BACKGROUND Gaucher disease (GD) is the most common lysosomal storage disorder caused by glucocerebrosidase deficiency. Type 1 GD (GD1) often presents with nonspecific manifestations, including splenomegaly, cytopenias, growth impairment, and skeletal involvement, leading to delayed diagnosis and irreversible complications. This report highlights the delayed diagnosis of GD1 in a patient with longstanding mild manifestations and emphasizes the importance of considering GD in patients with unexplained cytopenias and splenomegaly. CASE REPORT We describe a male patient with GD1 whose first manifestations appeared in infancy and included splenomegaly. During childhood, persistent cytopenias, hepatosplenomegaly, and growth deceleration were observed; however, the diagnosis remained unrecognized. At age 14, the patient developed severe skeletal pain accompanied by fever, prompting further diagnostic evaluation. Imaging studies revealed bone marrow abnormalities, and bone biopsy demonstrated foamy macrophages but did not establish a definitive diagnosis. At age 15, GD1 was suspected and subsequently confirmed by enzymatic testing, biomarker assessment, and genetic analysis. Enzyme replacement therapy with imiglucerase resulted in clinical improvement, reduced organomegaly, and stabilization of laboratory parameters. The patient subsequently underwent a structured transition from pediatric to adult care without treatment interruption. CONCLUSIONS GD should be considered in patients with unexplained splenomegaly and persistent cytopenias, even when early manifestations are mild and nonspecific. Early recognition and disease-specific diagnostic testing may reduce diagnostic delay, facilitate timely treatment initiation, and help prevent irreversible complications. This case also highlights the importance of a structured transition from pediatric to adult care in maintaining long-term treatment continuity.

N-glycosylation, particularly terminal mannose exposure, is a critical quality attribute affecting macrophage targeting and the clinical efficacy of enzyme replacement therapy for Gaucher disease. This study developed a universal, sensitive, and quantitative method to compare the N-glycan profiles of three recombinant human glucocerebrosidase products from different expression systems: imiglucerase, velaglucerase alfa, and velaglucerase beta. Using 2-aminobenzamide labeling combined with HILIC-UPLC-FLD and high-resolution mass spectrometry, an N-glycan profiling platform was established. A multidimensional calibration system integrating retention time, glucose unit values, and mass-to-charge ratios was constructed, and collision-induced dissociation tandem MS was used to identify isomers and phosphorylated glycans. The method showed good specificity, linearity, precision, and accuracy. Glycan profiling revealed clear product-dependent differences: imiglucerase was enriched in core-fucosylated Man3 structures, velaglucerase alfa was dominated by Man9 and contained more phosphorylated and sialylated glycans, whereas velaglucerase beta showed a highly homogeneous Man5 profile. These findings demonstrate how distinct manufacturing strategies shape glycosylation patterns and provide a basis for biosimilar development and comparability assessment.

Gaucher disease is a rare inherited disorder caused by a deficiency of the lysosomal enzyme β-glucocerebrosidase, leading to the accumulation of glucocerebroside within macrophages. This accumulation results in a wide spectrum of clinical manifestations, which may be life-threatening in severe cases. We report the first documented case in Senegal of a patient with Gaucher disease successfully treated with enzyme replacement therapy. The diagnosis was established based on characteristic bone marrow findings showing Gaucher cells, together with markedly reduced β-glucocerebrosidase activity and elevated chitotriosidase levels. The disease was diagnosed at the age of 11 years, and regular intravenous enzyme replacement therapy was initiated. Treatment was well tolerated and resulted in significant clinical improvement and a marked enhancement in the patient's quality of life. However, genetic confirmation by GBA1 mutation analysis could not be performed due to limited access to molecular testing, which represents an important limitation of this report and prevented precise molecular classification of the disease. This case highlights the importance of early diagnosis and timely initiation of enzyme replacement therapy to prevent severe complications in Gaucher disease. Long-term follow-up studies remain necessary to further evaluate the efficacy and safety of enzyme replacement therapy in this setting.

BACKGROUND: Gaucher disease (GD) in children is highly heterogeneous, severe, and particularly devastating in GD type 3 (GD3), which has systemic and neurological involvement. Imiglucerase enzyme replacement therapy is well-established for managing hematovisceral and skeletal manifestations in GD type 1 (GD1). Its long-term impact in GD3 remains underexplored, with evidence limited to small, single-center cohorts and one registry analysis with limited follow-up. METHODS: This longitudinal analysis used data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry as of January 2023. Children diagnosed with GD1 or GD3 who started imiglucerase before age 18 years and had an intact spleen and at least one baseline and follow-up measurement were included. Linear mixed models were used to evaluate long-term treatment response of hemoglobin, platelet count, liver and spleen volumes, and Z-scores for height, weight, body mass index, and total lumbar spine bone mineral density (BMD). RESULTS: In total, 961 children with GD1 and 236 with GD3 met the inclusion criteria, representing a population with severe disease requiring early imiglucerase therapy at a median age (25th, 75th percentile) of 7.8 (4.3, 12.0) years for GD1 and 1.9 (1.4, 3.4) years for GD3. Significant hematological and visceral improvements were observed within the first 1.5 years of treatment (p < 0.001 for all parameters), followed by incremental gains during up to two decades. Height Z-scores increased substantially during the first three years of treatment (p < 0.001). Total lumbar spine BMD Z-scores improved (p < 0.05). CONCLUSIONS: This is the largest, most comprehensive global evaluation of long-term imiglucerase therapy in pediatric GD1 and GD3. Despite complex disease burden in GD3, imiglucerase therapy led to marked hematovisceral disease reversal and meaningful growth improvements, closely paralleling responses in GD1. These findings emphasize the importance of early diagnosis and sustained treatment to optimize long-term outcomes. REGISTRATION (REGISTRY): NCT00358943 (registration date: April 1, 1991). CLINICAL TRIAL: Not applicable.

