The Piranha

Mucolipidosis Type II and Type III

Mucolipidosis type II (ML II) and mucolipidosis type III (ML III) are caused by a defect of the GlcNAc-1-phosphotransferase complex, which is composed of three subunits, alpha, beta und gamma. Mutations of the gene GNPTAB encoding the alpha/beta subunits result in Mucolipidosis II (ML II, also called I-cell disease) or the clinically milder condition mucolipidosis (ML III) alpha/beta. ML III gamma (or ML IIIC) arises from mutations of the gene GNPTG encoding the gamma-subunit. The GlcNAc-1-phosphotransferase complex is responsible for the formation of the mannose-6-phosphate recognition marker required for correct targeting of lysosomal hydrolases to the lysosomes. A defect of this complex leads to missorting of multiple lysosomal enzymes ending in the accumulation of different non-degraded macromolecultes in several tissues and organs. In ML II (I-cell disease) clinical signs are present already in newborns, these include dysmorphic features with striking gingival hypertrophy, developmental disturbance, skeletal abnormalities, hepatosplenomgaly and cardiomyopathy; the patients often die in early childhood. The  mucolipidosis III (ML III alpha/beta and ML III gamma) are slowly progressive disorders that mainly affect the skeletal, joint and connective tissue, but spare the central nervous system. The life expectany is hardly reduced.