Mucolipidosis type III gamma: Three novel mutation and genotype-phenotype study in eleven patients

Mucolipidosis type III gamma (MLIII gamma) is a lysosomal storage disease characterized by joint stiffness, mild coarse face and corneal clouding, which becomes recognizable usually in childhood. Biallelic mutations in the GNPTG gene, which encode the γ subunit of the N-acetylglucosamine-1-phosphotransferase enzyme, are the underlying cause of MLIII gamma. The aim of this study is to evaluate the longitudinal findings and genotype of eleven patients from eight families with MLIII gamma and to establish a genotype-phenotype correlation. The most frequently observed initial finding was stiffness of finger joints, which detected in patients between 18month-olds and five year-olds. However, in four patients presented here, initial finding was knee pain or waddling gait, which started between six-16years of age. All patients also had variable degrees of stiffness on large joints. The longest follow up period was 16years while the shortest was three years and six months. We observed that the patients who had an early onset disease and severe joint stiffness had also rapidly progressive joint involvement mostly localized in hands, shoulders, and hip. However; the patients with late onset and/or mild joint stiffness experienced slowly progressive symptoms. Most patients dropped in their growth curve in time and the ones who were severely affected reached the final height below the third centile. Seven disease-causing mutations, three of them novel, were detected in GNPTG gene. According to our clinical observations c.493_494insC and c.283_284insC mutations lead to a severe phenotype and c.196C>T, c.347_349del, c.652_655delTACT and c.445delG/c.367A>G mutations seemed to generate a milder phenotype. •Here, we report longitudinal clinical findings and genotype-phenotype correlation of eleven patients from eight unrelated families with MLIII gamma. This detailed longitudinal observation enabled us to give information regarding both the onset of disease associated symptoms and new disease symptoms appear so that the readers could obtain valuable information about the progress of the disease.•We described three novel disease-causing mutations in GNPTG gene.•We observed that the presence of c.493_494insC and c.283_284insC insertion mutations in GNPTG gene was associated with severe clinical phenotype with an earlier onset of signs and symptoms. The prognosis of these patients was poorer than the others. However c.196C>T, c.347_349del, c.652_655delTACT, and c.367A>G/c.445