Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease

Biegstraaten, Marieke; Cox, Timothy M.; Belmatoug, Nadia; Berger, Marc; Collin-Histed, Tanya; Dahl, Stephan Vom; Rocco, Maja Di; Fraga, Cristina; Giona, Fiorina; Giraldo, Pilar; Hasanhodžić, Mensuda; Hughes, D.A.; Iversen, Per Ole; Kiewiet, A.I.; Lukina, Elena; Machaczka, Maciej; Marinakis, Theodore; Mengel, Eugen; Pastores, Gregory M.; Plöckinger, Ursula; Rosenbaum, Hanna; Serratrice, J.; Symeonidis, Argiris; Szer, Jeff; Timmerman, J.; Tylki‐Szymańska, Anna; Hubshman, Monika Weisz; Zafeiriou, Dimitrios I.; Zimran, Ari; Hollak, Carla E. M.

doi:10.1016/j.bcmd.2016.10.008

Cited by 90 publications

(69 citation statements)

References 26 publications

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“…These thresholds, which were developed based on real‐world clinical outcomes data from the International Collaborative Gaucher Group Gaucher Registry, are aimed primarily at alleviating florid disease manifestations of anemia, thrombocytopenia, hepatosplenomegaly, skeletal pathology, and impaired growth (in children). Recently, a consensus panel of experts, with input from patients, developed a revised set of management guidelines that expands upon these parameters to include improvement in patient‐reported outcomes, such as quality of life, fatigue and social participation, as well as refractory elements of Gaucher disease, complications, and co‐morbidities . The thresholds for improvement in hemoglobin and hepatosplenomegaly remain essentially unchanged; whereas the platelet goal for nonsplenectomized patients was lowered from ≥120 × 10 9 /L (achieved by 63% of patients in our study) to ≥100 × 10 9 /L (achieved by 74% of patients in our study).…”

Section: Discussionmentioning

confidence: 85%

Outcomes after 8 years of eliglustat therapy for Gaucher disease type 1: Final results from the Phase 2 trial

Lukina

Watman

Dragosky³

et al. 2018

American J Hematol

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Eliglustat is a first‐line oral therapy for adults with Gaucher disease type 1 (GD1) and poor, intermediate or extensive CYP2D6‐metabolizer phenotypes (>90% of patients). We report the final results of a Phase 2 trial and extension (NCT00358150) in previously untreated adult GD1 patients who had splenomegaly with thrombocytopenia and/or anemia and received 50 or 100 mg eliglustat tartrate (equivalent to 42 or 84 mg eliglustat) twice daily for 8 years. In total, 19 of 26 patients completed the trial. After 8 years of eliglustat, mean spleen and liver volumes decreased by 69% and 34%, respectively. Mean hemoglobin concentration and platelet count increased by 2.2 g/dL and 113%, respectively. All patients met at least 3 of 4 therapeutic goals established for patients on long‐term enzyme replacement therapy. Mean final values for patients with severe splenomegaly (n = 6), moderate‐to‐severe anemia (n = 6), or severe thrombocytopenia (n = 8) were similar to patients with milder disease at baseline and within long‐term therapeutic goal thresholds. Biomarker median percent changes from baseline were ‐91% for chitotriosidase, ‐87% for CCL18, ‐92% for glucosylsphingosine, and ‐80% for plasma glucosylceramide. Mean lumbar spine T‐score increased by 0.96, moving from the osteopenic to the normal range. Mean quality‐of‐life scores, mostly below normal at baseline, moved into ranges seen in healthy adults. Eliglustat was well‐tolerated; 98% of adverse events were mild or moderate and 94% were considered unrelated to treatment. Clinically meaningful improvements in all parameters continued or were maintained over 8 years, with the largest margins of improvement seen in the most severely affected patients.

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Section: Discussionmentioning

confidence: 85%

Outcomes after 8 years of eliglustat therapy for Gaucher disease type 1: Final results from the Phase 2 trial

Lukina

Watman

Dragosky³

et al. 2018

American J Hematol

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“…There is currently no cure for GD. Enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) are established therapies (Biegstraaten et al, ). ERTs are administered intravenously on an alternate‐week basis, while SRTs are typically administered orally.…”

Section: Introductionmentioning

confidence: 99%

“…ERTs are administered intravenously on an alternate‐week basis, while SRTs are typically administered orally. The SRT eliglustat was recently approved as a first‐line treatment for adults with GD1 (Biegstraaten et al, ). Both ERTs and SRTs require lifelong treatment.…”

Section: Introductionmentioning

confidence: 99%

Quality of life and psychological functioning of pediatric and young adult patients with Gaucher disease, type 1

