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Original research
Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency
  1. Abdellah Tebani1,2,
  2. Bénédicte Sudrié-Arnaud1,
  3. Ivana Dabaj2,3,
  4. Stéphanie Torre3,
  5. Laur Domitille4,
  6. Sarah Snanoudj1,2,
  7. Benedicte Heron5,
  8. Thierry Levade6,7,
  9. Catherine Caillaud8,
  10. Sabrina Vergnaud9,
  11. Pascale Saugier-Veber2,
  12. Sophie Coutant10,
  13. Hélène Dranguet1,
  14. Roseline Froissart11,
  15. Majed Al Khouri12,
  16. Yves Alembik13,
  17. Julien Baruteau14,
  18. Jean-Baptiste Arnoux15,
  19. Anais Brassier16,
  20. Anne-Claire Brehin2,
  21. Tiffany Busa17,
  22. Aline Cano18,
  23. Brigitte Chabrol18,
  24. Christine Coubes19,
  25. Isabelle Desguerre20,
  26. Martine Doco-Fenzy21,22,
  27. Bernard Drenou23,
  28. Nursel H Elcioglu24,
  29. Solaf Elsayed25,
  30. Alain Fouilhoux26,
  31. Céline Poirsier27,
  32. Alice Goldenberg10,
  33. Philippe Jouvencel28,
  34. Alice Kuster29,
  35. François Labarthe30,
  36. Leila Lazaro28,
  37. Samia Pichard31,
  38. Serge Rivera28,
  39. Sandrine Roche32,
  40. Stéphanie Roggerone33,
  41. Agathe Roubertie34,35,
  42. Sabine Sigaudy36,
  43. Marta Spodenkiewicz27,
  44. Marine Tardieu37,
  45. Catherine Vanhulle3,
  46. Stéphane Marret2,3,
  47. Soumeya Bekri2,38
  1. 1 Department of Metabolic Biochemistry, Rouen University Hospital, Rouen, France
  2. 2 Normandie Univ, UNIROUEN, CHU Rouen, INSERM U1245, 76000 Rouen, Normandy Center for Genomic and Personalized Medicine, Rouen, France
  3. 3 Department of Neonatal Pediatrics, Intensive Care and Neuropediatrics, Rouen University Hospital, Rouen, France
  4. 4 Pediatric Neurology Department, Robert Debré Hospital, Public Hospital Network of Paris, Paris, France
  5. 5 Reference Center for Lysosomal Diseases, Pediatric Neurology Department, UH Armand Trousseau-La Roche Guyon, APHP, GUEP, Paris, France
  6. 6 Laboratoire de Biochimie Métabolique, Institut Fédératif de Biologie, CHU Purpan, Toulouse, France
  7. 7 Cancer Research Center, INSERM UMR1037 CRCT, Toulouse, France
  8. 8 Biochemistry, Metabolomic and Proteomic Department, Necker Enfants Malades University Hospital, Assistance Publique Hôpitaux de Paris, UMRS 1151, INSERM, Institute Necker Enfants Malades, Paris Descartes University, Paris, France
  9. 9 UF Maladies Héréditaires Enzymatiques Rares—CGD, Institut de Biologie et de Pathologies, CHU de Grenoble Alpes, Grenoble, France
  10. 10 Department of Genetics, Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, F76000, Normandy Centre for Genomic and Personalized Medicine, ROUEN, France
  11. 11 Biochemical and Molecular Biology Department, Centre de Biologie et de Pathologie Est Hospices Civils de Lyon, Lyon, France
  12. 12 Department of Pediatric Gastroenterology, hepatology and Nutrition, University hospital of Montpellier, Montpellier, France
  13. 13 Department of Clinical Genetic, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
  14. 14 Metabolic Medicine Department, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street Institute of Child Health, University College London, London, UK
  15. 15 Department of Inherited Metabolic Disease, Necker-Enfants Malades University Hospital, AP-HP, Paris, France
  16. 16 Reference Center of Inherited Metabolic Diseases, Necker Enfants Malades Hospital, Imagine Institute, University Paris Descartes, Paris, France
  17. 17 Département de Génétique Médicale, Hôpital Timone Enfant, Marseille, France
  18. 18 Centre de Référence des Maladies Héréditaires du Métabolisme, Service de Neuropédiatrie, CHU La Timone Enfants, APHM, Marseille, France
  19. 19 Genetic Services, A. de Villeneuve Hospital, Montpellier, France
  20. 20 Department of Paediatric Neurology, Hopital universitaire Necker-Enfants malades Service de Pediatrie generale, Paris, Île-de-France, France
  21. 21 Service de génétique, CHRU Reims, Reims, France
  22. 22 EA3801, UFR médecine, France
  23. 23 Department of Hematolog, Hôpital Emile Muller - CH de Mulhouse, Mulhouse, France
  24. 24 Pediatric Genetics, Marmara University Medical School, Istanbul, Turkey
  25. 25 Genetics, Children's Hospital, Ain Shams University, Cairo, Egypt
  26. 26 Department of Pediatric Metabolism, Reference Center of Inherited Metabolic Disorders, Femme Mère Enfant Hospital, Lyon, France
  27. 27 Genetic department, CHU-Reims, EA3801, SFR CAP santé, Reims, France
  28. 28 Department of Neonatology and Paediatrics, Centre Hospitalier de la Côte Basque, Bayonne, France
  29. 29 Pediatric Critical Care Unit, Femme-Enfants-Adolescents Hospital, Nantes University, Nantes, France
  30. 30 Regional University Hospital Centre Tours, Tours, Centre, France
  31. 31 Reference Centre for Inborn Errors of Metabolism, Robert-Debré University Hospital, APHP, Paris, France
  32. 32 Department of Pediatrics, Bordeaux University Hospital, Bordeaux, France
  33. 33 CHU Lyon, Lyon, Auvergne-Rhône-Alpes, France
  34. 34 INSERM U 1051, Institut des Neurosciences de Montpellier, Montpellier, Hérault, France
  35. 35 Département de Neuropédiatrie, CHU Gui de Chauliac, Montpellier, France
  36. 36 Genetics, Hôpital d'Enfants de la Timone, Marseille, France
  37. 37 Department of Pediatrics, Reference Center of Inherited Metabolic Disorders, Clocheville Hospital, Tours, France
  38. 38 Department of Metabolic Biochemistry, University Hospital Centre Rouen, Rouen, Normandie, France
  1. Correspondence to Dr Soumeya Bekri, Department of Metabolic Biochemistry, University Hospital Centre Rouen, 76031 Rouen, Normandie, France; soumeya.bekri{at}