Untreated women with Gaucher disease (GD) are at an increased risk of GD-related complications during pregnancy. Enzyme replacement therapy with imiglucerase is effective at improving hematologic, visceral, and bone manifestations of GD, and the Food & Drug Administration prescribing information supports that imiglucerase is not associated with adverse maternal or fetal outcomes when used during pregnancy. This study population included women with GD enrolled in the International Collaborative Gaucher Group Gaucher Registry (NCT00358943) Pregnancy Sub-Registry who were treated with imiglucerase during at least one pregnancy as of October 2023. We describe frequency of pregnancy outcomes, birth outcomes, and maternal and neonatal complications. Imiglucerase exposure was reported in 110 pregnancies in 68 women with GD type 1; 68% of pregnancies were exposed during all three trimesters. Of 104 fetuses with reported data, 92 were live births (88.5%), eight were spontaneous abortions (7.7%), and four were elective/therapeutic terminations (3.8%); no stillbirths (> 20 weeks gestation) were reported. The majority of infants (80 of 85 [94.1%]) were born at term. Among 108 pregnancies with data, maternal pregnancy, labor and delivery, and post-partum complications were reported for 33 (30.6%), 26 (24.1%), and 24 (22.2%) pregnancies, respectively, with anemia, thrombocytopenia, and vaginal bleeding among the most prevalent complications. Among 74 infants with data, neonatal complications were reported for seven infants (9.5%). Most pregnancies to women with GD treated with imiglucerase resulted in live births and healthy infants, with risk of spontaneous abortions similar to that of the general population (12%-18%).

Taliglucerase alfa is a biosynthetic synthetic enzyme closely related to beta-glucocerebrosidase, which is a normal component of human milk. Because it is a large protein molecule with a molecular weight of about 61,000, the amount in milk is likely to be very low and absorption is unlikely because it is probably destroyed in the infant's gastrointestinal tract.[1,2] A limited amount of data support the safety of breastfeeding with alglucerase (the placenta-derived form of the enzyme) and imiglucerase (another biosynthetic form of the enzyme). An international panel of clinicians from 9 centers that treat Gaucher's disease reported that, breastfeeding complications were less frequent in mothers who were treated with alglucerase or imiglucerase postpartum than in untreated mothers with Gaucher's disease. Consider limiting the duration of breastfeeding to about 6 months to avoid excessive bone loss in the nursing mother.[2,3]

BACKGROUND: Gaucher disease (GD) is a rare autosomal recessive genetic disorder. The clinical manifestations can be adequately managed with enzyme replacement therapy (ERT). The aim of this systematic literature review was to explore the safety and efficacy or effectiveness (depending on the type of evidence) profile of velaglucerase alfa in the treatment of paediatric patients with type 1 (GD1) and type 3 (GD3) GD across all paediatric ages. METHODS: A systematic review of the PubMed/Medline and Embase databases, along with communications from international conferences, was conducted. The inclusion criteria comprised clinical studies published in either English or Spanish that assessed the therapeutic profile of velaglucerase alfa in patients with GD1 (primarily) and GD3 (exploratorily) of all paediatric ages (0–18 years). For each of the selected publications, data regarding the safety and efficacy/effectiveness of this treatment were extracted. RESULTS: A total of 539 publications were identified, of which 23 studies encompassing data from 159 paediatric patients were included. Nine studies (71 patients) provided information about the safety in paediatric patients with GD1, describing it as well tolerated. Regarding the efficacy/effectiveness, 14 articles (113 patients) reported relevant data for the same subpopulation. Overall, improvements in haematological, visceral, skeletal, biomarker and health-related quality-of-life outcomes have been described in treatment-naïve paediatric patients with GD1 who were initially treated with velaglucerase alfa, as well as maintained stability in patients previously treated with imiglucerase. Furthermore, it has been reported that the safety and efficacy/effectiveness profile administered as home therapy enhances the quality of life for both patients and caregivers. The use of velaglucerase alfa in paediatric patients with GD3 was described in 7 publications (26 patients), suggesting a favourable safety profile, whereas its efficacy/effectiveness was reported in 5 articles (16 patients). Improvements in the non-neurological manifestations of the disease were recorded in patients with GD3. CONCLUSION: This systematic review summarizes the limited evidence on velaglucerase alfa in paediatric patients with GD. Findings suggest that velaglucerase alfa may be a beneficial option for GD1 across all paediatric age groups (0–18 years). Additionally, it might be considered a therapeutic option for non-neurological GD3 symptoms, although evidence is scarce and exploratory, highlighting the need for further research in those patients.

