Adrenoleukodystrophy is a rare condition associated with abnormalities in myelin, the white matter that protects nerve fibers in the spinal cord and brain. It occurs due to a mutation on the X chromosome.
Adrenoleukodystrophy is a serious condition. It can cause severe neurological disabilities and may result in death. Supportive care may help provide relief from symptoms.
This article reviews adrenoleukodystrophy types, symptoms, causes, and more.
A note about sex and gender
Sex and gender exist on spectrums. This article will use the terms “male,” “female,” or both to refer to sex assigned at birth. Click here to learn more.
Adrenoleukodystrophy is broken down into types based on:
- age of onset
- symptoms
- organs involved
- how it was inherited
Adrenoleukodystrophy includes
X-ALD is the most common type. It has an X chromosome–linked inheritance pattern. There are three additional subtypes based on the affected organs and age of onset:
- Childhood cerebral ALD: This often starts between ages 3 and 10 years. It presents with developmental regression.
- Addison’s disease: This involves the adrenal glands. It causes a decreased function of cortisol and aldosterone.
- Aadrenomyeloneuropathy: This occurs when a person is in their 20s. It is often a milder form.
N-ALD has an autosomal recessive inheritance pattern. It often presents shortly after birth. Infants with mild symptoms may have a delayed diagnosis.
N-ALD is not true adrenoleukodystrophy. It is a distinct condition.
Symptoms vary based on the type of adrenoleukodystrophy.
X-ALD
X-ALD symptoms also vary based on the subtype.
Childhood cerebral ALD
Development regression is a main feature of childhood cerebral ALD.
A child with this form may develop as expected until they reach
This form is often progressive. It can lead to continued neurological symptoms, including:
- vision loss
- impaired balance
- inability to walk
- confusion or decline in thinking skills
- loss of ability to speak or communicate
- seizures
- coma
- death
Addison’s disease
Addison’s disease causes a decrease in the adrenal glands’ production of the hormones cortisol and aldosterone.
A decrease in cortisol can cause weakness and hypoglycemia, or low blood sugar.
A decrease in aldosterone can cause:
- low sodium in the blood
- fatigue
- hypotension (low blood pressure)
- dehydration
It may also cause skin hyperpigmentation.
Learn more about the symptoms of Addison’s disease.
Adrenomyeloneuropathy
Adrenomyeloneuropathy typically causes milder symptoms. It does not develop until adulthood. Symptoms may include:
- unbalanced gait
- walking difficulties
- bladder or bowel sphincter dysfunction
N-ALD
When a baby develops N-ALD, symptoms can present shortly after birth. They may include:
- issues with vision, such as cataracts or optic nerve dysplasia
- hearing issues
- seizures
- failure to thrive
- hypotonia (decreased muscle tone)
- jaundice (yellowing of the eyes and skin)
- enlarged liver
- facial dysmorphism, such as hypertelorism (increase in space between bony structures of the eyes) and flat midface
In
More specifically, the gene involved is ABCD1. This gene plays a role in the very-long-chain fatty acids (VLCFA) transport system and interferes with the metabolism of VLCFA. This leads to an abnormal buildup of VLCFAs in vital organs, such as the brain and spinal cord.
N-ALD may have an autosomal recessive inheritance pattern. N-ALD interferes with any of the PTS1 receptors, including PXR 1, PEX1, PEX 10, or PEX 13 genes.
A person inherits a mutated X chromosome from their parents.
The X gene is one of two sex chromosomes. Males have an X and a Y chromosome. Females have two X chromosomes.
Males inherit an X gene from the parent with two X chromosomes and a Y gene from the parent with XY chromosomes. Any male who inherits an X chromosome with the mutation will develop ALD.
Females inherit a copy of the X gene from each parent. Females who have one copy without the mutation and one copy with the mutation will not usually develop symptoms of ALD, but they might develop mild symptoms at an advanced age.
Females with the gene mutation have a 50% chance of passing the condition to their children.
In some U.S. states, doctors now screen for X-ALD as part of a check for cases of genetic disorders in newborns. Screening can help doctors treat the condition before symptoms start.
If doctors do not diagnose the condition through screening, they may order tests if a person has potential symptoms of the condition.
To diagnose the condition, doctors
- increased VLCFA plasma concentration
- decreased red blood cell plasmalogen (type of lipid for brain function) concentration
- increased concentration of pipecolic and phytanic acid concentration in both plasma and fibroblasts (cells that help create connective tissue)
Diagnosis also requires an MRI of the brain. This imaging test helps a doctor see whether certain features in the brain indicate adrenoleukodystrophy.
The treatments for X-ALD and N-ALD can manage symptoms but
A doctor may recommend supportive care to help provide some relief. This can include:
- respiratory support
- a feeding tube for providing nutrition
- occupational therapy
People with Addison’s disease may benefit from medication, such as corticosteroid and mineralocorticoid replacement therapy. This therapy helps replace substances that the adrenal gland is not producing.
People with mild symptoms or who do not have any symptoms may benefit from a hematopoietic cell transplant (HCT). A doctor can provide more information about HCT if they feel it is a suitable treatment.
Further research is necessary to investigate additional therapies that may help improve outcomes for more people.
X-ALD is the most common type of adrenoleukodystrophy. It affects between 1 in 10,000 and
N-ALD occurs in around
A person often shows signs of childhood cerebral ALD between the ages of
People of Latino or African descent have a higher chance of developing ALD.
Males have a higher chance of developing a severe form of the condition because it is an X-linked condition. Females tend to have mild symptoms that appear later in life.
N-ALD does not affect males and females differently.
The
Life expectancy can depend on the type of ALD. In cases of childhood cerebral ALD, a person typically only survives for a few years after symptoms begin.
A doctor can provide more accurate information about outlook based on individual circumstances.
Adrenoleukodystrophy (ALD) is a rare condition that can cause neurological disability and death. It is typically an X chromosome–linked condition.
Because it is an X-linked condition, males develop more severe symptoms than females. Females are typically asymptomatic carriers, or they might develop only mild symptoms late in life.
Treatment often focuses on relieving symptoms and not curing the condition. Future studies may look further into better, more effective treatment options for people with the condition.