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Klin Padiatr 2019; 231(02): 52-59
DOI: 10.1055/a-0788-8795
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Retrospective Analysis of Whole-Body Magnetic Resonance Imaging of Bone Manifestations in Long-Term Treated Patients with Gaucher Disease Type 1

Eine retrospektive Auswertung der Knochenmanifestationen bei langzeitbehandelten Patienten mit M. Gaucher (Typ 1) mittels Ganzkörper-MRT
André Lollert
1   Department of Diagnostic and Interventional Radiology, Section of Pediatric Radiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
Katharina Laudemann
1   Department of Diagnostic and Interventional Radiology, Section of Pediatric Radiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
Eugen Mengel
2   Center of Pediatrics and Adolescent Medicine, Villa Metabolica, Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
Christian Hoffmann
1   Department of Diagnostic and Interventional Radiology, Section of Pediatric Radiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
Larissa Moos
1   Department of Diagnostic and Interventional Radiology, Section of Pediatric Radiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
Jörg Reinke
2   Center of Pediatrics and Adolescent Medicine, Villa Metabolica, Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
Miriam Brixius-Huth
2   Center of Pediatrics and Adolescent Medicine, Villa Metabolica, Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
Julia B. Hennermann
2   Center of Pediatrics and Adolescent Medicine, Villa Metabolica, Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
Christoph Düber
3   Department of Diagnostic and Interventional Radiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
Gundula Staatz
1   Department of Diagnostic and Interventional Radiology, Section of Pediatric Radiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
27 November 2018 (online)

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Abstract

Purpose We retrospectively assessed bone and visceral manifestations in patients with Gaucher disease type 1 (GD1) with whole-body magnetic resonance imaging (WB-MRI) to determine the effects of different timing in initiating long-term enzyme replacement therapy.

Materials and Methods In 17 patients with GD1, we performed 2 WB-MRI examinations at a median interval of 13 months. Patients had received enzyme replacement therapy with alglucerase/imiglucerase for a median of 13 years prior to the first examination. MRI results were retrospectively stratified based on treatment initiation into 2 groups: “early” (age ≤12 years, median 5 years) and “late” (during adulthood, median 32 years). We evaluated occurrence of irreversible avascular necroses (AVN) and applied several semi-quantitative scores, including the Bone-Marrow-Burden (BMB) score, the Düsseldorf-Gaucher score (DGS), the Vertebra-Disc-Ratio (VDR), and the Gaucher disease type 1 Severity Scoring System (GD-DS3).

Results MRI assessments showed no AVN in the “early” group. AVN were observed in 2 patients of the “late” group; one also had a splenic Gaucheroma. The follow-up examinations showed slight improvements in the BMB-score, DGS, and VDR, with similar tendencies in both treatment groups. The GD-DS3 score only improved in “late” group.

Conclusion This retrospective study supported the ongoing clinical value of enzyme replacement therapy with alglucerase/imiglucerase, as WB-MRI-based scores stayed constant or slightly improved even after long-term treatment. Secondary complications were only observed in the late treatment group. Our results suggest that “early initiation” of enzyme replacement therapy may protect the bone.

Zusammenfassung

Ziel Ziel der Arbeit war eine retrospektive Erfassung von Knochen- und viszeralen Komplikationen bei Patienten mit M. Gaucher Typ 1 mittels Ganzkörper-MRT. Insbesondere wurden Unterschiede zwischen Patienten mit frühem und späterem Start der Enzymersatztherapie analysiert.

Material und Methoden Zwei MRT-Untersuchungen (medianes Intervall: 13 Monate) wurden bei 17 Patienten mit M. Gaucher durchgeführt. Die Patienten wurden zuvor langfristig (Median: 13 Jahre) mittels Enzymersatztherapie (Alglucerase/Imiglucerase) behandelt und basierend auf dem Therapiebeginn retrospektiv in 2 Gruppen unterteilt: „früh” (Alter≤12 Jahre, Median 5 Jahre) und „spät“ (im Erwachsenenalter, Median 32 Jahre). Irreversible avaskuläre Nekrosen (AVN) wurden erfasst, zusätzlich wurden semiquantitative Scores erhoben: Bone-Marrow-Burden (BMB) Score, Düsseldorf-Gaucher Score (DGS), Vertebra-Disc-Ratio (VDR) und Gaucher disease type 1 Severity Scoring System (GD-DS3).

