Acid sphingomyelinase deficiency and Gaucher disease: Underdiagnosed and often treatable causes of hepatomegaly, splenomegaly, and low HDL cholesterol in lean individuals.

Background: Acid sphingomyelinase deficiency (ASMD) and Gaucher disease type 1 (GD1) are rare inherited sphingolipid disorders with multisystemic manifestations, including liver disease and dyslipidemia. Despite effective treatments, insufficient disease awareness frequently results in diagnostic delays during which irreversible complications occur. We delineated the shared and distinctive features of hepatic, splenic, and lipoprotein phenotypes in ASMD and GD1.

The impact of sphingomyelin on the pathophysiology and treatment response to olipudase alfa in acid sphingomyelinase deficiency.

Acid sphingomyelinase deficiency (ASMD) is a rare progressive genetic disorder caused by pathogenic variants in the gene causing low or absent activity of the enzyme acid sphingomyelinase, resulting in subsequent accumulation of its substrate, sphingomyelin. Signs and symptoms of excessive lysosomal sphingomyelin storage, such as hepatosplenomegaly and pulmonary impairment, and in a subset of patients, progressive neurological manifestations, have long been recognized as hallmarks of the disease. Uncontrolled accumulation of sphingomyelin has important and complex downstream metabolic and immunologic consequences that contribute to the disease burden.

Incentivizing Pregnant Women to Quit Smoking in the Real World-A Community-Based Pilot Intervention.

Smoking during pregnancy is a leading preventable cause of poor pregnancy outcomes. Financial incentives interventions yield quit rates of approximately 30% during pregnancy, versus approximately 4% in traditional smoking cessation programs. This pilot study assessed the feasibility of translating an efficacious University of Vermont research-based intervention into a rural community setting delivered by the Vermont Department of Health.

Real-world effectiveness of eliglustat in treatment-naïve and switch patients enrolled in the International Collaborative Gaucher Group Gaucher Registry.

Eliglustat is a first-line oral therapy for adults with Gaucher disease type 1 (GD1) with extensive, intermediate, or poor CYP2D6-metabolizer phenotypes (90% of patients). We report real-world outcomes after 2 years of eliglustat therapy in the International Collaborative Gaucher Group Gaucher Registry (NCT00358943). As of January 2019, baseline and 2-year data (±1 year) were available for 231 eliglustat-treated GD1 patients: 19 treatment-naïve (zero splenectomized) and 212 ERT patients who switched to eliglustat (36 splenectomized).

Long-term adverse event profile from four completed trials of oral eliglustat in adults with Gaucher disease type 1.

Background: Eliglustat is a first-line oral treatment for adults with Gaucher disease type 1 who have an extensive, intermediate or poor CYP2D6 metabolizer phenotype (> 90% of patients). Whereas enzyme replacement therapy for Gaucher disease has been widely used for more than two decades, eliglustat has only been in commercial use since 2014. Clinicians and patients want to better understand which adverse events are most commonly associated with eliglustat, as well as their severity, frequency, and duration.

A pooled analysis of adverse events in 393 adults with Gaucher disease type 1 from four clinical trials of oral eliglustat: Evaluation of frequency, timing, and duration.

Eliglustat, an oral substrate reduction therapy, is a first-line therapy for adults with Gaucher disease type 1 and a compatible CYP2D6 metabolizer phenotype. Clinicians have requested more information about frequency, timing, and duration of adverse events associated with eliglustat. Adverse event data as of January 31, 2013 for all patients who received at least one dose of eliglustat were pooled from four eliglustat clinical trials (393 patients representing 535 patient-years of exposure).

Stability is maintained in adults with Gaucher disease type 1 switched from velaglucerase alfa to eliglustat or imiglucerase: A sub-analysis of the eliglustat ENCORE trial.

Gaucher disease type 1 is an autosomal recessive disorder caused by deficient activity of the lysosomal enzyme acid β-glucosidase resulting in accumulation of glucosylceramide and clinical manifestations of anemia, thrombocytopenia, hepatosplenomegaly, and skeletal disease. The historic standard of care is intravenous recombinant enzyme therapy with imiglucerase. Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 who have a compatible CYP2D6-metabolizer phenotype (≈ 95% of patients).

Clinical response to eliglustat in treatment-naïve patients with Gaucher disease type 1: Post-hoc comparison to imiglucerase-treated patients enrolled in the International Collaborative Gaucher Group Gaucher Registry.

Eliglustat is a recently approved oral therapy in the United States and Europe for adults with Gaucher disease type 1 who are CYP2D6 extensive, intermediate, or poor metabolizers (> 90% of patients) that has been shown to decrease spleen and liver volume and increase hemoglobin concentrations and platelet counts in untreated adults with Gaucher disease type 1 and maintain these parameters in patients previously stabilized on enzyme replacement therapy. In a post-hoc analysis, we compared the results of eliglustat treatment in treatment-naïve patients in two clinical studies with the results of imiglucerase treatment among a cohort of treatment-naïve patients with comparable baseline hematologic and visceral parameters in the International Collaborative Gaucher Group Gaucher Registry. Organ volumes and hematologic parameters improved from baseline in both treatment groups, with a time course and degree of improvement in eliglustat-treated patients similar to imiglucerase-treated patients.

High rate of postoperative mortality in patients with mucopolysaccharidosis I: findings from the MPS I Registry.

Background/purpose: Mucopolysaccharidosis I (MPS I) is a rare lysosomal storage disorder caused by deficiency of α-L-iduronidase, which results in progressive multisystemic disease. Patients with MPS I often require multiple common and uncommon surgeries and are at risk for surgical and anesthetic complications because of respiratory and cardiac disease. Surgery often precedes diagnosis; thus, surgeons and anesthesiologists may be unaware of potential risks.

Diagnosis and treatment trends in mucopolysaccharidosis I: findings from the MPS I Registry.

Unlabelled: Our objective was to assess how the diagnosis and treatment of mucopolysaccharidosis I (MPS I) have changed over time. We used data from 891 patients in the MPS I Registry, an international observational database, to analyze ages at symptom onset, diagnosis, treatment initiation, and treatment allocation (hematopoietic stem cell transplantation, enzyme replacement therapy with laronidase, both, or neither) over time for all disease phenotypes (Hurler, Hurler-Scheie, and Scheie syndromes). The interval between diagnosis and treatment has become shorter since laronidase became available in 2003 (gap during 2006-2009: Hurler--0.

Diagnosis of the mucopolysaccharidoses.

The mucopolysaccharidoses (MPSs) often present a diagnostic challenge, particularly for patients who have more slowly progressive disease phenotypes, as early disease manifestations can be subtle or non-specific. However, certain types of bone and joint involvement should always prompt consideration of an MPS diagnosis, such as early joint involvement without classic inflammatory features or erosive bone lesions, claw hand, spinal deformities or dysostosis multiplex. All such patients should be referred to a geneticist or metabolic specialist for diagnostic evaluation.

Characterization of surgical procedures in patients with mucopolysaccharidosis type I: findings from the MPS I Registry.

Objective: To clarify the extent and chronology of surgical burden in relation to symptom onset and diagnosis in patients with mucopolysaccharidosis I (MPS I) as reported in the MPS I Registry, an international observational database.

Study Design: Analysis of surgical data from 544 patients enrolled in the MPS I Registry. Among all patients with at least 1 reported surgery, the number and frequency of procedures, and age at procedure, diagnosis, and symptom onset were collected overall, by patient, and by reported phenotype (Hurler, Hurler-Scheie, Scheie).