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Natural-History Mapping of Lysosomal Storage Disorders (LSDs): Gaucher Disease as a Model for Precision Care.

Natural-history datasets have become pivotal for drug development and for shaping clinical-practice guidelines in rare diseases, yet many lysosomal storage disorders would benefit from deep phenotyping and modern analytic methods. Our objective was to integrate the past decade of genomic, cellular, treatment-outcome, and regulatory advances into a practical framework for capturing and interpreting natural-history data, using Gaucher disease (GD) as a paradigm. We reviewed more than 300 peer-reviewed articles (2005-2025), FDA guidance documents, and output from large real-world registries. Part

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… Weinreb , “ Timing of Initiation of Enzyme Replacement Therapy After Diagnosis of Type 1 Gaucher Disease: Effect on Incidence of Avascular Necrosis ,” British Journal of Haematology 147 , no. 4 ( 2009 ): 561 – 570 . 19732054 10.1111/j.1365-2141.2009.07872.x PMC2774157 2 S. M. Lo , J. Liu , F. … Cole , et al., “ Dose‐Response Relationships for Enzyme Replacement Therapy With Imiglucerase/Alglucerase in Patients With Gaucher Disease Type 1 ,” Genetics in Medicine 11 , no. 2 ( 2009 ): 92 – 100 . 19265748 10.1097/GIM.0b013e31818e2c19 PMC3793250 43 D. Amato , T. Stachiw , J. T. …

Storage diseases with hypertrophic cardiomyopathy phenotype.

Never judge a book by its cover, nor assume hypertrophic cardiomyopathy (HCM) as sarcomeric, as appearances can deceive. HCM phenocopies account for a 5-10% of the cases, mainly represented by storage diseases, flagged by the increasing prevalence of senile cardiac amyloid in developing countries. Multisystemic and heterogeneous presentation of these entities is a challenge for clinicians, and time delay in diagnosis is a major concern. Promising drugs and gene-specific tailored therapies are under development, therefore, more than ever, appropriate understanding of these conditions is mandato

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… Enzyme replacement therapy (ERT) with alglucosidase alfa treatment should be started as soon as possible, as it has shown to improve cardiomyopathy, ventilation free-survival and overall survival. Without ERT, surveillance is estimated in around two years 81 . … Chen M Zhang L Quan S 2017 Enzyme replacement therapy for infantile-onset Pompe disease Cochrane Database Syst Rev 11 CD011539 29155436 10.1002/14651858.CD011539.pub2 PMC6486223 82. …

Uncommon Factors Leading to Nephrotic Syndrome.

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransfe

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… Enzyme replacement therapy, in which recombinant LCAT is administered to patients, as well as gene therapy, which aims to correct the LCAT gene mutation, are just some of the promising approaches. … Enzyme replacement therapy, where recombinant LCAT enzyme is administered to patients, holds promise but faces challenges related to enzyme delivery and stability. …

Recommendations on the follow-up of patients with Gaucher disease in Spain: Results from a Delphi survey.

Management of Gaucher disease (GD) is challenging due to its wide genotypic and phenotypic variability and changing clinical manifestations due to effective treatment. Sixteen face-to-face meetings with experts were held in order to discuss daily clinical practice and identify controversies regarding the management of GD. With this information, a questionnaire with 93 recommendations for different clinical scenarios was designed, and a Delphi survey among 86 physicians with experience in GD was conducted. Consensus was reached on 73 out of the 93 items. Recommendations on follow-up of adult an

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… TABLE 4 Follow‐up of GD during pregnancy, breastfeeding and postmenopause Abbreviations: ERT, enzyme replacement therapy; GD, Gaucher disease. a Items that underwent a second round of vote. … Individualization of long‐term enzyme replacement therapy for Gaucher disease . Genet Med . 2005 ; 7 ( 2 ): 105 ‐ 110 . doi: 10.1097/01.gim.0000153660.88672.3c 15714077 11 Weinreb NJ , Aggio MC , Andersson HC , et al. …

Heyde Syndrome Unveiled: A Case Report with Current Literature Review and Molecular Insights.

Heyde syndrome, marked by aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome, is often underreported. Shear stress from a narrowed aortic valve degrades von Willebrand factor multimers, leading to angiodysplasia formation and von Willebrand factor deficiency. This case report aims to raise clinician awareness of Heyde syndrome, its complexity, and the need for a multidisciplinary approach. We present a 75-year-old man with aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome type 2A. The patient w

Glycoprotein Non-Metastatic Protein B: An Emerging Biomarker for Lysosomal Dysfunction in Macrophages.

