Long-term efficacy of migalastat in females with Fabry disease.

Background: Fabry disease is a progressive, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to variants. Females with Fabry disease often experience diagnostic delays and an underappreciated disease burden owing to their variable disease presentation and progression.

Methods: We conducted a analysis of all females from the clinical studies FACETS (NCT00925301) and ATTRACT (NCT01218659) and their open-label extensions, assessing baseline characteristics and long-term efficacy of migalastat regarding cardiac and renal function and Fabry-associated clinical events (FACEs).

Emerging role of complement system in the induction of neuroinflammation in adenylosuccinate lyase deficiency disorder.

Adenylosuccinate lyase deficiency disorder (ADSLDD) is an ultra-rare autosomal recessive metabolic condition that leads to severe neurological impairment, with an estimated global prevalence of approximately 0.00125 cases per 100,000 individuals. Clinically, ADSLDD presents in three distinct phenotypes: the fatal neonatal form, the childhood form, and the more slowly progressive form, each characterized by varying degrees of developmental and neurological dysfunction.

Fabry disease in females: organ involvement and clinical outcomes compared with the general population (103/150 characters).

Fabry disease (FD) is a rare, X-linked, progressive multi-system disorder of glycosphingolipid metabolism that causes cellular and organ damage in multiple body systems. FD has not been studied as extensively in females as in males due to greater heterogeneity of presentation and variability of disease course in females. Furthermore, despite published evidence to the contrary, females are still often referred to as carriers of FD and their symptoms assumed to be mild.

A new multisystem ERCC1-hepatorenal syndrome: insights from a clinical cohort, molecular pathogenesis, and management guidelines.

DNA repair disorders are a group of conditions characterized by progressive, multisystem phenotypes. Defining new clinical presentations of these disorders is essential for optimizing patient care. ERCC1-XPF is a multifunctional endonuclease involved in nucleotide excision repair (NER) and interstrand crosslink (ICL) repair.

Research Review of Myhre Syndrome.

This research review of Myhre syndrome is a summary of published articles which provide a valuable resource for readers, researchers, and future authors. It traces the evolution of the Laryngotracheal-Arthropathy-Prognathism-Short Stature (LAPS) syndrome to the current eponym of Myhre syndrome. These allelic disorders are caused by pathogenic variants in SMAD4.

The phenotypic spectrum of the Cornelia de Lange-like "Alazami-Yuan syndrome": A case report of the 7th diagnosed individual and review of the literature.

We present a 17-year-old female with a childhood clinical diagnosis of Cornelia de Lange Syndrome (CdLS), however later genetic testing identified compound heterozygous variants in , consistent with AYS. This case report adds to the phenotypic spectrum observed in AYS, and draws connections to transcriptional pathways between CdLS and AYS.

Safety and efficacy of migalastat in adolescent patients with Fabry disease: Results from ASPIRE, a phase 3b, open-label, single-arm, 12-month clinical trial, and its open-label extension.

Fabry disease (FD) is a progressive, multisystemic, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to galactosidase alpha (GLA) gene variants. Although clinical manifestations of FD often appear in childhood, approved treatments for the management of FD in children and adolescents are limited. ASPIRE (NCT03500094) was a phase 3b, two-stage, open-label, multicenter study evaluating the safety, pharmacokinetics, and efficacy of migalastat in adolescents 12 to <18 years, ≥ 45 kg with FD and amenable GLA variants.

Dual Diagnosis of Fragile X Syndrome and DEPDC5-Related Disorder Emphasizes DEPDC5's Role Beyond Familial Epilepsy: A Case Report and Literature Review.

Dep domain-containing Protein 5 (DEPDC5), encoded by the gene DEPDC5, regulates the cell cycle by inhibiting the mTORC1 pathway in response to amino acid deficiency. Loss of function DEPDC5 variants are recognized to present as focal familial epilepsy; however, associations with comorbid brain malformations and neurodevelopmental disorders have also been reported. mTOR inhibitors were found to benefit DEPDC5-knockout mice.

Guidance for shared decision-making regarding orchiectomy in individuals with differences of sex development due to 17-β-hydroxysteroid dehydrogenase type 3 deficiency.

17β-hydroxysteroid dehydrogenase type 3 deficiency is a 46,XY difference of sex development (DSD) that may present in childhood with inguinal testes or at puberty following virilization. We present four individuals, assigned female at birth, to highlight complexities and considerations surrounding orchiectomy. We reviewed the literature and created a "FACT sheet" to guide shared decision-making for patients, parents, and providers.

A Dual Diagnosis of Okur-Chung Neurodevelopmental Syndrome and Becker Muscular Dystrophy: Inquiry Into the Lower Limits of Neurodevelopmental Functioning Attributable to Muscular Dystrophy.

Purpose: This case discusses the limits of neurodevelopmental functioning attributable to Duchenne's Muscular Dystrophy (DMD) dysfunction.

Method: A 3-year-old male presented with global developmental delay, growth failure, and dysmorphic facial features. An SNP microarray revealed an interstitial duplication in exon 55 of DMD suggestive of Becker Muscular Dystrophy (BMD), but his degree of delays led to follow-up exome sequencing revealing a pathogenic CSNK2A1 variant diagnostic for Okur-Chung Neurodevelopmental Syndrome.

