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Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.

Background: Alglucerase enzyme replacement therapy was approved for Gaucher disease (GD) in the United States in 1991; imiglucerase in 1994. We report hematologic, visceral, bone pain, bone crisis, height, weight, and Body Mass Index (BMI) outcomes in patients treated for 20 (±3) years with subset analyses based on pre-treatment severity, genotype, and age at treatment initiation., Methods: GD type 1 (GD1) patients in the ICGG Gaucher Registry with complete sets of baseline, 10-year, and 20-year data are included (N = 475). Ten-year and 20-year data are compared to pre-treatment baseline, stratified by splenectomy status., Results: Non-splenectomized patients: Improvements observed at 10 years were maintained at 20 years for most outcomes. Mean changes from baseline at 10 and 20 years, respectively, were: spleen volume: 18.2 multiples of normal (MN) to 5.1 MN and 4.2 MN; liver volume: 1.8 MN to 1.0 MN and 1.0 MN; hemoglobin: 11.4 g/dL to 13.7 g/dL and 13.8 g/dL; platelet count: 91.6 × 10 9 /L to 168.0 × 10 9 /L and 169.1 × 10 9 /L; without bone crisis: 85.0% to 98.2% and 96.5%; without bone pain: 52.5% to 72.0% at 10 years, no significant change at 20 years (58.5%). Splenectomized patients: significant changes were observed in liver volume: 2.3 MN to 1.1 MN and 1.0 MN; hemoglobin: 11.7 g/dL to 13.3 g/dL and 13.4 g/dL; platelet count: 229.1 × 10 9 /L to 288.1 × 10 9 /L and 257.0 × 10 9 /L; without bone crisis: 52.2% to 91.3% and 100%; without bone pain: 16.3% to 30.6% (not significant) and 46.9%. Similar results were found in each of the subset analyses. Patients who start treatment during childhood have normal weight and height in young adulthood. Many treated adult patients are overweight or obese; however, this is consistent with BMI trends observed in the general population. After 1-2 years, the average biweekly imiglucerase dose is ~40 units/kg body weight., Conclusion: Imiglucerase is an effective, long-term treatment for GD1. In a long-term observational setting, improvements seen during early treatment years are sustained by continuing treatment for 20 years, except for bone pain in non-splenectomized patients. These results are consistent when analyzed by different patient subsets, including by disease severity., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

SARS-CoV-2 infection carries high morbidity and mortality in individuals with chronic disorders. Its impact in rare disease populations such as Gaucher disease (GD) is unknown. In GD, decreased acid β-glucosidase activity leads to the accumulation of inflammatory glycosphingolipids and chronic myeloid cell immune activation which a priori could predispose to the most severe effects of SARS-CoV-2. To evaluate the determinants of SARS-CoV-2 infection in GD, we conducted a cross-sectional study in a large cohort. 181 patients were enrolled, including 150 adults and 31 children, with a majority of patients on treatment (78%). Information on COVID-19 exposure, symptoms, and SARS-CoV-2 nucleic acid and/or antibody testing was obtained during the peak of the pandemic in the New York City metropolitan area. Forty-five adults reported a primary exposure to someone with COVID-19 and 17 (38%) of these patients reported at least one COVID-19 symptom. A subset of adults was tested (n = 88) and in this group 18% (16/88) were positive. Patients testing positive for SARS-CoV-2 had significantly more symptoms (4.4 vs 0.3, p < 0.001) than patients testing negative. Among patients who were antibody-positive, quantitative titers indicated moderate to high antibody response. In GD adults, male gender, older age, increased BMI, comorbidities, GBA genotype, prior splenectomy and treatment status were not associated with the probability of reporting symptoms or testing positive. No patient required COVID-19-specific treatments and there were no deaths. Our data suggests that GD does not confer a heightened risk for severe effects of SARS-CoV-2 infection feared based on the known chronic inflammatory state in these patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Lysosomal storage diseases (LSDs) are an individually rare but collectively common group of hereditary, progressive, multi-systemic disorders. Recent technological advances have brought newborn screening (NBS) for LSDs to attention in the United States. However, many LSD symptoms present in later childhood or adulthood, with a wide spectrum of severity. Because late-onset symptoms stray from the traditional NBS model, healthcare providers have expressed concerns about potential harm to patients and/or their families. In this study, 47 individuals with Fabry disease (FD), 22 with Gaucher disease (GD), and 22 with late-onset Pompe disease (LOPD) were surveyed regarding how their life might have been impacted by NBS. Of the 91 participants, none had symptoms at birth and 42 (46.7%) were symptom-free until adulthood. Over half (52.8%) were diagnosed ≥5years from symptom onset; of these, significantly more had FD (60%) or LOPD (63.6%) than GD (23.8%). However, length of diagnostic odyssey was not significantly correlated with opinion on NBS. Most participants either strongly agreed (45%) or agreed (33.3%) with NBS for their condition, with no significant differences between diseases. Opinions on NBS were correlated with participants' opinions on whether NBS would have resulted in better current health, but uncorrelated with disease severity or current life satisfaction. Significantly more participants with FD (42.6%) and LOPD (63.6%) than GD (13.6%) felt they would have greater life satisfaction had they been diagnosed as a newborn (p=0.007). Almost half (41%) of participants would have made different life decisions, including lifestyle, financial, and reproductive decisions. Regarding potential harm, participants were most concerned about insurability and least concerned about removal of children's autonomy. In conclusion, NBS is highly approved of among individuals with LSDs themselves, as it would significantly eliminate diagnostic odysseys and potentially alter life planning., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Clinical care for patients with rare diseases may be complicated by comorbidities. Administration of medications to treat comorbidities may elicit potentially harmful drug-drug interactions (DDIs). Genetic background may also influence DDI occurrence. We investigated the range of comorbid conditions in patients with Gaucher disease type I (GD1), the pharmacotherapies prescribed and the potential for DDI with enzyme replacement and substrate reduction therapies and additional medications, specifically cytochrome P450 (CYP) metabolizing medications., Methods: A literature review examined comorbid conditions and pharmacotherapies reported in GD1. Analysis of two national databases reported real-world prescription practices in patients with GD1 (Germany, N=87; US, N=374). Prescribed drugs were assessed for known interactions with isoenzymes from the hepatic CYP enzyme family., Results: The literature reported GD1 symptomatology and comorbid conditions in broad agreement with the known clinical picture. German patients received 86 different medications whereas US patients received 329 different medications. An average of 3.2 medications (Germany) and 7 medications (US) per patient were prescribed. Moderate/strong inhibitors of CYP isoenzymes were prescribed to 20% and 57% of patients in the US and Germany, respectively., Conclusion: This study describes the extensive number of comorbid conditions and drugs prescribed to patients with GD1, and the importance of determining CYP isoenzyme interaction to reduce DDI risk., (Published by Elsevier Inc.)