phenotypes: an axonal form of Charcot-Marie-Tooth disease type 2Z; a syndrome of developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy; and a rare form of spinal muscular atrophy.

Case report: associated cortical malformations: Case report of a novel stop-gain variant and literature review.

Malformations of cortical development (MCDs) can lead to peculiar neuroradiological patterns and clinical presentations (i.e., seizures, cerebral palsy, and intellectual disability) according to the specific genetic pathway of the brain development involved; and yet a certain degree of phenotypic heterogeneity exists even when the same gene is affected.

CARPEDIEM® for continuous kidney replacement therapy in neonates and small infants: a French multicenter retrospective study.

Background: The Cardio-Renal Pediatric Dialysis Emergency Machine (CA.R.P.

Personalized health risk assessment based on single-cell RNA sequencing analysis of a male with 45, X/48, XYYY karyotype.

Numeric sex chromosome abnormalities are commonly associated with an increased cancer risk. Here, we report a 14-year-old boy with a rare mosaic 45, X/48, XYYY karyotype presenting with subtle dysmorphic features and relative height deficiency, requiring growth hormone therapy. As only 12 postnatal cases have been described so far with very limited follow-up data, to assess the proband's long-term prognosis, including cancer risk, we performed high-throughput single-cell RNA sequencing (scRNA-seq) analysis.

Outcomes of steroid-resistant nephrotic syndrome in children not treated with intensified immunosuppression.

Background: The aim of the current PodoNet registry analysis was to evaluate the outcome of steroid-resistant nephrotic syndrome (SRNS) in children who were not treated with intensified immunosuppression (IIS), focusing on the potential for spontaneous remission and the role of angiotensin blockade on proteinuria reduction.

Methods: Ninety-five pediatric patients who did not receive any IIS were identified in the PodoNet Registry. Competing risk analyses were performed on 67 patients with nephrotic-range proteinuria at disease onset to explore the cumulative rates of complete or partial remission or progression to kidney failure, stratified by underlying etiology (genetic vs.

Sarcoidosis and autoimmunity: In the depth of a complex relationship.

Sarcoidosis is a chronic granulomatous disease that can virtually affect any organ. Its etiology is unknown, although it has been proposed that environmental or biological agents can act as triggers, ultimately leading to chronic inflammation in genetically predisposed individuals. The main component of sarcoid inflammation is represented by an exaggerated T- lymphocytic cellular response to a putative antigen that could not be efficiently cleared in the patient.

Efficacy of Long-Term Treatment of Autosomal Recessive Hypercholesterolemia With Lomitapide: A Subanalysis of the Pan-European Lomitapide Study.

Autosomal recessive hypercholesterolemia (ARH) is a rare autosomal recessive disorder of low-density lipoprotein (LDL) metabolism caused by pathogenic variants in the gene. Like homozygous familial hypercholesterolemia, ARH is resistant to conventional LDL-lowering medications and causes a high risk of atherosclerotic cardiovascular diseases (ASCVDs) and aortic valve stenosis. Lomitapide is emerging as an efficacious therapy in classical HoFH, but few data are available for ARH.

Multicentric Carpotarsal Osteolysis Syndrome Associated Nephropathy: Novel Variants of Gene and Literature Review.

Multicentric carpo-tarsal osteolysis (MCTO) is a rare osteolysis syndrome mainly involving carpal and tarsal bones usually presenting in early childhood. MCTO has autosomal dominant inheritance with heterozygous mutation in the gene. The skeletal disorder is often associated with chronic kidney disease.

Variation of the clinical spectrum and genotype-phenotype associations in Coenzyme Q10 deficiency associated glomerulopathy.

Primary Coenzyme Q10 deficiency is a rare mitochondriopathy with a wide spectrum of organ involvement, including steroid-resistant nephrotic syndrome mainly associated with disease-causing variants in the genes COQ2, COQ6 or COQ8B. We performed a systematic literature review, PodoNet, mitoNET, and CCGKDD registries queries and an online survey, collecting comprehensive clinical and genetic data of 251 patients spanning 173 published (47 updated) and 78 new cases. Kidney disease was first diagnosed at median age 1.