Fabry disease is a lysosomal storage disorder.¹ It is a genetic condition caused by changes in GLA gene on the X chromosome.^2,3 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 cells in the body, causing damage to the cells.¹ 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:^1,4,5

1. 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
2. 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.

Synonyms: Alpha-galactosidase A deficiency; Anderson-Fabry disease; angiokeratoma corporis diffusum; diffuse angiokeratoma; FD

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:324 Fabry disease

ICD-11: 5C56.01 Fabry disease

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:^1,4,5

1. 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
2. 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:^1-2

• 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:^1-2

• 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 speak to your medical team to learn more about the symptoms and complications of Fabry disease.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

Fabry disease is caused by a disease-causing genetic changes (variants) in the GLA gene on the X chromosome (X-linked condition).²

Both males and females can be affected. As males only have one X chromosome, they have one copy of the GLA gene, so if their GLA gene has the disease-causing genetic variant, they will have Fabry disease. Females have two X chromosomes and two copies of the GLA gene – if at least one of their copies has the disease-causing genetic variant, they may be affected, with symptoms in females varying from severely affected to mild or no symptoms (asymptomatic).² These genetic variants can be inherited (passed on to the next generation). More information on X-linked inheritance pattern can be found at Centre for Genetics Education: X-linked inheritance.

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 at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

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.^1-2

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.^1,2 Prenatal diagnosis is possible and may be offered to pregnant women who have Fabry disease.

Please speak to your medical team to learn more about the available diagnostic pathways for Fabry disease.

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:

• 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.⁶ The enzyme replacement therapy drugs are subsidised by the Life Saving Drugs Program (LSDP) for individuals who are eligible,⁶ whilst the oral chaperone therapy drug is available through the Pharmaceutical Benefits Scheme (PBS) through a prescription from a physician with expertise in the management of Fabry disease.⁷ More information about eligibility requirements for these therapies can be found at Australian Government Department of Health, Disability and Ageing: Life Saving Drugs Program resources for Fabry disease.

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

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.³ 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:

• Fabry Australia: Adult Clinics
• Fabry Australia: Paediatric Clinics

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.

The following guidance is available from international experts outside Australia; however, there may be information that is not relevant or applicable to the Australian context, and may not be up to date:

• Consensus recommendations for the treatment and management of patients with Fabry disease on migalastat: a modified Delphi study – recommendations developed by a multidisciplinary panel comprised 14 expert physicians across nine specialties and two patients with Fabry disease
• 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

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

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

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Please note that RVA does not necessarily monitor or endorse each group/organisation’s operational governance and activities.

Australian Organisation:

Fabry Australia
Website: https://www.fabry.com.au/

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 monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

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.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

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.

People living with a rare disease, including families and carers, often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many people find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

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

• Fabry Australia: Understanding Fabry Disease
• Fabry AustraIia: Information for Health Professionals
• GeneReviews^®: Fabry Disease
• 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

This page has been co-developed by Rare Voices Australia (RVA)’s RARE Portal team in consultation with Fabry Australia.

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.