IMPORTANT INFORMATION
The information on the Rare Awareness Rare Education (RARE) Portal is intended for educational purposes only and does not replace professional advice.
Rare diseases typically display a high level of symptom complexity and variability. Individuals diagnosed with the same rare disease may be impacted differently and each person’s experience is unique. Please seek support from qualified healthcare professionals to learn more about the most suitable care and support options for you.
If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.
Contributors
This page has been co-developed with RVA Partner, Fabry Australia.1
Quick Page Search:
Emergency Management | Clinical Care Guidelines | Synonyms | Summary | Personal Stories | Symptoms | Cause/Inheritance | Diagnosis | Treatment | Clinical Care | Research and Data | Rare Disease Organisation(s) | Support Services/Resources | Mental Health | Other | References
Emergency Management
Severe flares of nerve pain in Fabry Disease require special consideration if presenting to emergency departments, including:
- Notification of the treating Fabry clinician and/or pain specialist
- Awareness of the potential extreme severity and burning characteristic of the pain, spreading from peripheries to potentially whole body
- Identification of likely precipitants: exercise, temperature change, intercurrent illness
- Understanding that there may be no abnormal signs on physical examination, other than loss of temperature sensation or sweating
- Preferential use of neurolytic analgesics (such as gabapentin, pregabalin, carbamazepine, amitriptyline, duloxetine, tapentadol)
Clinical Care Guidelines
Australian Government Department of Health and Aged Care’s Guidelines for the treatment of Fabry disease through the Life Saving Drugs Program (LSDP) provides guidance for treating physicians with relevant specialist registration who wish to apply for their patients to receive access to Australian Government–subsidised treatment for Fabry disease through the LSDP.
Below are other clinical care guidelines from other countries; please note that this may not necessarily be relevant to the Australian context:
- Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients in France, published in 2019
- Fabry disease revisited: Management and treatment recommendations for adult patients developed by an international panel of Fabry disease experts, published in 2021
- OrphanAnesthesia has Anaesthesia recommendations for Fabry disease; please note this was last updated in 2019
Synonyms
Alpha-galactosidase A deficiency; Anderson-Fabry disease; Angiokeratoma corporis diffusum; Diffuse angiokeratoma; FD
Summary
Fabry disease is a lysosomal storage disorder.1,2 It is a genetic condition caused by changes in GLA gene on the X chromosome.3,4 Individuals with Fabry disease do not produce enough functional alpha-galactosidase (alpha-GAL) lysosomal enzyme, which is responsible for breaking down a type of fatty acid called globotriaosylceramide (Gb3 or GL3). This deficiency in alpha-GAL results in a continual build-up of Gb3 (and its metabolites, lyso-Gb3 or lyso-CTH) in the lysosomes, causing damage to the cells.2 This can affect many different parts of the body, resulting in a wide range of symptoms. As Gb3 continues to accumulate over time, it causes more and more damage to cells and organs, and may lead to further progression of the disease.
Fabry disease can affect both males and females, but symptoms in females tend to be more variable, ranging from no to severe symptoms.3 There are two subtypes of Fabry disease:2,5-6
- Classic Fabry disease – caused by complete (or close to complete) absence of alpha-GAL enzyme levels. This usually has an early onset of pain and rash, either in childhood or during adolescence, although this is sometimes mistaken as growing pains resulting in delayed diagnosis
- Late Onset Fabry disease – individuals have slightly higher alpha-GAL levels than those of the classic subtype. Symptoms present in adulthood, most commonly issues related to the heart, kidney, brain and its blood vessels, but the pain and rash of the classic form are not seen
Fabry Australia: Faber the Dragon is a wonderful children’s story (available as a book and in digital animation form) designed to explain, and help children and others understand, about Fabry’s disease.
Useful Links for Professionals
Fabry Australia: Understanding Fabry Disease
Fabry AustraIia: Information for Health Professionals
Online Mendelian Inheritance in Man (OMIM): #301500 – FABRY DISEASE
Human Phenotype Ontology (HPO): Fabry disease
Inborn Errors of Metabolism Knowledgebase (IEMbase): Alpha-galactosidase A deficiency
Personal Stories
Fabry disease varies between individuals, and each person’s experience is unique. Please visit Fabry Australia: Personal Stories to read the personal stories of people living with Fabry disease.
Symptoms
Fabry disease can affect different organs of the body.5 Symptoms vary widely between individuals and may worsen with age (progressive). The two subtypes of Fabry disease differ in terms of disease presentation:2,5-6
- Classic Fabry disease has an early onset, with specific signs that present early on the life as well as other symptoms that emerge later on in life
- Late onset Fabry only presents in adulthood; typically involves the heart and kidney, but may not include the symptoms that are usually seen during early childhood of the classic form
Early signs of Fabry disease include:1-3
- tingling, numbness and a burning sensation (acroparesthesias) particularly in the hands and feet
- pain, including severe, debilitating episodes of the intense, burning pain (Fabry crisis), which may be accompanied by fevers, body aches and fatigue
- dark red or purple skin lesions (angiokeratomas)
- whorl-like pattern in the cornea of the eye (cornea verticillate) that is not visible to eye but can be detected using specialised equipment by optometrists or eye specialists
- impaired sweating, such as no sweat (anhidrosis) or very little sweat (hypohidrosis) production, or in some cases, increased sweating (hyperhidrosis)
- gut (gastrointestinal) issues, including stomach discomfort, pain and diarrhea
Other symptoms include:1-3
- headaches and dizziness, including vertigo
- ringing sounds in the ear (tinnitus)
- hearing loss
- reduced kidney function and failure
- heart (cardiac) disease and complications
- issues with blood flow in the brain and risk of strokes
More information about the symptoms of Fabry disease can be found at Fabry Australia: Signs & Symptoms. Please also speak to your medical team to learn more about the symptoms and complications of Fabry disease.