A Case Study of a Female Infant With Primary Hypertrophic Osteoarthropathy Demonstrates That Early Initiation of Celecoxib Slows but Does Not Prevent Symptom Progression.

Primary Hypertrophic Osteoarthropathy (PHOAR1) is characterized by autosomal recessive loss of function variants in 15-hydroxyprostaglandin dehydrogenase (HPGD) leading to digital clubbing, periostosis, pachydermia, and severe hyperhidrosis. HPGD catalyzes the first step of prostaglandin E2 (PGE2) degradation. Selective COX-2 inhibitors have proved beneficial in adults, though it is unknown if early initiation of COX-2 inhibitors can alter the natural history of PHOAR1.

and variants are the underlying cause of Perrault-like syndrome and cardiac anomalies in a patient.

Recent studies have established an association between variants and Perrault syndrome. In this case report, we present a female patient with Perrault syndrome and cardiomyopathy, resulting from variants in and , respectively.

Complex genomic rearrangements of the Y chromosome in a premature infant.

Background: Chromoanagenesis is an umbrella term used to describe catastrophic "all at once" cellular events leading to the chaotic reconstruction of chromosomes. It is characterized by numerous rearrangements involving a small number of chromosomes/loci, copy number gains in combination with deletions, reconstruction of chromosomal fragments with improper order/orientation, and preserved heterozygosity in copy number neutral regions. Chromoanagesis is frequently described in association with cancer; however, it has also been described in the germline.

Expanding the phenotype of neurofibromatosis type 1 microdeletion syndrome.

Neurofibromatosis type 1 (NF-1) microdeletion syndrome accounts for 5 to 11% of individuals with NF-1. The aim of our study was to characterize a large cohort of individuals with NF-1 microdeletion syndrome and expand its natural history. We conducted a retrospective chart review from 1994 to 2024 of individuals with NF-1 microdeletion syndrome followed at two large Neurofibromatosis Clinics.

Phenotypic variability in Joubert syndrome is partially explained by ciliary pathophysiology.

Introduction: Joubert syndrome (JS) arises from defects of primary cilia resulting in potential malformations of the brain, kidneys, eyes, liver, and limbs. Several of the 35+ genes associated with JS have recognized genotype/phenotype correlations, but most genes have not had enough reported individuals to draw meaningful conclusions.

Methods: A PubMed literature review identified 688 individuals with JS across 32 genes and 112 publications to bolster known genotype/phenotype relationships and identify new correlations.

Prenatal and infantile diagnosis of craniosynostosis in individuals with RASopathies.

Fetuses with RASopathies can have a wide variety of anomalies including increased nuchal translucency, hydrops fetalis, and structural anomalies (typically cardiac and renal). There are few reports that describe prenatal-onset craniosynostosis in association with a RASopathy diagnosis. We present clinical and molecular characteristics of five individuals with RASopathy and craniosynostosis.

Consensus recommendations for the treatment and management of patients with Fabry disease on migalastat: a modified Delphi study.

Objective: Fabry disease is a progressive disorder caused by deficiency of the α-galactosidase A enzyme (α-Gal A), leading to multisystemic organ damage with heterogenous clinical presentation. The addition of the oral chaperone therapy migalastat to the available treatment options for Fabry disease is not yet universally reflected in all treatment guidelines. These consensus recommendations are intended to provide guidance for the treatment and monitoring of patients with Fabry disease receiving migalastat.

RNA sequencing reveals a complete picture of a homozygous missense variant in a patient with VPS13D movement disorder: a case report and review of the literature.

RNA sequencing (RNA-seq) is a complementary diagnostic tool to exome sequencing (ES), only recently clinically available to undiagnosed patients post-ES, that provides functional information on variants of unknown significance (VUS) by evaluating its effect on RNA transcription. ES became clinically available in the early 2010s and promised an agnostic platform for patients with a neurological disease, especially for those who believed to have a genetic etiology. However, the massive data generated by ES pose challenges in variant interpretation, especially for rare missense, synonymous, and deep intronic variants that may have a splicing effect.

Global reach of over 20 years of experience in the patient-centered Fabry Registry: Advancement of Fabry disease expertise and dissemination of real-world evidence to the Fabry community.

Fabry disease (FD, α-galactosidase A deficiency) is a rare, progressive, complex lysosomal storage disorder affecting multiple organ systems with a diverse spectrum of clinical phenotypes, particularly among female patients. Knowledge of its clinical course was still limited in 2001 when FD-specific therapies first became available and the Fabry Registry (NCT00196742; sponsor: Sanofi) was initiated as a global observational study. The Fabry Registry has now been operational for over 20 years, overseen by expert Boards of Advisors, and has collected real-world demographic and longitudinal clinical data from more than 8000 individuals with FD.

Congenital Hypothyroidism: Screening and Management.

Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Newborn screening (NBS) for CH should be performed in all infants. Prompt diagnosis by NBS leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood.

Congenital Hypothyroidism: Screening and Management.

Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Prompt diagnosis by newborn screening (NBS) leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet established in all countries globally.

Prevalence of lymphedema among Anderson-Fabry disease patients: A report from the Fabry registry.

Background: Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease due to a genetic variation in the α-galactosidase A (GLA) gene. As a result, the activity of the α-galactosidase A (AGAL-A) enzyme is reduced or absent, which causes sphingolipid deposition within different body parts. AFD typically manifests with cardiovascular, renal, cerebrovascular, and dermatologic involvement.