On this page
Galactosialidosis
This condition results from a deficiency in specific lysosomal enzymes due to changes in the CTSA gene, leading to excessive storage of waste products within cells. It can affect various body systems, causing a range of symptoms from mild to severe.
Available at Jeen Health
Clinical tests that include this
Overview
Galactosialidosis is a very rare inherited metabolic disorder that impacts how the body processes certain complex molecules, specifically known as glycoproteins and glycolipids. It belongs to a group of conditions called lysosomal storage disorders. Lysosomes are like the recycling centres within cells, containing enzymes that break down waste products. In galactosialidosis, a specific enzyme deficiency means these waste products build up over time, interfering with normal cell and organ function [PMID:33678083].
The condition can manifest with varying severity, and doctors often classify it into early infantile, late infantile, and juvenile/adult forms, depending on when symptoms first appear and how quickly they progress [PMID:28755606]. While all forms arise from the same underlying genetic cause, the range of clinical features can be broad. As a rare condition, the exact number of people affected in the UK is not well established.
Symptoms & clinical features
The symptoms of galactosialidosis can differ significantly between individuals, even within the same family. In the early infantile form, which is typically the most severe, symptoms may appear shortly after birth and can include a swollen abdomen (hepatosplenomegaly), skeletal abnormalities, facial differences, and developmental delays [PMID:33678083]. Infants might also experience fluid buildup, known as hydrops fetalis, before birth.
In the late infantile and juvenile/adult forms, symptoms usually emerge later in childhood or adulthood and can progress more slowly. These might include difficulty with coordination (ataxia), vision problems (such as red spots in the eye or corneal clouding), hearing loss, seizures, and intellectual disability. Some individuals may also develop skin lesions, called angiokeratomas, and bone abnormalities. The specific constellation of symptoms depends on which cells and tissues are most affected by the accumulation of waste products.
Video: Genetics 101
Affected organs
Galactosialidosis can affect a wide range of organs and body systems due to the widespread nature of lysosomal storage. Commonly affected organs include the liver and spleen, which can become enlarged. The skeletal system is often involved, leading to abnormalities in bone structure. The central nervous system can also be significantly impacted, resulting in neurological symptoms such as developmental delay, intellectual disability, seizures, and problems with movement and balance [PMID:28755606].
Additionally, the eyes may show corneal clouding or 'cherry-red spots', and hearing can be impaired. The heart can sometimes be affected, leading to heart problems. In severe cases, multiple organ systems can progressively fail, leading to significant health challenges.
Risks & severity
The severity of galactosialidosis varies considerably, and it is usually categorised into early infantile, late infantile, and juvenile/adult types based on the age of symptom onset and disease progression. The early infantile form typically presents within the first few months of life and is often the most severe, with rapid progression and a shorter life expectancy. The late infantile form usually appears between 6 and 12 months and has a more variable course, but can still lead to significant health issues.
The juvenile/adult form is generally the mildest, with symptoms appearing later in childhood or adulthood, and can progress slowly over many years with a longer life expectancy. Lifetime risks depend heavily on the specific form of the condition an individual has. Prognosis is highly variable and depends on the specific mutations in the CTSA gene and the individual's clinical presentation.
Genetic causes
Galactosialidosis is caused by pathogenic changes (also known as mutations) in the CTSA gene. This gene provides instructions for making an enzyme called cathepsin A, also known as protective protein/cathepsin A (PPCA). This protein plays two crucial roles within the lysosomes of our cells.
Firstly, it acts as a protease, helping to break down certain proteins. Secondly, and very importantly in the context of galactosialidosis, it protects two other vital lysosomal enzymes - beta-galactosidase and neuraminidase - from being degraded themselves. Without functional CTSA, these other enzymes become unstable and are broken down prematurely. This leads to a deficiency of beta-galactosidase and neuraminidase, which are critical for breaking down specific complex sugars and proteins. Their absence causes these substances to accumulate within lysosomes, leading to the cellular dysfunction seen in galactosialidosis [PMID:28755606].
- CTSA cathepsin AThe CTSA gene provides instructions for producing cathepsin A, a lysosomal enzyme essential for the breakdown and recycling of various cellular components.
Inheritance pattern
Galactosialidosis is inherited in an autosomal recessive pattern. This means that an individual must inherit two altered copies of the CTSA gene - one from each parent - to develop the condition. People who have only one altered copy of the CTSA gene are called carriers. Carriers typically do not show symptoms of galactosialidosis because their single working copy of the gene is sufficient to produce enough functional cathepsin A.