Inconsistent conclusions on the cellular uptake of recombinant human β-glucocerebrosidase (rhGCase) for Gaucher disease stem from a fundamental limitation of existing methods: their inability to generate complete and reliable dose-response curves. This critical flaw, stemming from susceptibility to various experimental variables, prevents accurate potency comparison across different rhGCase products. To address this, we developed a robust bioassay using CHO-K1 cells stably expressing the human macrophage mannose receptor (hMMR). Our method quantifies uptake by measuring the enzymatic activity of internalized rhGCase and consistently produces a classic sigmoidal dose-response curve. Comprehensive validation and mechanistic studies, including inhibition experiments with mannose, fucose, and mannose-6-phosphate, confirmed that uptake is specifically mediated by hMMR, with successful enzyme transport to endosomes/lysosomes. Applying this assay to three commercial products yielded results contrary to prior literature: imiglucerase demonstrated superior uptake activity to velaglucerase alfa. The proposed method represents a significant improvement over existing assays, providing a more accurate and reproducible means to evaluate cellular uptake bioactivity, which is crucial for the quality control of rhGCase therapeutics.

Background/Objectives: Gaucher disease type 1 is an autosomal recessive lysosomal storage disorder caused by pathogenic variants in the GBA1 gene. Although enzyme replacement therapy has improved patient outcomes, there is limited long-term real-world data on taliglucerase alfa. This study aimed to evaluate the long-term efficacy and safety of taliglucerase alfa in both treatment-naïve and previously treated patients with Gaucher disease type 1 over a 10-year period. Methods: This prospective, single-centre cohort study involved 29 patients (13 treatment-naïve and 16 previously treated with imiglucerase) who received taliglucerase alfa from 2015 to 2024. Clinical, hematological, visceral, skeletal, and biochemical parameters were assessed at baseline and at 12, 60, and 120 months. Biomarkers included chitotriosidase and glucosylsphingosine. Safety was evaluated through adverse event reporting and anti-drug antibody testing. Results: Hemoglobin and platelet counts improved or remained stable in all patients. By 60 months, liver volume had normalised in treatment-naïve patients (mean reduction: 23.1%), while spleen volume had decreased by up to 47.3%. Lyso-Gb1 levels decreased by 86.1% in patients who had not previously received treatment and by 59.5% overall, with a strong correlation to adherence. Bone mineral density improved in most cases. 137 adverse events were reported, 24% of which were mild infusion-related reactions. Anti-drug antibody developed in two patients, including one with a reduced therapeutic response. Conclusions: Taliglucerase alfa offers sustained long-term clinical, hematological and biochemical benefits in both treatment-naïve and previously treated Gaucher disease type 1 patients, with a favorable safety profile. Glucosylsphingosine proved to be a highly sensitive biomarker for monitoring therapeutic efficacy and detecting treatment response.

Enzyme replacement therapy (ERT) for Gaucher disease (GD) effectively prevents skeletal, visceral, and hematologic complications of this inherited, lysosomal storage disorder. Taliglucerase is one of the three commercially available ERT products and became the recommended first-line therapy in Québec, Canada in 2016. Thus, 19 patients were switched from imiglucerase to taliglucerase, but more than a quarter experienced significant side effects. Here, we summarize these patients' clinical course and describe 6 suspected product-related adverse-effects.

A 2-year-old patient was admitted to our hospital with hepatosplenomegaly as the prominent clinical feature. Peripheral blood analysis during hospitalization revealed trilineage cytopenia. Bone marrow cytology examination demonstrated abundant suspected Gaucher cells. Full-spine MRI exhibited widening of the distal femoral metaphysis with an "Erlenmeyer flask deformity." Subsequent enzymatic and genetic evaluations for Gaucher disease (GD) confirmed reduced β-glucocerebrosidase (GBA) activity, significantly elevated glucosylsphingosine (Lyso-Gb1) levels, and a homozygous missense mutation in the GBA gene c. 1448T>C(p.Leu483Pro). Genetic testing of the parents revealed both were heterozygous carriers of the same mutationc. 1448T>C(p.Leu483Pro), confirming the diagnosis of GD in the child with an autosomal recessive inheritance pattern. GD typically presents in childhood with hepatosplenomegaly, anemia, and thrombocytopenia. Given its rarity and nonspecific clinical manifestations, bone marrow cytology and imaging studies may provide diagnostic clues, but definitive diagnosis requires confirmation through β-glucocerebrosidase activity assays and genetic testing. Enzyme replacement therapy (ERT) is currently the primary treatment modality. The child is receiving regular intravenous infusions of imiglucerase at our hospital.