Mucolipidosis type III, a series of adult patients

Robin Lachmann,Rob Verdijk,George J G Ruijter,Mirjam Langeveld,Elaine Murphy,Esmee Oussoren,Jan C Van Der Meijden,Janneke G Langendonk,Carla E M Hollak,Mario Maas,Ans T Van Der Ploeg,Lies H Hoefsloot,David Van Eerd

doi:10.1007/s10545-018-0186-z

Abstract

BackgroundMucolipidosis type III α/β or γ (MLIII) are rare autosomal recessive diseases, in which reduced activity of the enzyme UDP-N-acetyl glucosamine-1-phosphotransferase (GlcNAc-PTase) leads to intra-lysosomal accumulation of different substrates. Publications on the natural history of MLIII, especially the milder forms, are scarce. This study provides a detailed description of the disease characteristics and its natural course in adult patients with MLIII.MethodsIn this retrospective chart study, the clinical, biochemical and molecular findings in adult patients with a confirmed diagnosis of MLIII from three treatment centres were collected.ResultsThirteen patients with MLIII were included in this study. Four patients (31%) were initially misdiagnosed with a type of mucopolysaccharidosis (MPS). Four patients (31%) had mild cognitive impairment. Six patients (46%) needed help with activities of daily living (ADL) or were wheelchair-dependent. All patients had dysostosis multiplex and progressive secondary osteoarthritis, characterised by cartilage destruction and bone lesions in multiple joints. All patients underwent multiple orthopaedic surgical interventions as early as the second or third decades of life, of which total hip replacement (THR) was the most common procedure (61% of patients). Carpal tunnel syndrome (CTS) was found in 12 patients (92%) and in eight patients (61%), CTS release was performed.ConclusionsSevere skeletal abnormalities, resulting from abnormal bone development and severe progressive osteoarthritis, are the hallmark of MLIII, necessitating surgical orthopaedic interventions early in life. Future therapies for this disease should focus on improving cartilage and bone quality, preventing skeletal complications and improving mobility.

Highlights

Mucolipidoses type II/III α/β or γ (MLII OMIM#252500, Mucolipidosis type III α/β or γ (MLIII) α/β MIM#252600, MLIII γ OMIM#252605) are rare autosomal recessive diseases (Maroteaux and Lamy 1966; Leroy and Martin 1975; Raas-Rothschild et al 2000, 2004; Cathey et al 2008, 2010)
GlcNAc-PTase is responsible for the first step in the phosphorylation of enzyme-conjugated mannose residues to mannose-6phosphate in the Golgi apparatus
The aim of this study is to provide a detailed description of the disease characteristics of MLIII and its natural course, by studying data from adult patients

Summary

Introduction

Mucolipidoses type II/III α/β or γ (MLII OMIM#252500, MLIII α/β MIM#252600, MLIII γ OMIM#252605) are rare autosomal recessive diseases (Maroteaux and Lamy 1966; Leroy and Martin 1975; Raas-Rothschild et al 2000, 2004; Cathey et al 2008, 2010) In these conditions, activity of the membrane-bound hexameric enzyme UDP-N-acetyl glucosamine-1-phosphotransferase (GlcNAc-PTase), consisting of three subunits named α2, β2 and γ2, is absent or reduced (Reitman and Kornfeld 1981; Bao et al 1996; Raas-Rothschild et al 2000; Kudo et al 2005; Tiede et al 2005). III α/β or γ (MLIII) are rare autosomal recessive diseases, in which reduced activity of the enzyme UDP-N-acetyl glucosamine-1-phosphotransferase (GlcNAc-PTase) leads to intra-lysosomal accumulation of different substrates.

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