When two carriers have children, there is a 25% chance with each pregnancy that their child will inherit two altered copies of the gene and therefore be affected by galactosialidosis. There is a 50% chance the child will be a carrier like their parents, and a 25% chance the child will inherit two working copies of the gene and not be a carrier or affected.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosing galactosialidosis typically begins with a thorough clinical assessment based on the individual's symptoms. This may include a physical examination, imaging studies, and developmental assessments. Clinical suspicion can be supported by laboratory tests that measure the activity of specific enzymes in blood or skin cells. These tests can reveal the deficient activity of beta-galactosidase and neuraminidase, which are indirectly caused by the CTSA gene changes.
The definitive diagnosis is confirmed through genetic testing, which involves analysing the CTSA gene for pathogenic changes. In the UK, genetic testing for suspected lysosomal storage disorders like galactosialidosis is typically initiated through a referral to a clinical genetics service or a metabolic specialist within the NHS. This testing falls under the NHS Genomic Medicine Service (GMS) and may be covered by relevant R-codes, ensuring a standardised diagnostic pathway. Genetic counsellors play a key role in explaining the testing process, results, and implications for the individual and their family.
Management & lifestyle
Currently, there is no cure for galactosialidosis, and management focuses on supportive care to address the specific symptoms an individual experiences. This often involves a multidisciplinary team of specialists including neurologists, ophthalmologists, audiologists, cardiologists, and developmental paediatricians, tailoring care to individual needs. For some lysosomal storage disorders, enzyme replacement therapy or bone marrow transplantation are options, but these are not currently established treatments for galactosialidosis itself.
Regular monitoring of affected organ systems is important to manage complications as they arise. For example, anti-epileptic medications may be used to control seizures, and therapies to improve mobility or communication skills may be recommended. Management within the NHS includes access to specialist genetic and metabolic clinics, where ongoing care and advice are provided. Genetic counselling is also a crucial part of the management pathway, offering support and information to families regarding inheritance and future planning.
UK care pathway
For individuals in the UK suspected of having conditions like galactosialidosis, the care pathway typically begins with a referral to a clinical genetics service or a metabolic specialist within the NHS. Genetic testing is a key component of diagnosis within the NHS Genomic Medicine Service (GMS). This testing follows a structured approach, often guided by specific R-codes which define the genetic tests available for various conditions. Access to genetic counsellors is integral to this pathway, providing essential support and information to patients and their families, helping them understand complex genetic results and their implications.
Frequently asked questions
What is autosomal recessive inheritance?
Autosomal recessive inheritance means a person must inherit two altered copies of a specific gene - one from each parent - to be affected by the condition. Individuals with only one altered copy are typically healthy carriers and do not show symptoms.
Can galactosialidosis be detected before birth?
Yes, for families where galactosialidosis has already been identified, prenatal diagnosis is possible. This involves testing samples obtained during pregnancy, such as through chorionic villus sampling or amniocentesis, to check for the genetic changes in the CTSA gene.
Is there a specific treatment for galactosialidosis?
Currently, there is no direct cure for galactosialidosis. Management focuses on supportive care to alleviate symptoms and improve quality of life. This can involve medication for seizures, therapies for developmental delays, and monitoring for organ complications.
What kind of doctors treat galactosialidosis?
Care for individuals with galactosialidosis is typically provided by a team of specialists. This often includes paediatricians, neurologists, metabolic specialists, ophthalmologists, audiologists, and genetic counsellors, depending on the specific symptoms present.
How rare is galactosialidosis?
Galactosialidosis is considered a very rare condition. The exact prevalence is not well established, but only a small number of cases have been reported worldwide since it was first described.
References
- Guertl B, Noehammer C, Hoefler G. Metabolic cardiomyopathies. International journal of experimental pathology. 2000. PMID: 11298185
- Sheth J, Patel P, Sheth F. Lysosomal storage disorders. Indian pediatrics. 2004. PMID: 15064514
- Cantz M, Ulrich-Bott B. Disorders of glycoprotein degradation. Journal of inherited metabolic disease. 1990. PMID: 2122119
- Gorelik A, Illes K, Mazhab-Jafari MT. Structure of the immunoregulatory sialidase NEU1. Science advances. 2023. PMID: 37205763
- Okamura-Oho Y, Zhang S, Callahan JW. The biochemistry and clinical features of galactosialidosis. Biochimica et biophysica acta. 1994. PMID: 8312369
- Bajpai S, Mandal K, Naranje K. Galactosialidosis presenting as non-immune hydrops. BMJ case reports. 2024. PMID: 39353673
- Hiraiwa M. Cathepsin A/protective protein: an unusual lysosomal multifunctional protein. Cellular and molecular life sciences : CMLS. 1999. PMID: 11212324
- Caciotti A, Catarzi S, Tonin R. Galactosialidosis: review and analysis of CTSA gene mutations. Orphanet journal of rare diseases. 2013. PMID: 23915561