Mucolipidosis II alpha / beta (Mucolipidosis II alpha / beta) - Gen GNPTAB

Mucolipidosis II alpha / beta, also known as I - cell disease, is a progressive debilitating disease that affects many parts of the body. At birth, children affected are small and have hypotonia and weak cry. After birth, these individuals grow slowly and usually stop growing during the second year of life. Delayed development, particularly the development of motor skills and speech. In addition, children with mucolipidoses II alpha / beta typically have multiple bone abnormalities such as multiple dysostosis, kyphosis, clubfoot, hip dislocation, unusually long bones and short hands and digits. In addition, these individuals have joint deformities that significantly affect mobility. Most children with mucolipidoses II alpha / beta do not develop the ability to walk independently.

Other features of the mucolipidosis II alpha / beta include umbilical hernia or inguinal hernia, abnormal heart valves, facial features distinctive appearance described as "rough", and gingival hypertrophy. The vocal cords may harden, causing a hoarse voice. The airway is narrow, which may contribute to frequent and prolonged respiratory infections. Affected individuals may also have frequent ear infections that can lead to hearing loss. Individuals most affected do not survive beyond infancy.

This process is due to mutations in the gene GNPTAB (N-acetylglucosamine-1-phosphate transferase alpha and beta subunits), located on the long arm of chromosome 12 (12q23.2). This gene encodes the alpha and beta subunits of GlcNAc-phosphotransferase enzyme 1. This enzyme is composed of two alpha subunits, two beta and gamma two subunits. The gamma subunit is encoded from a different gene, called GNPTG (N-acetylglucosamine-1-phosphate transferase gamma subunit). GlcNAc-phosphotransferase 1 helps prepare certain enzymes for transport to the lysosomes enzyme. Lysosomes are compartments inside the cell using digestive 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 called mannose 6-phosphate (M6P) to specific digestive 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.

They have been described at least 132 mutations in the gene GNPTAB corresponding to :: missense mutations (54), and cutting mutations -splicing- connection (14), small deletions (33), small insertions (26), small indels (2) major deletions (1) and larger insertions and duplications (2). These mutations inhibit any encoding GlcNAc-1-phosphotransferase functional. Without this enzyme, hydrolases not be labeled with M6P and transported to lysosomes. Instead, hydrolases end outside the cell with an increased cell digestive activity. The absence of hydrolases in lysosomes causes large molecules accumulate there. Alterations that cause the molecules accumulate in the lysosomes, including mucolipidosis II alpha / beta, are called lysosomal storage disorders. Signs and symptoms of mucolipidosis II alpha / beta are probably due to the absence or deficiency of hydrolases in the lysosomes and the effects that these enzymes are outside the cell.

Mutations in the gene GNPTAB may also lead to a similar but milder, called mucolipidosis III alpha / beta. In this process, instead of inhibiting the synthesis of any enzyme, these mutations reduce the activity of GlcNAc-1-phosphotransferase.

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 II alpha / beta, by complete PCR amplification of exons GNPTAB 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).