Ergebnisse In der Gruppe der Patienten mit „frühem” Therapiebeginn wurden keine AVN nachgewiesen, während solche bei 2 Patienten der „späten“ Therapiegruppe auftraten. Bei einem dieser Patienten war zusätzlich ein Gaucherom der Milz nachweisbar. Die Verlaufsuntersuchung zeigte leichte Verbesserungen im BMB-Score, DGS und der VDR in beiden Gruppen. Der GD-DS3 verbesserte sich nur in der „späten” Gruppe.

Schlussfolgerung Diese retrospektive Studie zeigte den fortlaufenden klinischen Wert einer Langzeitbehandlung mittels Enzymersatztherapie. Sekundärkomplikationen traten nur in der Gruppe mit spätem Therapiebeginn auf. Die Ergebnisse weisen darauf hin, dass ein früher Therapiebeginn den Knochen vor Sekundärschäden bewahren kann.

Key words

Gaucher disease - alglucerase - imiglucerase - enzyme replacement therapy - whole-body MRI

Schlüsselwörter

Morbus Gaucher - Alglucerase - Imiglucerase - Enzymersatztherapie - Ganzkörper-MRT
 

  • References

  • 1 Andersson H, Kaplan P, Kacena K. et al. Eight-year clinical outcomes of long-term enzyme replacement therapy for 884 children with Gaucher disease type 1. Pediatrics 2008; 122: 1182-1190
    CrossrefPubMedSearch in Google Scholar
  • 2 Barton NW, Brady RO, Dambrosia JM. et al. Replacement therapy for inherited enzyme deficiency – macrophage-targeted glucocerebrosidase for Gaucher’s disease. N Engl J Med 1991; 324: 1464-1470
    CrossrefPubMedSearch in Google Scholar
  • 3 Beck M, Vom Dahl S, Mengel E et al. Diagnose und Therapie des Morbus Gaucher. AWMF-Leitlinien-Register 2006
    PubMed
  • 4 Bender R, Lange S, Ziegler A. Multiples Testen. Dtsch Med Wochenschr 2007; 132 (Suppl. 01) e26-e29
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Brady RO, Kanfer J, Shapiro D. The Metabolism of Glucocerebrosides. I. Purification and Properties of a glucocerebroside-cleaving enzyme from spleen tissue. J Biol Chem 1965; 240: 39-43
    CrossrefPubMedSearch in Google Scholar
  • 6 Deegan PB, Pavlova E, Tindall J. et al. Osseous manifestations of adult Gaucher disease in the era of enzyme replacement therapy. Medicine (Baltimore) 2011; 90: 52-60
    PubMedSearch in Google Scholar
  • 7 Elstein D, Haims AH, Zahrieh D. et al. Impact of velaglucerase alfa on bone marrow burden score in adult patients with type 1 Gaucher disease: 7-year follow-up. Blood Cells Mol Dis 2014; 53: 56-60
    CrossrefPubMedSearch in Google Scholar
  • 8 Fedida B, Touraine S, Stirnemann J. et al. Bone marrow involvement in Gaucher disease at MRI: What long-term evolution can we expect under enzyme replacement therapy?. Eur Radiol 2015; 25: 2969-2975
    CrossrefPubMedSearch in Google Scholar
  • 9 Grabowski GA, Barton NW, Pastores G. et al. Enzyme therapy in type 1 Gaucher disease: Comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources. Ann Intern Med 1995; 122: 33-39
    PubMedSearch in Google Scholar
  • 10 Kaplan P, Baris H, Meirleir L. et al. Revised recommendations for the management of Gaucher disease in children. Eur J Pediatr 2013; 172: 447-458
    CrossrefPubMedSearch in Google Scholar
  • 11 Lai JKC, Robertson PL, Goh C. et al. Intraobserver and interobserver variability of the bone marrow burden (BMB) score for the assessment of disease severity in Gaucher disease. Possible impact of reporting experience. Blood Cells Mol Dis 2018; 68: 121-125
    CrossrefPubMedSearch in Google Scholar
  • 12 Laudemann K, Moos L, Mengel KE. et al. Evaluation of Bone Marrow Infiltration in Non-Neuropathic Gaucher Disease Patients with Use of Whole-Body MRI – A Retrospective Data Analysis. Rofo 2015; 187: 1093-1098
    Thieme ConnectPubMedSearch in Google Scholar