Alioto

Gomez

Moses

et al. 2020

American J of Med Genetics Pt A

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This study examined the health-related quality of life (HRQoL) and psychological functioning of children and young adults with Gaucher disease, type 1 (GD1). Thirty-two (17 pediatric, 15 young adult) patients with GD1 and one parent completed ageappropriate assessments of HRQoL, emotional, and behavioral health. The HRQoL of children with GD1 was compared with a healthy sample and to children diagnosed with Fabry disease (FD; another lysosomal storage disease), while young adults were compared to a healthy sample and to patients with self-reported chronic illnesses. Children with GD1 reported significantly lower HRQoL across all domains relative to healthy counterparts yet comparable HRQoL compared to children with FD. Young adults reported mildly lower physical functioning than healthy peers, but no differences in HRQoL relative to the chronic illness sample. Parent-reported symptom severity was associated with poorer HRQOL in children but not young adults. Few group differences in psychological functioning were observed, except young children showed more school problems than the normative average and there was a trend toward internalizing symptoms. Overall, results consistently identified younger patients with GD1 as more affected than older patients in HRQoL and psychological domains. Implementation of psychosocial interventions may be particularly beneficial during early childhood. K E Y W O R D SGaucher disease, health-related quality of life, inborn error of metabolism, pediatric, psychological functioning

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“…This case was challenging since the classical hematological signs of GD were initially mild and incomplete (normal Hb, barely detectable thrombocytopenia and splenomegaly). Over the 15 years follow‐up, the platelet count dropped and the patient developed severe and symptomatic bone marrow infiltration, justifying the starting of ERT . Regarding hyperferritinemia, it was initially attributed to metabolic syndrome, and improvement of lifestyle was recommended.…”

Section: Case Presentationmentioning

confidence: 99%

Hyperferritinemia and diagnosis of type 1 Gaucher disease

et al. 2020

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A 61-year-old Caucasian man presented with persistent hyperferritinemia known since his forties in the presence of components of metabolic syndrome. History revealed longstanding obesity, with maximum weight and BMI of 100 kg and 32 kg/m 2 , respectively. At the age of 45 years, routine blood examination showed marked hyperferritinemia (1738 μg/L) with normal transferrin saturation (TSat 41%), very mild thrombocytopenia (140 × 10 9 /L), normal Hb (139 g/L) and white blood cell count (8.93 × 10 9 /L), and polyclonal hypergammaglobulinemia (21.5%). He also had low HDL cholesterol (0.8 mmol/L), mild hypertriglyceridemia (2.33 mmol/L), impaired fasting glucose (5.66 mmol/L), and oral glucose tolerance test (OGTT) consistent with glucose intolerance (glucose 9.49 mmol/L at 2 hours). Liver function tests were normal, as well as C-reactive protein, coagulation, renal and thyroid function tests. At that time, he reported an unbalanced diet with moderate alcohol consumption, sedentariness, and positive family history for type 2 diabetes mellitus. Abdominal ultrasonography (US) showed mild liver enlargement with increased echogenicity consistent with moderate steatosis; the major diameter of the spleen was 12.4 cm; no signs of portal hypertension were detected. Liver biopsy demonstrated micro-macrovesicular steatosis in 50% of hepatocytes, and hypertrophic Kupffer cells with mild siderosis (Figure 1). A first-level genetic test for HFE-hemochromatosis was negative, only showing heterozygosity for the H63D variant. Sequencing of the SLC40A1 gene (encoding ferroportin) did not reveal pathogenic mutations. A provisional diagnosis of dysmetabolic iron overload syndrome (DIOS) was suggested, and lifestyle changes as well as alcohol withdrawal were recommended.Initially, Gaucher disease (GD) was not suspected. The patient had ≥2 alterations of the metabolic syndrome, liver steatosis and normal TSat, fitting the criteria for the diagnosis of DIOS, 1 which represents a far more frequent cause of hyperferritinemia than GD. A possible Ferroportin Disease, suggested by iron accumulation in Kupffer cells, 2 was ruled out by SLC40A1 sequencing.In the following 15 years, the patient lost weight (8 kg, leading to BMI reduction to 28 kg/m 2 ), and substantially improved his metabolic profile (fasting glucose 4.88 mmol/L, OGTT normalization, HDL cholesterol 1.39 mmol/L, triglycerides 0.93 mmol/L); he also underwent irregular phlebotomies (total n = 12). Nonetheless, serum ferritin was only mildly reduced (1056 μg/L). Of note, hypergammaglobulinemia (21%) was confirmed, and platelet count further decreased § Alberto Piperno and Domenico Girelli equally contributed to the work.

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Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease

Cited by 90 publications

References 26 publications

Outcomes after 8 years of eliglustat therapy for Gaucher disease type 1: Final results from the Phase 2 trial

Outcomes after 8 years of eliglustat therapy for Gaucher disease type 1: Final results from the Phase 2 trial

Quality of life and psychological functioning of pediatric and young adult patients with Gaucher disease, type 1

Hyperferritinemia and diagnosis of type 1 Gaucher disease

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