Several diseases are caused by inherited defects in lysosomes, the so-called lysosomal storage disorders (LSDs). In some of these LSDs, tissue macrophages transform into prominent storage cells, as is the case in Gaucher disease. Here, macrophages become the characteristic Gaucher cells filled with lysosomes laden with glucosylceramide, because of their impaired enzymatic degradation. Biomarkers of Gaucher cells were actively searched, particularly after the development of costly therapies based on enzyme supplementation and substrate reduction. Proteins selectively expressed by storage macrop

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… Enzyme replacement therapy: Conception, chaos and culmination. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 2003;358:915–919. doi: 10.1098/rstb.2003.1269. 60. Barton N.W., Furbish F.S., Murray G.J., Garfield M., Brady R.O. … Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease. Blood. 2011;118:5767–5773. doi: 10.1182/blood-2011-07-366955. 92. …

Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities.

Subcutaneous delivery of biotherapeutics has become a valuable alternative to intravenous administration across many disease areas. Although the pharmacokinetic profiles of subcutaneous and intravenous formulations differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and to result in reduced drug delivery-related healthcare costs and resource use. The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from both health-economic and scientific perspectives. The article c

Acid sphingomyelinase deficiency in France: a retrospective survival study.

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) or Niemann-Pick disease types A, A/B, and B is a progressive, life-limiting, autosomal recessive disorder caused by sphingomyelin phosphodiesterase 1 (SMPD1) gene mutations. There is a need to increase the understanding of morbidity and mortality across children to adults diagnosed with ASMD. METHODS: This observational retrospective survey analysed medical records of patients with ASMD with retrievable data from 27 hospitals in France, diagnosed/followed up between 1st January 1990 and 31st December 2020. Eligible records were abstracted to

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… Olipudase alfa is an enzyme replacement therapy approved for treating non-central nervous system manifestations of ASMD in paediatric and adult patients across >35 countries, including Japan, the European Union, and the United States [ 21 , 22 ]. … One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency. Genet Med. 2021;23:1543–50. 33875845 10.1038/s41436-021-01156-3 PMC8354848 25. …

Hypophosphatemia in cancer patients.

Dysregulation of phosphorus homeostasis resulting in hypophosphatemia is common in cancer patients and can result in serious complications and impact outcomes. Several factors, including critical illness, nutritional status, cancer type and therapy, influence the development of hypophosphatemia. Hypophosphatemia can develop as a result of phosphaturic mesenchymal tumors or as a paraneoplastic phenomenon. The clinical presentation for hypophosphatemia varies depending on the duration and severity of the hypophosphatemia and affects several organ systems. Among other serious effects, hypophospha

Advances in Peptidomimetics for Next-Generation Therapeutics: Strategies, Modifications, and Applications.

Over the past two decades, peptide drug discovery has experienced a remarkable renaissance, with organic chemistry and biotechnology emerging as pivotal tools for developing peptidomimetics that exhibit improved stability, specificity, and bioavailability compared to conventional peptides. This review systematically examines methodologies for modifying peptide backbones to achieve targeted properties, highlighting recent advances facilitated by modern biotechnological innovations for novel molecular transformations. Additionally, the review emphasizes the practical applications of peptides and

VEXAS Syndrome-Review.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined refractory adult-onset autoinflammatory syndrome caused by somatic mutations in the ubiquitin-like modifier-activating enzyme 1 (UBA1) gene in hematopoietic stem and progenitor cells, resulting in a shift in UBA1 isoform expression. Thus, patients develop a spectrum of systemic inflammatory manifestations and hematologic symptoms. To date, patients respond poorly to immune suppressive drugs, except high-dose glucocorticoids, and no treatment guidelines have been established. Given the high mortality ra

Multiple Myeloma, Hyperviscosity, Hemodialysis Filter Clogging, and Antigen Excess Artifact: A Case Report.

Kidney involvement in multiple myeloma can result in kidney failure. Unlike Waldenström macroglobulinemia, hyperviscosity syndrome is a rare occurrence in multiple myeloma. Timely detection of hyperviscosity syndrome and initiation of plasma exchange to remove paraproteins can significantly alter the clinical course and be potentially lifesaving. We report a case of hospitalized patient with kidney failure due to multiple myeloma not in remission who experienced shortened hemodialysis sessions due to early dialysis filter failure due to hyperviscosity, which was later corrected with plasmapher

Diagnosis, treatment, and follow-up of patients with hypophosphatasia.

INTRODUCTION: Hypophosphatasia is a rare inherited systemic metabolic disorder, with an estimated prevalence in the severe forms of the disease of 1/100.000-1/300.000, that affects the typical architecture of bone, leading to defective mineralization during growth and remodeling. It is characterized by loss-of-function variants in the ALPL gene, resulting in low activity of tissue-nonspecific alkaline phosphatase. In severe cases, it can be fatal. OBJECTIVE: To generate recommendations on the diagnosis, treatment, and follow-up of patients with hypophosphatasia based on available evidence. M

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… What are the goals of treat a patient with enzyme replacement therapy (ERT)? … Therapeutic scheme of enzyme replacement therapy with Asfotase alfa The recommended dose of Asfotase alfa is 6 mg/kg/week, administered according to the manufacturer's recommendations. (Strong in favor). …

Gaucher Disease Types I and III Responded Well to Substrate Reduction Therapy Using Eliglustat.