Introduction This study aims to define the phenotypic and molecular spectrum of the two clinical forms of β-galactosidase (β-GAL) deficiency, GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B, MPSIVB).

Methods Clinical and genetic data of 52 probands, 47 patients with GM1-gangliosidosis and 5 patients with MPSIVB were analysed.

Results The clinical presentations in patients with GM1-gangliosidosis are consistent with a phenotypic continuum ranging from a severe antenatal form with hydrops fetalis to an adult form with an extrapyramidal syndrome. Molecular studies evidenced 47 variants located throughout the sequence of the GLB1 gene, in all exons except 7, 11 and 12. Eighteen novel variants (15 substitutions and 3 deletions) were identified. Several variants were linked specifically to early-onset GM1-gangliosidosis, late-onset GM1-gangliosidosis or MPSIVB phenotypes. This integrative molecular and clinical stratification suggests a variant-driven patient assignment to a given clinical and severity group.

Conclusion This study reports one of the largest series of b-GAL deficiency with an integrative patient stratification combining molecular and clinical features. This work contributes to expand the community knowledge regarding the molecular and clinical landscapes of b-GAL deficiency for a better patient management.

  • brain damage
  • chronic
  • brain diseases
  • metabolic
  • central nervous system diseases
  • genomics

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • Contributors SB conceived and supervised the study. SB, PS-V, BS-A, SSn, HD and SC generated and analysed the molecular data. SB, TL, CCa, SV and RF performed enzymatic analyses. IDa, ST, LD, BH, MAK, YA, JB, AB, A-CB, TB, AC, BC, CC, ID, MD-F, BD, NHE, SM, AF, CP, AG, PJ, AK, FL, LL, SP, SaR, SRo, SR, AR, SS, MS, MT, CV and SM curated the clinical data. AT performed data integration, analysis and visualisation. SB and AT wrote the manuscript. All authors read and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.