Mucopolysaccharidosis IX (Mucopolysaccharidosis type IX) - Gen HYAL1.

Mucopolysaccharidoses encompasses a group of inherited metabolic diseases caused by the absence or malfunction of certain necessary for processing glycosaminoglycans, found in bone, cartilage, tendons, corneas, skin and connective tissue enzymes. The glycosaminoglycans (formerly called mucopolysaccharides) are also present in the synovial fluid of the joints. People suffering from mucopolysaccharidosis not encode sufficient quantities of one of the eleven enzymes required to transform glycosaminoglycans in protein and simpler molecules, or encode enzymes that do not work properly. Over time, these glycosaminoglycans accumulate in cells, blood and connective tissues. This produces permanent and progressive cellular damage that affect the appearance and physical abilities, organs and body functions of the individual and, in most cases, mental development.

Mucopolysaccharidosis IX (MPS9) is a lysosomal storage disease characterized by a high concentration of hyaluronic serum. Clinical features include periarticular soft tissue masses, short and mild acetabular erosions. Affected individuals show no neurological or visceral involvement. Symptoms such as formation of nodular masses around the joints, episodes of painful swelling of the same and pains, cease within 3 days. In these individuals, joint effusions occur with some frequency. This process is due to mutations in the HYAL1 gene, located on the short arm of chromosome 3 (3p21.31). This gene, a tumor suppressor considered, encoding a lysosomal hyaluronidase. Intracellular hyaluronidases degrade hyaluronic, one of the principal glycosaminoglycans of the extracellular matrix. It is believed that the hyaluronic is involved in the proliferation, migration and differentiation. This enzyme is active at acidic pH and is the major hyaluronidase in the plasma.

Mutations in the HYAL1 gene associated with mucopolysaccharidosis IX, resulting in deficiency of hyaluronidase 1. The lack of activity of hyaluronidase 1 leads to the accumulation of GAGs within lysosomes. Due to the accumulation of molecules within lysosomes, this disease is considered an alteration of lysosomal storage. Accumulation of GAG increases the size of the cells, so many tissues and organs are enlarged. In addition, glycosaminoglycans are likely to interfere with the functions of other proteins within the lysosome.

This disease is inherited in an autosomal recessive pattern, that is, 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 mucopolysaccharidosis IX, by complete PCR amplification of exons HYAL1 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).