Presenting signs and patient co-variables in Gaucher disease: outcome of the Gaucher Earlier Diagnosis Consensus (GED-C) Delphi initiative

Atul Mehta; David J Kuter; Sam S Salek; Nadia Belmatoug; Bruno Bembi; Jeremy Bright; Stephan Vom Dahl; Federica Deodato; Maja Di Rocco; Ozlem Göker-Alpan; Derralynn A Hughes; Elena A Lukina; Maciej Machaczka; Eugen Mengel; Aabha Nagral; Kimitoshi Nakamura; Aya Narita; Beatriz Oliveri; Gregory Pastores; Jordi Pérez-López; Uma Ramaswami; Ida V Schwartz; Jeff Szer; Neal J Weinreb; Ari Zimran

doi:10.1111/imj.14156

Presenting signs and patient co-variables in Gaucher disease: outcome of the Gaucher Earlier Diagnosis Consensus (GED-C) Delphi initiative

Intern Med J. 2019 May;49(5):578-591. doi: 10.1111/imj.14156.

Authors

Atul Mehta¹, David J Kuter², Sam S Salek³, Nadia Belmatoug⁴, Bruno Bembi⁵, Jeremy Bright⁶, Stephan Vom Dahl⁷, Federica Deodato⁸, Maja Di Rocco⁹, Ozlem Göker-Alpan¹⁰, Derralynn A Hughes¹, Elena A Lukina¹¹, Maciej Machaczka^{12

13}, Eugen Mengel¹⁴, Aabha Nagral^{15

16}, Kimitoshi Nakamura¹⁷, Aya Narita¹⁸, Beatriz Oliveri¹⁹, Gregory Pastores²⁰, Jordi Pérez-López²¹, Uma Ramaswami¹, Ida V Schwartz²², Jeff Szer²³, Neal J Weinreb²⁴, Ari Zimran^{25

26}

Affiliations

¹ Lysosomal Storage Disorders Unit, Department of Haematology, Royal Free Hospital, UCL Medical School, London, UK.
² Center for Hematology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³ School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK.
⁴ Referral Center for Lysosomal Diseases, University Hospital Paris Nord Val de Seine, site Beaujon, Clichy, Paris, France.
⁵ Centre for Rare Diseases, Academic Medical Centre Hospital of Udine, Udine, Italy.
⁶ Research Evaluation Unit, Oxford PharmaGenesis Ltd, Oxford, UK.
⁷ Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine University, Düsseldorf, Germany.
⁸ Division of Metabolism, Department of Pediatric Specialist, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁹ Unit of Rare Diseases, Department of Pediatrics, IRCCS Giannina Gaslini Institute, Genoa, Italy.
¹⁰ Lysosomal Disorders Unit and CFCT, O and O Alpan LLC, Fairfax, Virginia, USA.
¹¹ Department of Orphan Diseases, National Research Center for Hematology, Moscow, Russia.
¹² Medical Faculty, University of Rzeszow, Rzeszow, Poland.
¹³ Department of Medicine at Huddinge, Hematology Center Karolinska, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
¹⁴ Villa Metabolica, Center of Pediatric and Adolescent Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
¹⁵ Department of Gastroenterology, Jaslok Hospital and Research Centre, Mumbai, India.
¹⁶ Department of Gastroenterology, Apollo Hospital, Mumbai, India.
¹⁷ Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
¹⁸ Department of Child Neurology, Faculty of Medicine, Tottori University, Yon ago, Japan.
¹⁹ Osteoporosis and Metabolic Bone Diseases Laboratory, Institute of Immunology, Genetics, and Metabolism (INIGEM) CONICET - UBA, Buenos Aires, Argentina.
²⁰ University College Dublin, The Mater Misericordiae University Hospital, Dublin, Ireland.
²¹ Unit of Rare Diseases, Hospital Vall d'Hebron, Barcelona, Spain.
²² Medical Genetics Service - HCPA, Genetics Department, UFRGS, Porto Alegre, Brazil.
²³ Department of Clinical Haematology, Bone Marrow Transplant Service, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
²⁴ Department of Human Genetics and Medicine (Hematology), University of Miami Miller School of Medicine, UHealth Sylvester Coral Springs, Coral Springs, Florida, USA.
²⁵ Shaare Zedek Medical Center and Hadassah Medical School, Jerusalem, Israel.
²⁶ Hadassah Medical School, Jerusalem, Israel.

Abstract

Background: Gaucher disease (GD) presents with a range of signs and symptoms. Physicians can fail to recognise the early stages of GD owing to a lack of disease awareness, which can lead to significant diagnostic delays and sometimes irreversible but avoidable morbidities.

Aim: The Gaucher Earlier Diagnosis Consensus (GED-C) initiative aimed to identify signs and co-variables considered most indicative of early type 1 and type 3 GD, to help non-specialists identify 'at-risk' patients who may benefit from diagnostic testing.

Methods: An anonymous, three-round Delphi consensus process was deployed among a global panel of 22 specialists in GD (median experience 17.5 years, collectively managing almost 3000 patients). The rounds entailed data gathering, then importance ranking and establishment of consensus, using 5-point Likert scales and scoring thresholds defined a priori.

Results: For type 1 disease, seven major signs (splenomegaly, thrombocytopenia, bone-related manifestations, anaemia, hyperferritinaemia, hepatomegaly and gammopathy) and two major co-variables (family history of GD and Ashkenazi-Jewish ancestry) were identified. For type 3 disease, nine major signs (splenomegaly, oculomotor disturbances, thrombocytopenia, epilepsy, anaemia, hepatomegaly, bone pain, motor disturbances and kyphosis) and one major co-variable (family history of GD) were identified. Lack of disease awareness, overlooking mild early signs and failure to consider GD as a diagnostic differential were considered major barriers to early diagnosis.

Conclusion: The signs and co-variables identified in the GED-C initiative as potentially indicative of early GD will help to guide non-specialists and raise their index of suspicion in identifying patients potentially suitable for diagnostic testing for GD.

Keywords: algorithm; inborn error; lysosomal storage disease; metabolism; splenomegaly; thrombocytopenia.

Publication types

Review

MeSH terms

Consensus*
Delphi Technique*
Early Diagnosis
Gaucher Disease / diagnosis*
Gaucher Disease / physiopathology
Humans
Physicians / standards*

Grants and funding

CME-GBR-12915 and IME-GBR-1439/Shire International GmbH (independent educational grant)/International