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Genetic and Rare Diseases Information Center (GARD)

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Galactosialidosis


Other Names for this Disease
  • Cathepsin A deficiency of
  • Goldberg syndrome
  • GSL
  • Lysosomal protective protein deficiency of
  • Neuraminidase deficiency with beta-galactosidase deficiency
More Names
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Overview



What is galactosialidosis?

What are the signs and symptoms of galactosialidosis?

What causes galactosialidosis?

How is galactosialidosis inherited?


What is galactosialidosis?

Galactosialidosis is an autosomal recessive lysosomal storage disorder caused by mutations in the CTSA gene.[1][2] It is characterized by coarse facial features, macular cherry-red spots, angiokeratoma (dark red spots on the skin), vertebral deformities, epilepsy, action myoclonus, and ataxia.[3] There are three different types of galactosialidosis: early infantile, late infantile and juvenile/adult. The three forms of galactosialidosis are distinguished by the age at which symptoms develop and the pattern of features.[1][4]
Last updated: 5/16/2011

What are the signs and symptoms of galactosialidosis?

The early infantile form of galactosialidosis is associated with hydrops fetalis, inguinal hernia, and hepatosplenomegaly. Additional features include abnormal bone development (dysostosis multiplex) and distinctive facial features that are often described as 'coarse.' Some infants have an enlarged heart; an eye abnormality called a cherry-red spot (identified through an eye examination); and kidney disease that can progress to kidney failure. Infants with this form are usually diagnosed between birth and 3 months of age.[1]

The late infantile form of galactosialidosis shares some features with the early infantile form, although the signs and symptoms are somewhat less severe and begin later in infancy. This form is characterized by short stature, dysostosis multiplex, heart valve problems, hepatosplenomegaly, and 'coarse' facial features. Other symptoms seen in some individuals with this type include intellectual disability, hearing loss, and a cherry-red spot. Children with this condition typically develop symptoms within the first year of life.[1]

The juvenile/adult form of galactosialidosis has signs and symptoms that are somewhat different than those of the other two types. This form is distinguished by difficulty coordinating movements (ataxia), muscle twitches (myoclonus), seizures, and progressive intellectual disability. People with this form typically also have dark red spots on the skin (angiokeratomas), abnormalities in the bones of the spine, 'coarse' facial features, a cherry-red spot, vision loss, and hearing loss. The age at which symptoms begin to develop varies widely among affected individuals, but the average age is 16.[1]

Last updated: 5/16/2011

What causes galactosialidosis?

Galactosialidosis is caused by mutations in the CTSA gene. The CTSA gene provides instructions for making a protein called cathepsin A, which is active in cellular compartments called lysosomes. These compartments contain enzymes that digest and recycle materials when they are no longer needed. Cathepsin A works together with two enzymes, neuraminidase 1 and beta-galactosidase, to form a protein complex. This complex breaks down sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins) or fats (glycolipids). Cathepsin A is also found on the cell surface, where it forms a complex with neuraminidase 1 and a protein called elastin binding protein. Elastin binding protein plays a role in the formation of elastic fibers, a component of the connective tissues that form the body's supportive framework.[1]

CTSA mutations interfere with the normal function of cathepsin A. Most mutations disrupt the protein structure of cathepsin A, impairing its ability to form complexes with neuraminidase 1, beta-galactosidase, and elastin binding protein. As a result, these other enzymes are not functional, or they break down prematurely.[1]

Galactosialidosis belongs to a large family of lysosomal storage disorders, each caused by the deficiency of a specific lysosomal enzyme or protein. In galactosialidosis, impaired functioning of cathepsin A and other enzymes causes certain substances to accumulate in the lysosomes.[1]

Last updated: 5/16/2011

How is galactosialidosis inherited?

Galactosialidosis is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.[1]
Last updated: 5/16/2011

References
  1. Galactosialidosis. Genetics Home Reference (GHR). 2009; http://ghr.nlm.nih.gov/condition/galactosialidosis. Accessed 5/16/2011.
  2. Maire I, Froissart R. Galactosialidosis. Orphanet. 2005; http://www.orphanet.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=351. Accessed 5/16/2011.
  3. Kruer MC. Lysosomal Storage Disease. eMedicine. 2008; http://emedicine.medscape.com/article/1182830-overview#showall. Accessed 5/16/2011.
  4. Galactosialidosis. Hide & Seek Foundation for Lysosomal Disease Research. http://www.hideandseek.org/index.php?option=com_content&task=view&id=121&Itemid=75. Accessed 5/16/2011.