X-linked adrenoleukodystrophy (X-ALD) is a type of leukodystrophy. It is caused by changes in the ABCD1 gene, which leads to impaired function of the X-linked adrenoleukodystrophy protein which is known as ADLP. ADLP is involved in transporting very long-chain fatty acids in the body to be broken down.² In X-ALD, the fatty acids are not transported to be broken down but instead build up and cause damage in the brain and adrenal glands. This leads to the three main phenotypes (features) of X-ALD:^2-4

• Cerebral ALD (CALD) – characterised by neurological symptoms that affects behaviour, speech and ability to function normally. Approximately half to two-thirds of males with X-ALD develop CALD at some point of their lives.⁴ Symptoms most commonly develop in childhood (childhood CALD) but in some cases, may present in teenage years (adolescence CALD) or in adulthood (adult CALD). The symptoms tend to worsen quickly (rapidly progressive) and become very severe.
• Adrenomyeloneuropathy (AMN) – characterised by stiffness and weakness in legs, issues with walking, pain and numbness due to nerve damage (neuropathy), issues with the bowel and bladder. Symptoms usually develop in adulthood for males and females and worsen over time (progressive).
• Primary adrenal insufficiency – caused by damage to adrenal glands, resulting in the body not producing any, or enough, hormones that are important for regulating body processes such as metabolism and blood pressure. This can lead to adrenal failure (also known as adrenal crisis), which can be life-threatening. Symptoms may develop between early childhood (most common) to adulthood in males.

Not all individuals with X-ALD will develop these three features and symptoms vary widely between individuals, and may present at different stages in life even within one family. Males are at risk of developing CALD, AMN and primary adrenal insufficiency, while females can develop AMN at a later age than males, and are at very low risk of developing CALD and adrenal insufficiency.^4,5

In Australia, X-ALD has usually been diagnosed after symptoms develop. X-ALD is in the process of being added to Australia’s newborn bloodspot screening (NBS) programs. For more information, please visit the Australian Government Department of Health, Disability and Ageing: What is screened in the program page. Early detection and management are important to prevent life-threatening complications.³

Synonyms: ALD; X-linked ALD

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:43 X-linked adrenoleukodystrophy

ICD-11: 5C57.1 Disorders of peroxisomal alpha-, beta- or omega-oxidation

X-ALD can affect both males and females. The symptoms, age of onset and disease progression vary widely between individuals and differ between males and females. Males with X-ALD can develop cerebral ALD (CALD), adrenomyeloneuropathy (AMN) and primary adrenal insufficiency, which can present very differently between individuals and at different ages even within one family. Some males may develop CALD and/or primary adrenal insufficiency during childhood, whilst others may develop symptoms later in life, and may experience CALD, AMN and/or adrenal insufficiency, with some of the features developing as the condition progresses.⁶ Most males will develop AMN as they get older.

It was previously thought that females were not affected by X-ALD, but it is now recognised that females can be affected, mainly with AMN. However, symptoms usually develop in adulthood at a later age than males, and females are at a very low risk of developing adrenal insufficiency and cerebral ALD.⁵

Cerebral ALD (CALD)

This subtype of X-ALD most commonly presents in childhood, typically between the ages of four to eight years old and rarely before 3 years; this is known as childhood cerebral ALD (cCALD).³ Initial symptoms may appear as behavioural and learning difficulties. Children with CALD often have difficulty understanding and processing speech, sounds and written words, spatial disorientation (difficulty perceiving one’s position and motion relative to other things), visual issues, aggressive and impulsive behaviour. Individuals may also have seizures, and the condition can quickly progress to loss of ability to move and function normally, coma and early death.^1,3-4,6

In some cases, the symptoms may appear during adolescence (between 11-21 years of age) or later in life during adulthood, but the severe symptoms and disease progression are often similar to that of cCALD. It is rare for females to be affected by CALD.³

Adrenomyeloneuropathy (AMN)

Symptoms may include stiffness and weakness in the legs that worsen over time (spastic paraparesis), difficulties with walking that may affect how they walk (abnormal gait), numbness and pain caused by nerve damage (neuropathy), issues with the bladder and bowel, and sexual dysfunction.^1,3-6 Symptoms tend to develop in early adulthood and worsen over time. Whilst females were previously thought to just be carriers of the genetic variant and are unaffected, it is now believed that most females develop AMN symptoms over time.⁷

Primary adrenal insufficiency

Symptoms may include vomiting, weakness, fatigue, and coma.^1,3-4,6 If untreated, it can lead to adrenal failure (also known as adrenal crisis), which can be life-threatening. It has been reported that males can show symptoms at any age, but it often occurs in childhood, and may present before neurological symptoms develop. It is possible but rare for females to be affected by adrenal insufficiency and adrenal failure.³

There may be other symptoms and complications of X-ALD that have not been listed here. Please speak to your medical team to learn more about the symptoms and complications of X-ALD.