  • 13 Laudemann K, Moos L, Mengel E. et al. Evaluation of treatment response to enzyme replacement therapy with Velaglucerase alfa in patients with Gaucher disease using whole-body magnetic resonance imaging. Blood Cells Mol Dis 2016; 57: 35-41
    CrossrefPubMedSearch in Google Scholar
  • 14 Maas M, Hollak CEM, Akkerman EM. et al. Quantification of Skeletal Involvement in Adults with Type I Gaucher’s Disease: Fat Fraction Measured by Dixon Quantitative Chemical Shift Imaging as a Valid Parameter. AJR Am J Roentgenol 2002; 179: 961-965
    CrossrefPubMedSearch in Google Scholar
  • 15 Maas M, van Kuijk C, Stoker J. et al. Quantification of bone involvement in Gaucher disease: MR imaging bone marrow burden score as an alternative to Dixon quantitative chemical shift MR imaging – initial experience. Radiology 2003; 229: 554-561
    CrossrefPubMedSearch in Google Scholar
  • 16 Mikosch P, Hughes D. An overview on bone manifestations in Gaucher disease. Wien Med Wochenschr 2010; 160: 609-624
    CrossrefPubMedSearch in Google Scholar
  • 17 Mistry PK, Deegan P, Vellodi A. et al. Timing of initiation of enzyme replacement therapy after diagnosis of type 1 Gaucher disease: Effect on incidence of avascular necrosis. Br J Haematol 2009; 147: 561-570
    CrossrefPubMedSearch in Google Scholar
  • 18 Piran S, Amato D. Gaucher disease: A systematic review and meta-analysis of bone complications and their response to treatment. J Inherit Metab Dis 2010; 33: 271-279
    CrossrefPubMedSearch in Google Scholar
  • 19 Poll LW, Willers R, Häussinger D. et al. MRT der Knochenmarkverändungen bei 63 Patienten mit Morbus Gaucher Typ I. Rofo 2010; 182: 979-985
    Thieme ConnectPubMedSearch in Google Scholar
  • 20 Poll LW, Cox ML, Godehardt E. et al. Whole body MRI in type I Gaucher patients: Evaluation of skeletal involvement. Blood Cells Mol Dis 2011; 46: 53-59
    CrossrefPubMedSearch in Google Scholar
  • 21 Regenboog M, Bohte AE, Somers I. et al. Imaging characteristics of focal splenic and hepatic lesions in type 1 Gaucher disease. Blood Cells Mol Dis 2016; 60: 49-57
    CrossrefPubMedSearch in Google Scholar
  • 22 Regenboog M, Bohte AE, Akkerman EM. et al. Iron storage in liver, bone marrow and splenic Gaucheroma reflects residual disease in type 1 Gaucher disease patients on treatment. Br J Haematol 2017; 179: 635-647
    CrossrefPubMedSearch in Google Scholar
  • 23 Serratrice C, Carballo S, Serratrice J. et al. Imiglucerase in the management of Gaucher disease type 1: An evidence-based review of its place in therapy. Core Evid 2016; 11: 37-47
    CrossrefPubMedSearch in Google Scholar
  • 24 Stein P, Yu H, Jain D. et al. Hyperferritinemia and iron overload in type 1 Gaucher disease. Am J Hematol 2010; 85: 472-476
    CrossrefPubMedSearch in Google Scholar
  • 25 Stirnemann J, Belmatoug N, Camou F et al. A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. Int J Mol Sci 2017; 18. Pii: E441.
    PubMed
  • 26 Vlieger EJP, Maas M, Akkerman EM. et al. Vertebra Disc Ratio as a Parameter for Bone Marrow Involvement and Its Application in Gaucher Disease. J Comput Assist Tomogr 2002; 26: 843-848
    CrossrefPubMedSearch in Google Scholar
  • 27 Vom Dahl S, Poll L, Di Rocco M. et al. Evidence-based recommendations for monitoring bone disease and the response to enzyme replacement therapy in Gaucher patients. Curr Med Res Opin 2006; 22: 1045-1064
    CrossrefPubMedSearch in Google Scholar
  • 28 Weinreb NJ, Cappellini MD, Cox TM. et al. A validated disease severity scoring system for adults with type 1 Gaucher disease. Genet Med 2010; 12: 44-51
    PubMedSearch in Google Scholar
  • 29 Zimran A. How I treat Gaucher disease. Blood 2011; 118: 1463-1471
    CrossrefPubMedSearch in Google Scholar