Cause/Inheritance
Fabry disease is caused by a disease-causing genetic change in the GLA gene on the X chromosome and is a X-linked condition.3 Both males and females can be affected.
As males only have one X chromosome, they have one copy of the GLA gene (hemizygous), so if their GLA gene has the disease-causing genetic change, they will have Fabry disease. Females have two X chromosomes and two copies of GLA – if at least one of their copies has the disease-causing genetic change (heterozygous), they may be affected, with symptoms in females varying from severely affected to mild or no symptoms (asymptomatic).3
This is a heritable condition, which means it can be passed on to the next generation, even if the mother has no symptoms herself.
If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information on genetic counselling can be found on the National Services page and specific State and Territory Services pages on the RARE Portal.
Diagnosis
Diagnosis of Fabry disease may be made based on measurement of alpha-galactosidase enzyme activity in blood or white cells, as well as through genetic testing for changes in the DNA that have been associated with causing Fabry disease.1-3
Males with Fabry disease have low levels of alpha-galactosidase activity in their blood, whilst females may have low or normal levels and will often require genetic testing to confirm their diagnosis.1,3 Prenatal diagnosis is possible and may be offered to pregnant women who have Fabry disease.1
Treatment
There is currently no curative treatment for Fabry disease, but there are strategies to manage the symptoms, slow disease progression and improve quality of life.1 Therapies for Fabry disease in Australia include:1
- Enzyme replacement therapy (ERT) – regular blood infusions of the α‐galactosidase A (α‐Gal A) enzyme to increase the levels of α‐Gal A in cells
- Oral chaperone therapy – drug that is taken orally and acts as a chaperone; it binds to existing α‐Gal A enzymes in cells and enables the α‐Gal A to carry out its normal function in cells. This therapy is designed for individuals with specific types of DNA changes in their GLA gene known as amenable mutations and is not suitable for all individuals with Fabry disease
Two enzyme replacement therapy drugs and an oral chaperone therapy drug has been approved by the Therapeutic Goods Administration (TGA) for treatment of Fabry disease in Australia.1,7 These drugs are subsidised by the Life Saving Drugs Program (LSDP) for individuals who are eligible.7 More information about eligibility requirements for these therapies can be found at Australian Government Department of Health and Aged Care: Life Saving Drugs Program resources for Fabry disease.
Please speak to your medical team to learn more about the existing therapies for Fabry disease, including the suitability of the therapy and your eligibility.
Clinical Care
Healthcare professionals involved in the treatment of Fabry disease include general practitioners (GP), paediatricians, geneticists, cardiologists, dermatologists, nephrologists (kidney specialists), neurologists, ophthalmologists, ENT (ear, nose and throat) specialists, pain specialists, psychologists and psychiatrists.1,4 The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.
Information about Australian Fabry clinics can be found at:
Research and Data
Fabry Australia: Fabry Disease Clinical Trials has information about research and clinical trials relevant to Fabry disease, including substrate reduction therapy and gene therapy.
Please visit Australian Clinical Trials to learn more about clinical trials for Fabry disease in Australia; there may not be any clinical trials currently available.
Information regarding clinical trials for Fabry disease in other countries can be found at ClinicalTrials.gov; there may not be any clinical trials currently available.
It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.
Rare Disease Organisation(s)
Fabry Australia RVA Partner Australian Organisation
Website: https://www.fabry.com.au/
Contact form: https://www.fabry.com.au/contact/
Fabry Australia is a patient-run non-profit organisation founded in 1994. Fabry Australia’s mission is ‘Uniting and Supporting the Australian Fabry Community’.
Please note that RVA does not necessarily monitor or endorse each group/organisation’s operational governance.
Support Services/Resources
For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.
Mental Health
Please visit the ‘Mental Health’ sections listed on the National and State Services pages.
Other
Further information on Fabry disease can be found at:
- Fabry Australia: Resources
- healthdirect: Fabry disease
- Genetic and Rare Diseases (GARD) Information Center: Fabry disease
- National Organization for Rare Disorders (NORD): Fabry disease
References
- Fabry Australia. Accessed 2 April 2024. https://www.fabry.com.au/
- Fabry Australia. Understanding Fabry disease. 2017. 9p. https://www.fabry.com.au/wp-content/uploads/2022/08/Understanding-Fabry-Disease-brochure.pdf
- Mehta A, Hughes DA. Fabry disease. 2002. Updated 9 March 2023. In: Adam MP, Mirzaa GM, Pagon RA, et al. GeneReviews® [internet]. Seattle (WA): University of Washington Seattle. 1993–2023. Accessed 2 April 2024. https://www.ncbi.nlm.nih.gov/books/NBK1292
- Genetic and Rare Diseases (GARD) Information Center. Fabry disease. Accessed 2 April 2024. https://rarediseases.info.nih.gov/diseases/6400/fabry-disease
- Fabry disease. Accessed 2 April 2024. https://www.orpha.net/en/disease/detail/324
- National Organization for Rare Disorders (NORD). Fabry disease. Accessed 2 April 2024. https://rarediseases.org/rare-diseases/fabry-disease/
- Australian Government. Department of Health. Guidelines for the treatment of Fabry disease through the Life Saving Drugs Program. 2020; 4p. https://www.health.gov.au/sites/default/files/documents/2020/11/life-saving-drugs-program-fabry-disease-guidelines.pdf
Page Last Updated
29/04/2024 14:10