Mucolipidosis II and III alpha/beta
Mucolipidosis II and III alpha/beta belong to a group of rare genetic disorders that affect the production or function of lysosomal enzymes. When these enzymes do not function correctly, cells cannot break down certain substances, such as carbohydrates and lipids, leading to accumulations that induce cellular and tissue damage in multiple organs.
Mucolipidosis II and III are caused by mutations in the GNPTAB gene, which encodes the alpha (α) and beta (β) subunits of the enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase). The severity of these disorders depends on the type of GNPTAB mutation: mutations that eliminate all enzyme function cause mucolipidosis type II, while mutations that only reduce function cause mucolipidosis type III.
Their prevalence is estimated to be approximately 1 case per 1,000,000 people, although it may be higher in certain geographic areas such as the Saguenay-Lac-Saint-Jean region of Quebec.
Symptoms
Mucolipidosis II is the most severe form, with symptoms evident at birth or in early childhood. These include characteristic facial features, skeletal anomalies, slow growth, joint stiffness, and psychomotor developmental delay. Mucolipidosis III is milder and slower progressing, with onset in early childhood. The main symptoms are progressive joint stiffness, short stature, hip dysplasia, and cardiac involvement.
Disease management
Currently there is no cure and treatment focuses on improving the patient's quality of life, requiring a multidisciplinary team. There are programs that stimulate cognitive development and they are also monitored to control respiratory and cardiac functions.
Genes analyzed
Bibliography
Khan SA, Tomatsu SC. Mucolipidoses Overview: Past, Present, and Future. Int J Mol Sci. 2020 Sep 17;21(18):6812.
Paik KH, Song SM, Ki CS, et al. Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II or type IIIA. Hum Mutat. 2005 Oct;26(4):308-14.
Velho RV, De Pace R, Klünder S, et al. Analyses of disease-related GNPTAB mutations define a novel GlcNAc-1-phosphotransferase interaction domain and an alternative site-1 protease cleavage site. Hum Mol Genet. 2015 Jun 15;24(12):3497-505.
