Icon for French language translation. Galactosialidosis

What is Galactosialidosis?

Galactosialidosis is one of seven identified Glycoprotein storage diseases.

These inherited diseases are part of a larger group of disorders called Lysosomal storage diseases. Lysosomes are membrane-bound compartments found in the cells of the body. These compartments contain enzymes, which are responsible for the breakdown of many different oligosaccharides (long sugar chains.) These sugar chains are continuously made and broken down in our bodies, and this process is necessary for appropriate mental and physical development. Each enzyme in the lysosome is responsible for a certain step in the breakdown of the sugar chains.

When an enzyme is not working, it leads to the build up of the sugar chains in the lysosome. In Galactosialidosis, the specific enzyme that is absent is called Protective Protein/Cathepsin A (PPCA). This enzyme works with two other enzymes, B-Galactosidase and Neuraminidase, to break down oligosaccharides. PPCA also helps in protecting the enzymes Galactosidase and Neuraminidase from being broken down in the lysosome. Thus, when PPCA is absent, it also leads to the absence of B-Galactosidase and Neuraminidase.

The build up of oligosaccharide sugars that is caused, is gradual and interferes with the correct function of the cell. This build up is gradual and eventually leads to the clinical features of Galactosialidosis. Features may present in severity over time.

In Galactosialidosis, the specific enzyme that is absent is called Protective Protein/Cathepsin A (PPCA). This enzyme works with two other enzymes, B- Galactosidase and Neuraminidase, to break down oligosaccharides. PPCA also helps in protecting the enzymes Galactosidase and Neuraminidase from being broken down in the lysosome. Thus, when PPCA is absent, it also leads to the absence of B-Galactosidase and Neuraminidase.

What are the clinical features of Galactosialidosis?

Individuals with Galactosialidosis show the typical physical characteristics shared by many of the lysosomal storage diseases. These include coarse facial features, dysostosis multiplex (abnormal bone formation found in multiple bones of the body) seen on x-ray, and cherry red spots seen on ophthalmology evaluation. Cherry red spots are small areas on the retina where sugar chain storage has occurred making the remainder of the healthy surrounding retina appear a brighter red.

There are three different types of Galactosialidosis. They are characterized by the age of onset and type of physical and mental manifestations. Type I is called the early infantile type of Galactosialidosis, and onset is typically between birth and three months of age. Individuals with this type of Galactosialidosis present with hydrops, edema, and ascites (fluid accumulation in different parts of the body.) Occasionally, hepatosplenomegaly (large liver and/or spleen) is present. Infants with Galactosialidosis may have skeletal changes, especially involving the spine. Cognitive and motor delay is also present. The presence of telangectasias (dilation of blood vessels, most commonly on the skin) is unique to the early infantile type of Galactosialidosis. Ophthalmology evaluation may show cherry red spots or other eye changes including corneal clouding. Echocardiogram may show cardiomegaly (enlarged heart), specifically with a thickening of the septum (wall of the heart that separates the right and left sides of the heart.) Kidney function can be impaired, and there may be increased protein detected in the urine. Cardiac and/or renal failure is typically the cause of death in individuals with early infantile Galactosialidosis.

Average age of death is usually under one year of life. The second type of Galactosialidosis is called the late infantile type and onset is within the first few months of life. Individuals usually present with coarse facial features, hepatosplenomegaly, and dysostosis multiplex. Bony changes are especially noticeable in the spine. Cherry red spots and/or corneal clouding may be present. Neurological problems such as ataxia (inability to coordinate voluntary muscular movements) or seizures are rarely seen in the late infantile type of Galactosialidosis. Mental retardation may be present and is generally mild. Cardiac findings usually involve thickened valves within the heart. Additionally, hearing loss may occur.

The majority of individuals with Galactosialidosis have the third type, the juvenile/adult type of Galactosialidosis. The juvenile/adult type has a wide range of severity of features and age of onset. The average age that symptoms appear is around 16 years, but may present initially as late as the 3rd or 4th decade. Additionally, individuals with this type of Galactosialidosis are predominantly of Japanese origin. Common findings include coarse facial features (although less severe than in other lysosomal storage diseases) and spinal changes. Dysostosis multiplex is usually not seen. Neurological problems such as ataxia, seizures, and deteriorating mental abilities may also be present. Typical eye abnormalities include cherry red spots, corneal clouding, and vision loss. Hepatosplenomegaly is usually not present. Angiokeratomas (superficial blood vessel dilations over which wartlike growths occur) are typical for the juvenile/adult form but are not present in the early or late infantile forms of Galactosialidosis.

How is Galactosialidosis inherited?

Galactosialidosis is not contagious and cannot be “caught.” It is a genetic condition, which means that it is caused by a change in the instructions that direct the way our bodies grow and develop. These instructions are called genes. People have two copies of all their genes, including the gene for Galactosialidosis (PPCA). One copy is inherited from the mother in the egg, and one from the father in the sperm.

Only when there is a change in the gene code is there a possibility that the disease will occur. For a person to have Galactosialidosis, they must inherit changes in both of their PPCA genes resulting in instructions that do not function properly. This is known as autosomal recessive inheritance.

For a couple to have a child with Galactosialidosis, both parents must have at least one changed copy of the PPCA gene, which they both pass on to their child. Parents do not have control over which genes they pass on to their children.

If a person has one changed copy of the PPCA gene and one normal copy of the PPCA gene, they are said to be a “carrier” of the condition and will not show any symptoms of Galactosialidosis. If two parents are both carriers, they have a 1 in 4 (25%) chance of having a child with Galactosialidosis in each pregnancy.

What testing is available to determine if my child or I have Galactosialidosis?

Testing for Glycoprotein storage diseases is typically performed in conjunction with a genetics evaluation. A genetics team takes into account the medical history and clinical features of a patient to determine what type of genetic testing is appropriate. For the diagnosis of an Glycoprotein storage disease, a urine test should show increased oligosaccharides. To determine if the patient has Galactosialidosis, the urine test should be followed by a blood test or skin biopsy. The blood or skin sample should show decreased amounts of the enzymes B- Galactosidase and Neuraminidase.

For families who have had a child diagnosed with Galactosialidosis, prenatal diagnosis is available in future pregnancies by looking at B-Galactosidase and Neuraminidase activity through Chorionic Villus Sampling (CVS) or amniocentesis. Prenatal diagnosis by detection of PPCA gene changes is also available for families in which the responsible gene changes have been identified.

What type of treatment is available for Galactosialidosis?

Individuals with Galactosialidosis should have routine follow-up with Genetics, Ophthalmology, Cardiology, and other specialists as needed. Currently there is no cure to stop the progression of symptoms of Galactosialidosis, and treatment is aimed at addressing the individual problems as they arise.

For some Glycoprotein diseases, bone marrow transplant has been trialed as an experimental therapy but there are no conclusive results on the long term benefits. Ask your specialist for more information on this.

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