Galactosialidosis (Galactosialidosis) - Gen CTSA.

Galactosialidosis is a disorder that affects many areas of the body. There are three ways galactosialidosis which differ by age at which symptoms and pattern features are developed: early childhood form, late infantile form and juvenile / adult form.

Early infantile form is associated with fetal hydrops, inguinal hernia and hepatosplenomegaly, dysostosis multiplex and distinctive facial features. Some newborns have cardiomegaly, an eyespot cherry red and kidney disease can progress to kidney failure. Typically, newborns are diagnosed with this type between birth and 3 months old and usually live in later childhood.

The second type of galactosialidosis, late infantile form, shares some characteristics with early childhood form even though the signs and symptoms are somewhat less intense and start later in childhood. This form is characterized by short stature, dysostosis multiplex, problems in the heart valves, hepatosplenomegaly and "thick" facial features. Other symptoms seen in some individuals with this type include mental retardation, hearing loss and eye cherry - red stain. Children usually develop symptoms in the first year of life. The life expectancy of individuals with this type varies depending on the severity of symptoms.

The third type, the juvenile form / adult of galactosialidosis, have signs and symptoms that are somewhat different from the other two types. This form is characterized by ataxia, myoclonus, seizures and progressive mental retardation. In addition, people with this form usually have Angiokeratomas, bone abnormalities of the spine, "coarse" facial features, an eyespot cherry red, vision loss and hearing loss. The age at which symptoms begin to manifest themselves varies widely among individuals affected, but the average age is 16 years. Generally, this form has a normal life expectancy.

Galactosialidosis is due to mutations in the CTSA gene, located on the long arm of chromosome 20 (20q13.1). This gene encodes cathepsin protein A. This protein acts as a protease and as a protective protein, interacting with other enzymes to prevent premature decomposition. Based on this protection, this enzyme is also called protective / cathepsin A or PPCA protein. Cathepsin A is active in lysosomes, and interacts with ?-galactosidase and neuraminidase 1 enzymes, which play a role in the breakdown of complex oligosaccharides attached to glycoproteins or glycolipids. Cathepsin A forms a complex with these two enzymes and directs transport inside the cell lysosomes. In the lysosomes, cathepsin A activates enzymes and avoid decomposition. On the cell surface, cathepsin A complexed with neuraminidase 1 and elastin binding protein, forming the protein receptor binding elastin. This receptor complex plays a role in the formation of elastic fibers, which form the support frame body.

They have identified at least 20 mutations in the CTSA gene in people with galactosialidosis. Most of these mutations change the amino acid cathepsin A. In the Japanese population, the most common mutation (SpDEx7) alters the protein coding. Many mutations CTSA disrupt protein structure of cathepsin A, reducing its ability to bind neuraminidase 1 and beta-galactosidase or elastin binding protein. As a result, these other enzymes are nonfunctional or decompose prematurely. Most mutations in the gene result CTSA absence of functional cathepsin A and a loss of neuraminidase 1, beta-galactosidase, and elastin binding protein. It is not well understood how these four protein deficiency leads to the signs and symptoms of galactosialidosis.

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 galactosialidosis, by complete PCR amplification of exons CTSA 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).