An Overview of Adrenoleukodystrophy (ALD)

Adrenoleukodystrophy (ALD) is an inheritable degenerative disorder in which the membrane around nerve cells, called myelin, begins to break down. As the disease progresses, ALD can cause an array of neurologic symptoms, including hyperactivity, seizures, loss of motor skills, speech and hearing problems, blindness, and, eventually, non-responsive dementia. Brought to the world's attention via the 1992 film Lorenzo's Oil, ALD is sometimes also called Lorenzo's Oil disease.

ALD is an extremely rare genetic disorder affecting one in every 20,000 to 50,000 individuals worldwide, and mostly males. It can be definitively diagnosed with a genetic test able to detect a mutation known as ABCD1 on the X chromosome. The same test can be used for prenatal, newborn, and preconception screening.

While the onset of symptoms can range from early childhood to the later adult years, younger boys are the most severely affected with death typically occurring anywhere from one to 10 years following the first appearance of symptoms.

Nerve fibres, light micrograph
PASIEKA / Getty Images

Inheritance Patterns

The symptoms of ALD can vary by sex and the stage of life when they first appear. ALD is an X-linked recessive disorder, meaning that the genetic mutation is located on the X chromosome, one of two that determine a person's sex. Females have two X chromosomes (XX), and males have one X and one Y chromosome (XY).

Generally speaking, males are most affected by an X-linked recessive disorder, while women are generally carriers of the mutation. There are several reasons for this:

  • If a couple has a boy, the mother will contribute the X chromosome with the ABCD1 mutation, while the father will contribute the Y chromosome. Since most mothers will have one affected X chromosome and one normal X chromosome, a boy will have a 50/50 chance of inheriting ALD.
  • If the couple has a girl, it is extremely rare that the mother and father will both contribute the ABCD1 mutation. In most cases, the girl will have one normal X chromosome. In this case, the disease may develop but be far milder since the normal X chromosome will dominate over the X chromosome with the recessive ABCD1 mutation.


A mutation of the ABCD1 gene causes the depletion of a protein that the body needs to break down fat molecules known as very long-chain fatty acids (VLCFA). The resulting accumulation of VLCFA appears to have an inflammatory effect, gradually destroying the myelin sheath of the cells that comprise the white matter of the brain. It also directly impairs the function of the adrenal glands and testicles, both of which produce hormones.

Why these cells are affected and not others is still unclear given that the VLCFA concentration will be the same throughout all the body. Moreover, high VLCFA concentrations in the blood don't necessarily correspond to ALD symptoms. In fact, some people with high concentration will have milder symptoms, while women will sometimes have completely normal VLCFA values in their blood.

Generally speaking, though, 99 percent of males with the ABCD1 mutation will have abnormal VLCFA concentrations.


Even if a child inherits the ABCD1 mutation, the symptoms they may experience can vary dramatically. In the end, there can be many different variations of the mutation (genotypes), each of which corresponds to a different expression of the disease (phenotype).

While scientists don't yet fully understand these variations, they have been able to describe the phenotypes based on shared characteristics in males and females, specifically the age of onset and the typical course of the disease.

Males ALD Phenotypes

Around 35 percent of ALD cases develop before the age of 11. While men ages 21 to 37 represent an even larger group (46 percent), the manifestations of the disease will often be less severe and, in some cases, may never progress beyond a certain stage.

The four most common male phenotypes can be broadly described as follows:

  • Childhood cerebral ALD occurs between the ages of 4 and 8 and is associated with a decline in neurologic function, including attention deficit disorder, emotional instability, hyperactivity, and disruptive behaviors and leading to seizures, spasticity, incontinence, a loss of motor skills, blindness, and eventual non-responsive dementia.
  • Adolescent ALD occurs between 11 and 21 with the same symptoms as childhood cerebral ALD, albeit developing at a slower rate.
  • Adrenomyeloneuropathy (AMN) occurs between 21 and 37 and is characterized by progressive nerve pain (neuropathy), impaired motor and sensory function, and sexual dysfunction. About 40 percent will progress to cerebral ALD.
  • Adult ALD is a type that all of the hallmarks of cerebral ALD, but without the preceding AMN symptoms.

Many boys with ALD under the age of 8 will not experience the cerebral form of the disease but instead develop Addison's disease, a disorder in which the adrenal glands do not produce enough hormones for the body to function normally. Also known as adrenal insufficiency, the symptoms tend to be non-specific and include fatigue, nausea, a darkening of the skin, and dizziness upon standing.

There are some individuals with the ABCD1 mutation who do not develop any ALD symptoms at all. It is difficult to say how many there are given that ALD is usually only diagnosed if symptoms appear. It is only if the newborn screening is performed that a child may be identified and tracked (more on testing below).

Female ALD Symptoms

ALD symptoms in females tend to develop only in adulthood and will be considerably milder than males. In fact, most women under 30 will be entirely without symptoms. The only exception is Addison's disease, which can strike at any age but affects only around 1 percent of women with ALD.