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.

X-ALD is a genetic condition. It is caused by disease-causing genetic changes (variants) in the ABCD1 gene located on the X chromosome.³ Most of the genetic variants are inherited (passed down) but some of the changes can occur by chance (de novo).

X-ALD can affect both males and females. As males only have one X chromosome, they have one copy of the ABCD1 gene, so if their ABCD1 gene has the disease-causing genetic variant, they will have X-ALD. Females have two X chromosomes and two copies of X-ALD 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). It was previously thought that females are just carriers of the genetic variant and are not affected; however, it is now recognised that many females will develop progressive symptoms.⁵

These genetic variants can be 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 about genetic counselling can be found at:

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

In Australia, X-ALD has usually been diagnosed after symptoms develop and involves testing of blood samples to look at the levels and ratios of specific fatty acids indicative of X-ALD, and confirmed by genetic testing.⁸ The specific features of X-ALD may be diagnosed via various tests, such as: ^9-10

• CALD can be detected by brain magnetic resonance imaging (MRI) and quantified with MR severity scoring system (Loes score)
• AMN can be diagnosed using family history and neurological examinations
• information regarding diagnostic tests for adrenal insufficiency can be found at Addison’s disease (Primary adrenal insufficiency) .

X-ALD is in the process of being added to Australia’s newborn bloodspot screening (NBS) programs. Both male and female babies will be screened for X-ALD once it has been added to the NBS programs. For more information about the program, please visit:

• Australian Government Department of Health, Disability and Ageing: What is screened in the program page

Please speak to your medical team to learn more about the available pathways for diagnosis of this condition.

There is currently no curative treatment for all the subtypes of X-ALD, but there are therapeutic options for CALD and adrenal insufficiency and strategies to manage AMN.⁹ The overall management of X-ALD and its specific aspects require a multidisciplinary care team. The multidisciplinary interventions should also include psychological and social support.¹¹ As diagnosis may happen before symptoms present, it is important for diagnosed individuals to undergo regular screening and monitoring for the different features of X-ALD to enable early intervention.

For CALD, haematopoietic stem cell transplantation (HSCT) from a bone marrow donor has been shown to stop progression of CALD and prevent life-threatening complications, especially if treated at an early stage.^12-13 Regular monitoring for CALD with brain imaging surveillance (using brain MRI) is crucial for early diagnosis of CALD and treatment.^9-10,12 International guidelines have recommended that for males, a baseline scan is performed at 2 years old, and scans are done every 6 months between the ages of 2-12 years old, following by yearly scans after turning 12 years old.⁹ Routine screening is not recommended for females, who are at very low risk of CALD.

Treatment of adrenal insufficiency involves long-term hormone replacement therapy⁹ to prevent adrenal crisis, which is a medical emergency. People with X-ALD with adrenal insufficiency should have a sick day plan and a supply of an injection of hydrocortisone for emergencies. Regular assessment and monitoring of adrenal function is important to detect onset of adrenal insufficiency and enable timely treatment to avoid the life-threatening adrenal crisis. International guidelines have recommended that for males, screening should commence within the first 6 months of life and done every 3-6 months until 10 years of age and done yearly after that.⁸ Routine screening is not recommended for females.

Management of AMN is focussed on managing symptoms (symptomatic management), maximising function, improving quality of life, and preventing complications.^4,9 This may include managing pain and spasticity, therapy to maintain strength and range of movement, treating bowel and bladder issues as well as monitoring and management of bone health.^9,12 It has been recommended that all individuals (males and females) diagnosed with X-ALD are counselled and made aware of the specific symptoms of AMN at diagnosis (or when detected to carry a disease-causing genetic variant of X-ALD) to enable early identification of AMN when symptoms develop, and regular follow-ups have been recommended for individuals who have developed AMN.⁹

According to international recommendations, additional management recommendations for X-ALD as a whole include informing individuals diagnosed with ALD about the option of family screening and potential benefits of prenatal and preimplantation diagnostic options, and classifying females with X-ALD genetic variant as “asymptomatic/presymptomatic” or “symptomatic women with ALD” in place of the terms “heterozygotes” or “carriers”.⁹

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. For many rare diseases, treatment options may be limited. Participation in a clinical trial may provide access to new or emerging therapies.

Healthcare professionals involved in the care of individuals with X-ALD may include general practitioners (GP), paediatricians, geneticists, genetic counsellors, endocrinologists, neurologists, urologists, gastroenterologists, physiotherapists, occupational therapists, speech therapists, pain specialists, psychologists, and others. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Clinics:

• White Matter Disorders Clinic  at the Royal Children’s Hospital (Victoria) runs on a monthly basis. The clinic provides comprehensive assessment and diagnostic testing where needed for children with leukodystrophies and white matter disorders. A GP or specialist referral is required.
• The Adult Leukodystrophy Clinic at the Westmead Hospital (New South Wales) is coordinated through the Department of Genetic Medicine and runs every second month. The specialists in the clinic can provide assessment, diagnostic testing and management for adults with suspected or confirmed leukodystrophies. A GP or specialist referral is required.

Adult men and women with X-ALD can be referred to the adult metabolic genetics clinic that covers the state or territory in which they live. Some clinics may see adult men with X-ALD regularly, while women may be linked in with a local specialist for symptom management. This will depend on each state and service.

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.

This may not be applicable to all rare diseases but for many, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness and is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. If this is relevant to you and you wish to find out more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

The following recommendations are 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:

• International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy: A Consensus-Based Approach outlines best-practice recommendations for diagnosis, clinical surveillance, and treatment of patients with ALD developed by 28 international ALD experts; published in 2022
• Use of Brain MRI in Cerebral Adrenoleukodystrophy recommends practical guidelines on the use and interpretation of MRI techniques in ALD for a real-world setting, developed by thirty experts from 9 countries; published in 2026
• Adrenoleukodystrophy: Guidance for Adrenal Surveillance in Males Identified by Newborn Screen outlines clinical recommendations developed by a working group for ALD within the United States of America Pediatric Endocrine Society Drug and Therapeutics/Rare Diseases Committee; published in 2018
• Newborn screening for X-linked adrenoleukodystrophy in New York State: Diagnostic protocol, surveillance protocol and treatment guidelines outlines the first diagnostic protocol for X-ALD newborn screening; published in 2015. It was developed in preparation for implementation of X-ALD newborn screening in New York State, United States of America.

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.

In addition, individuals, their parents, families and carers often develop extensive expertise on their specific rare disease. It is important to recognise that they can contribute valuable knowledge about their rare condition. Rare diseases often impact individuals differently, so it’s important to consider a person’s lived experience.

The RARE Portal’s Primary adrenal insufficiency page (Emergency Management section) covers information about adrenal crisis, which is a medical emergency.

The Australian Leukodystrophy Clinical and Research Program is a collaboration between medical research institutes, hospitals and universities around Australia including: the Royal Children’s Hospital, the Murdoch Children’s Research Institute, the University of Queensland, the University of New South Wales and the Women’s and Children’s Hospital (South Australia). They also maintain The Australian Leukodystrophy and White Matter Disorders Registry.

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. For more information, please visit the RARE Portal’s Considerations for Participating in Health and Medical Research page.

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 research, including clinical trials,  with your medical team to determine suitability and eligibility.

Australian Organisation:
Leukodystrophy Australia 
Website: https://leuko.org.au/ 
Leukodystrophy Australia is the national peak organisation representing people impacted by leukodystrophy. Leukodystrophy Australia collaborates with local, national and international stakeholders to advance the care of their members, improve quality of life and ultimately seek a cure for leukodystrophy.

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.

X-ALD varies between individuals, and each person’s experience is unique.

Leukodystrophy Australia: Our People Our Stories has personal stories of people living with leukodystrophy.

Personal story shared with RVA: Ryan’s story

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 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 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 X-ALD can be found at:

• National Organization for Rare Disorders (NORD): X-Linked Adrenoleukodystrophy
• Genetic and Rare Diseases (GARD) Information Center: Adrenoleukodystrophy
• ALD Connect: What is Adrenoleukodystrophy (ALD)?

GeneReviews^®: X-Linked Adrenoleukodystrophy

ORPHA:43 X-linked adrenoleukodystrophy

Online Mendelian Inheritance in Man (OMIM): #300100 – Adrenoleukodystrophy; ALD

International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy: A Consensus-Based Approach outlines best-practice recommendations for diagnosis, clinical surveillance, and treatment of patients with ALD developed by 28 international ALD experts; published in 2022

Clinically Relevant Outcome Measures in Women With Adrenoleukodystrophy – scoping review of clinically relevant assessment scales that have been utilized to capture disease manifestations in women with adrenoleukodystrophy

ALD Connect: What is Adrenoleukodystrophy (ALD)?

This page has been co-developed by Rare Voices Australia (RVA)’s RARE Portal team in consultation with Leukodystrophy Australia and input from Dr David Manser (Neurologist and Staff Specialist, Department of Genetic Medicine at Westmead Hospital, NSW), published on 16 June 2026.

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.