Gaucher disease (GD) causes the accumulation of glucocerebrosides in various organs, resulting in hepatosplenomegaly, anemia, decreased platelet counts, and bone disorders. Glucosylsphingosine accumulates in the brain and causes central nervous system (CNS) disorders. GD can be classified into types I (without CNS disorders), II, and III. Substrate reduction therapy (SRT) is an oral therapy that improves patients' quality of life; however, its effect on type III GD is unknown. We administered SRT to GD types I and III patients and found it effective. Malignancy is a late complication of GD, bu

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… The main treatment modalities include enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). ERT is a more common treatment than SRT; however, it requires frequent visits to the hospital for the administration of intravenous infusion every two weeks. … Eliglustat compared with imiglucerase in patients with Gaucher's disease type 1 stabilised on enzyme replacement therapy: a phase 3, randomized, open-label, non-inferiority trial. Lancet 385: 2355-2362, 2015. 5. The International Collaborative Gaucher Group. …

Genetics, cardiac phenotype and cardiovascular outcomes in Fabry disease patients in Finland.

AIMS: To investigate the genetics, cardiac phenotype and cardiovascular outcomes of Finnish Fabry patients. METHODS AND RESULTS: Among the 109 patients with Fabry disease (FD) diagnosed in Finland by 2018, 97 (89%; 32 males and 65 females, mean ages 42 and 52 years) were followed for a mean of 12 years. Data on genetics, phenotypes, cardiac imaging and cardiovascular outcomes were collected from the Fabry Registry and medical records. The 26 families with FD harboured 22 different hemi-/heterozygous GLA variants, most commonly p.R227X, p.A143T or p.P409A. The Fabry phenotype in males was clas

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… FD can be treated with specific enzyme replacement therapy (ERT), or in some cases, chaperone therapy migalastat. … replacement therapy; n , number; normal ranges: 18–39 years: >89 mL/min/1.73 m 2 ; SD, standard deviation …

Pancreatic Proteolytic Enzymes and Cancer: New Support for an Old Theory.

In 1905, the embryologist John Beard first proposed that pancreatic proteolytic enzymes had potential as a treatment for cancer. His theories were dismissed by the medical world a decade later, but various practitioners have kept the concept alive through the publication of case reports of cancer patients treated with pancreatic proteolytic enzymes. In the last 2 decades, studies of the role of proteases in physiology have made it clear that they do more than digest food. This article reviews the history of the clinical use of pancreatic proteolytic enzymes in cancer treatment, and recent rese

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboran

Clinical review: specific aspects of acute renal failure in cancer patients.

Acute renal failure (ARF) in cancer patients is a dreadful complication that causes substantial morbidity and mortality. Moreover, ARF may preclude optimal cancer treatment by requiring a decrease in chemotherapy dosage or by contraindicating potentially curative treatment. The pathways leading to ARF in cancer patients are common to the development of ARF in other conditions. However, ARF may also develop due to etiologies arising from cancer treatment, such as nephrotoxic chemotherapy agents or the disease itself, including post-renal obstruction, compression or infiltration, and metabolic o

Крупная долгосрочная база данных о пациентах, страдающих болезнью Гаучера, свидетельствует о возросшем риске лимфомы и миэломы, но не твердых опухолей.

БОЛЬШЕЕ: Болезнь Гаучера (ГД) во многом связана с риском заболевания раком, причем в литературе содержатся противоречивые сообщения. Понимание истинной проблемы рака имеет решающее значение для ухода за пациентами и генетического консультирования. AIM: Определение общего и специфического риска заболевания раком в большой, одноцентровой группе GD three десятилетиями. МЕТОДЫ: Это ретроспективное когортное исследование, проведенное в национальном справочном центре. Медицинские записи 709 Пожилые пациенты из числа гинекологов >20 В Медицинском центре им. Шаара Зедека был проведен обзор. Раковые ди

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… The introduction of the placental‐derived, macrophage‐targeted enzyme replacement therapy (ERT) in 1991 1 marked a turning point, not only for GD but also for other LSDs and the broader rare disease field. … Enzyme replacement therapy leading to improvement in myeloma indices in a patient with concomitant Gaucher disease . Intern Med J 2022 ; 52 : 872 – 875 . 35538014 10.1111/imj.15781 20 Pavlova EV , Archer J , Wang S , Dekker N , Aerts JM , Karlsson S et al . …

Soluble Biomarkers of Osteoporosis and Osteoarthritis, from Pathway Mapping to Clinical Trials: An Update.

Serum biomarkers of osteoarticular diseases have been in the limelight of current clinical research trends. Laboratory validation of defined and candidate biomarkers for both osteoarthritis and osteoporosis is of key importance for future decisional algorithms in the diagnosis, monitoring, and prognosis of these diseases. The current guidelines recommend the use of collagen degradation remnants, eg, CTX-I and CTX-II, in the complementary diagnosis of both osteoporosis and osteoarthritis. Besides the collagen degradation markers, enzymes that regulate bone and articular metabolism are useful in