It is usually only after age 40 that the characteristic symptoms first appear, which are broadly classified by the following phenotypes:

  • Mild myelopathy will affect 55 percent of women with ALD, causing abnormal and sometimes uncomfortable sensations in the legs, as well as exaggerated reflexes.
  • Moderate to severe myelopathy, affecting 15 percent of women, is characterized by symptoms to male AMN, albeit milder.
  • Cerebral ALD only affects around 2 percent of women with ALD.


ALD can be difficult to spot since the disease has so many variations and is often confused with other more common disorders, particularly in the early stages. This includes attention-deficit/hyperactivity disorder (ADHD) and multiple sclerosis (MS), another disease caused by nerve demyelination.

If ALD is suspected, the first step would be to measure the concentration of VLCFA in a sample of blood. This is performed with a test known as gas chromatography-mass spectrometry, which can detect and measure specific compounds based on their light-absorbing properties. If VLCFA values are high, genetic testing would be performed to confirm the presence of the ABDC1 mutation.

If cerebral symptoms are identified, an imaging test known as magnetic resonance imagining (MRI) may be ordered. An MRI, which uses magnetic fields and radio waves to visualize organs, is able to measure minute changes in the white matter of the brain. The changes, if any, can be measured by a system known as the Loes score which rates the severity of brain abnormalities on a scale of 0 to 34. Any score above 14 is considered severe.

ALD Screening

Genetic testing can also be used to screen pregnant women and newborns for the ABCD1 mutation. ALD was added to the Recommended Uniform Screening Panel (RUSP), the federal list of genetic diseases recommended for state newborn screening tests, in 2016.

The challenge of screening, of course, is that the presence of the ABCD1 mutation cannot predict how severe the symptoms if any, might be. On the other hand, it may help ensure that treatment is delivered immediately if and when symptoms develop.

The genetic test can also be used for preconception screening. In such case, if a woman tests positive for the ABCD1 mutation, meaning that one of her X chromosomes carries the ABCD1 mutation, the couple will have a 50 percent chance of having a child some form of ALD. If the mother tests positive, the father can also be tested, but it is extremely unlikely that he, too, would carry the ABCD1 mutation unless he has ALD and has not been diagnosed.


Early identification of the ABCD1 mutation is vital to delivering an effective treatment of ALD. Of the treatments currently used, only a blood stem cell transplant (also known as a hematopoietic stem cell transplant) is able to stop the myelin loss central to the development of cerebral ALD.

Meanwhile, hormone replacement therapy can be used to treat Addison's disease. For its part, Lorenzo's oil, a dietary intervention, remains a highly controversial treatment with little in the way of clinical evidence to support its use.

Stem Cell Transplant

A hematopoietic stem cell transplant (HSCT) is a complex process in which a child with ALD would first be exposed to high-dose chemotherapy and possibly radiation to weaken the immune system so that it does not reject the donated stem cells. Afterward, stems cells from a matched donor would be harvested from either bone marrow or circulating blood and transfused into the recipient.

As the bone marrow begins to "adopt" these cells, it will start producing the proteins able to break apart the accumulated VLCFA, usually within months or even weeks.

While HSCT has been shown to prolong life and prevent the more devastating aspects of ALD, the effectiveness of the treatment can vary. Moreover, the process itself is so demanding that some children, stripped of their immune defenses, will die of infection before the benefits of treatment can be achieved. It is for this reason that HSCT is only performed if symptoms of cerebral ALD develop, namely in boys or men.

The first successful transplant took place in 1990, and there have many others since. Boys respond better than adults and usually demonstrate marked improvement in their Loes scores (a rating of the severity of abnormalities in the brain found on MRI). While a transplant doesn't necessarily improve all symptoms, it does appear to prevent further deterioration of neurological or psychiatric function, according to research from the University of Minnesota.

The one thing that HSCT does not restore is adrenal insufficiency.

When performed in men, HSCT appears to stop rather than reverse symptoms of ALD. While mental function is usually stabilized, motor functions tend to deteriorate despite treatment. Moreover, according to a study from the Hospital Necker-Enfants Malades in Paris, the risk of transplant-related death is high. Of the 14 adult males included in the research, six died as of a direct result of a post-transplant infection.

Hormone Replacement Therapy

Since adrenal insufficiency, a.k.a. Addison's disease, cannot be reversed with a stem cell transplant, hormone replacement therapy (HRT) is needed to replace hormones not produced by the adrenal glands.

Depending on the severity of symptoms, this may involve:

  • Oral corticosteroid drugs like prednisone or Cortef (hydrocortisone) taken one to three times daily
  • Oral Florinef (fludrocortisone acetate) taken once or twice daily

Corticosteroid injections may be given if you cannot tolerate the oral versions. Side effects of HRT include:

  • Nausea
  • Headaches
  • Insomnia
  • Mood changes
  • Slow wound healing
  • Easy bruising
  • Muscle weakness
  • