Mucolipidosis III gamma (gamma Mucolipidosis III) - Gen GNPTG
The ML III gamma is a slowly progressive disease that affects many parts of the body. Signs and symptoms of this condition usually occur around 3 years and generally include slow growth, short stature, joint stiffness, dysostosis multiplex and osteoporosis. Frequently affected individuals also have abnormalities in cardiac and corneal opacity valves. His facial features become slightly thick or "rough" as they age. In addition, a small percentage of people with this disease have mild problems learning or intellectual disabilities. Individuals with ML III gamma generally survive to adulthood, but may have a shorter life.
Mucolipidosis III gamma is due to alterations in the gene sequence GNPTG (N-acetylglucosamine-1-phosphate transferase gamma subunit), located on the short arm of chromosome 16 (16p13.3). This gene encodes the gamma subunit of an enzyme called GlcNAc-1-phosphotransferase. This enzyme is composed of two alpha subunits, two beta and gamma two subunits. Beta and gamma subunits are encoded from a different gene, GNPTAB (N-acetylglucosamine-1-phosphate transferase alpha and beta subunits). GlcNAc-phosphotransferase 1 helps prepare certain enzymes for transport to the lysosomes enzyme. Lysosomes are compartments inside the cell using enzymes to degrade large molecules into smaller units that can be reused by cells. GlcNAc-phosphotransferase 1 is involved in the process of attaching a molecule mannose 6-phosphate (M6P) to specific enzymes. M6P acts as a label indicating a hydrolase must be transported to the lysosomes. Once a hydrolase has a M6P tag, you can be transported to a lysosome.
Found at least 8 mutations in the gene responsible for GNPTG mucolipidosis III gamma. These mutations result in the synthesis of a GlcNAc-phosphotransferase 1 with reduced activity, interrupting labeling hydrolases M6P. Instead, hydrolases end outside the cell with an increased extracellular activity. The absence of hydrolases in lysosomes causes large molecules accumulate there. Alterations that cause the molecules accumulate in the lysosomes, including gamma mucolipidosis III, are called lysosomal storage disorders. Signs and symptoms of gamma mucolipidosis III are probably due to the absence or deficiency of hydrolases in the lysosomes and the effects that these enzymes are outside the cell.
This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with mucolipidosis III gamma through the complete PCR amplification of exons GNPTG gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).