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Pediatric non-neuronopathic Gaucher disease: presentation, diagnosis and assessment. Consensus statements

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Abstract

Gaucher disease is caused by defective activity of glucocerebrosidase. The resulting accumulation of glucocerebroside in the lysosomes of visceral macrophages in various tissue and organ compartments leads to multiple manifestations, including hepatosplenomegaly, anemia, thrombocytopenia, growth retardation and skeletal disease. The most prevalent form of Gaucher disease is the non-neuronopathic (type 1) variant, which lacks primary involvement of the central nervous system. Traditionally, this has been referred to as the ‘adult type’; however, 66% of individuals with symptomatic non-neuronopathic Gaucher disease manifest in childhood. Onset in childhood is usually predictive of a severe, rapidly progressive phenotype and children with non-neuronopathic Gaucher disease are at high risk for morbid complications. Enzyme therapy with recombinant human glucocerebrosidase in childhood can restore health in reversible manifestations and prevent the development of irreversible symptoms. A heightened focus on pediatric Gaucher disease is therefore needed. Although some correlation has been found between genotype and phenotype, mutation analysis is of limited value in disease prognosis. Management of pediatric Gaucher disease should be underpinned by a thorough assessment of the phenotype at baseline with regular monitoring thereafter. Excluding neuronopathic disease is recommended as the first step. Subsequently, baseline evaluation should focus on staging of different storage tissues, particularly the bone the involvement of which results in the greatest long-term morbidity. These organ assessments are recommended because bone disease severity may not correlate with disease severity in other organs and vice versa. In addition, different organs may respond differently to therapy. Initial assessment of each organ system can enable setting of realistic and individualized goals. Conclusion: A thorough approach to baseline assessment will improve the understanding of childhood Gaucher disease, optimizing management to minimize impairment of growth and development and prevent irreversible symptoms.

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Abbreviations

QoL :

quality-of-life

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Acknowledgements

This publication was supported through an educational grant from Genzyme Corporation.

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Authors and Affiliations

  1. Division and Program in Human Genetics, Children’s Hospital Research Foundation, Cincinnati, OH 45229-3039, USA

    Gregory A. Grabowski

  2. Department of Pediatrics, Federico II University, Naples, Italy

    Generoso Andria

  3. Department of Pediatrics, Hospital Miguel Servet, Zaragoza, Spain

    Antonio Baldellou

  4. Plymouth Institute of Neuroscience, Plymouth and Great Ormond Street Hospital for Children, London, UK

    Pauline E. Campbell & Chris M. Harris

  5. Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Section of Clinical Genetics, Children’s Memorial Hospital, Chicago, IL, USA

    Joel Charrow

  6. Department of Pediatric Hematology Oncology, Schneider Children’s Medical Center, Sackler School of Medicine, Tel Aviv University, Israel

    Ian J. Cohen

  7. Section of Metabolic Diseases, Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, USA

    Paige Kaplan

  8. Children’s Hospital, Johannes-Gutenberg University, Mainz, Germany

    Eugen Mengel

  9. Department of Biochemistry Molecular and Cellular Biology, University of Zaragoza, Zaragoza, Spain

    Miguel Pocovi

  10. Metabolic Unit, Great Ormond Street Hospital for Children, London, UK

    Ashok Vellodi

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  1. Gregory A. Grabowski
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  2. Generoso Andria
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Correspondence to Gregory A. Grabowski.

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Grabowski, G.A., Andria, G., Baldellou, A. et al. Pediatric non-neuronopathic Gaucher disease: presentation, diagnosis and assessment. Consensus statements. Eur J Pediatr 163, 58–66 (2004). https://doi.org/10.1007/s00431-003-1362-0

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  • DOI: https://doi.org/10.1007/s00431-003-1362-0

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