Mucolipidosis type II and type III: a systematic review of 843 published cases

Emma J. Dogterom, Margreet A.E.M. Wagenmakers, Martina Wilke, Serwet Demirdas, Nicole M. Muschol, Sandra Pohl, Jan C.van der Meijden, Dimitris Rizopoulos, Ans T.van der Ploeg, Esmée Oussoren*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

17 Citations (Scopus)


Purpose: Mucolipidosis (ML) II, MLIII alpha/beta, and MLIII gamma are rare autosomal recessive lysosomal storage disorders. Data on the natural course of the diseases are scarce. These data are important for counseling, therapies development, and improvement of outcome. The aim of this study is to gain knowledge on the natural history of ML by obtaining data on survival, symptom onset, presenting symptoms, diagnosis, and pathogenic variants associated with the MLII or MLIII phenotype. Methods: A systematic review on all published MLII and MLIII cases between 1968 and August 2019 was performed. Results: Three hundred one articles provided data on 843 patients. Median age at diagnosis: 0.7 for MLII and 9.0 years for MLIII. Median survival: 5.0 for MLII and 62.0 years for MLIIIII. Median age of death: 1.8 for MLII and 33.0 years for MLIII. Most frequent causes of death in all ML were pulmonary and/or cardiac complications. Pathogenic variants were described in 388 patients (GNPTAB: 571, GNPTG 179). Conclusion: This review provides unique insights into the natural history of MLII and MLIII, with a clear genotype–phenotype correlation with the most frequent pathogenic variant c.3503_3504del in MLII and in MLIII alpha/beta c.22A>G for GNPTAB. All pathogenic GNPTG variants resulted in MLIII gamma.

Original languageEnglish
Pages (from-to)2047-2056
Number of pages10
JournalGenetics in Medicine
Issue number11
Early online date25 Jun 2021
Publication statusPublished - Nov 2021

Bibliographical note

Funding Information:
M.A.E.M.W. received an unrestricted research grant from the Nutricia metabolics research fund. A.T.v.d.P. gives advice to several pharmaceutical companies about the implementation and development of innovative therapies, mainly for Pompe disease, but also for other LSDs and neuromuscular disorders. Furthermore, she received funds for research via agreements between Erasmus MC and pharmaceutical companies. She also advices public or private charities, who aim to improve the care for patients with metabolic diseases. The other authors declare no competing interests.

Funding Information:
The authors thank Wichor M. Bramer from the Erasmus MC Medical Library for developing and updating the search strategies. This study is part of an ongoing collaboration within the lysosomal subnetwork of the European Reference Network for Hereditary Metabolic Disorders (MetabERN). This work was supported by the Smile for I Cell Foundation (, Janivo Foundation, and Stofwisselkracht.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.

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  • EMC MM-01-54-01


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