What is ALD?

As the Wiener family knows from first-hand experience, initially learning about ALD can be overwhelming. Cure ALDs aim is to be a guide in navigating the key information sources in your ALD journey as you are getting started.

X-linked Adrenoleukodystrophy (ALD) is a rare genetic disease affecting 1 in 17,000 people, impacting the brain, spinal cord, or adrenal glands with varying severity. Young boys face the most devastating form—childhood cerebral ALD—which can be fatal without early intervention.

Research progress toward curative or preventative treatments remains frustratingly slow, hampered by limited funding for rare disease research, particularly as federal support has been reduced in recent years.

While treatment options exist for some manifestations (stem cell transplants for cerebral ALD and cortisol replacement for adrenal insufficiency), there is no cure or preventative treatments.

Adrenoleukodystrophy Explained

For a complete overview, check out this 9 minute video from Youreka Science and ALD Connect.

Understanding ALD

Checkout these great resources for a deeper dive into the understanding of ALD.

ALD Connect

They provide the most comprehensive explanation of Adrenoleukodystrophy (ALD).

Adrenoleukodystrophy Explained

For a complete overview, check out this 9 minute video from Youreka Science and ALD Connect.

ALD Phenotypes

Learn more about the different phenotypes and how differently they progress over time.

Phenotypes and Current Treatments

ALD manifests differently across individuals, with symptoms ranging from mild to severe over time. The distinct form of the ABCD1 gene mutations can be classified into four primary phenotypes (collection of symptoms):

Asymptomatic
Adrenomyeloneuropathy (AMN)
Adrenaline Insufficiency
Cerebral ALD (CALD)

All phenotypes impact both boys and men. Women with ALD may experience neurological symptoms, similar to those experienced by men with AMN. Individuals may exhibit different or even multiple phenotypes over their lifetime, making early diagnosis and ongoing monitoring essential.

Symptoms
None
Treatment
Newborn screening - just after birth, a few drops of blood are collected from a baby’s heel and analyzed for elevated VLCFA levels.

Boys should also be seen by a neurologist to monitor for the development of cerebral disease with an MRI every 6 months from age 2-12, and shifting to annual MRIs after age 12.
Symptoms
Common symptoms include stiffness, weakness, and pain in the legs, which typically start gradually and may worsen over time. The nerves controlling the bladder, bowel, and sexual function can also be affected, leading to a range of complications. Mobility may gradually deteriorate, and while some individuals may eventually require a wheelchair, others may never reach that point. It’s important to note that the symptoms and progression of AMN can differ significantly from person to person.
Treatment
Symptom management is a key aspect of care. This may include medications to alleviate spasticity, manage bladder and bowel dysfunction, and address other neurological symptoms. Physical and occupational therapy can help maintain mobility and improve quality of life.
Symptoms
Regular monitoring is crucial. Failure to promptly recognize and treat adrenal insufficiency can lead to symptoms such as very low blood pressure, fainting, altered mental status, and seizures.
Treatment
Manageable with oral medications. Daily steroid replacement therapy, with dosage adjustments made during periods of stress or illness.
Symptoms
In boys, early signs may include difficulties with vision, hyperactivity, and challenges in learning, which can sometimes be mistaken for conditions like ADHD. Behavioral changes, such as irritability or social withdrawal, may also be present, along with clumsiness and a decline in previously acquired skills like writing or speech comprehension. Symptoms become more severe as the disease progresses including blindness, deafness, seizures, and the loss of muscle control leading to an inability to walk or talk, and ultimately death.

In adult men, signs begin with subtle cognitive or psychiatric symptoms. These can include personality changes, memory loss, or emotional instability. The disease progresses relentlessly if untreated, leading to severe neurological impairment, a vegetative state, and eventually death.
Treatment
Diagnosed through brain MRI. Allogeneic hematopoietic stem cell transplant (Allo-HSCT), also known as bone marrow transplant (BMT), has long been used for eligible boys with cerebral ALD to halt disease progression.

Gene therapy is an alternative to allo-HSCT. Gene therapy involves removing a patient’s bone marrow cells from their body and modifying them in the lab so that the cells become capable of producing the ALD protein.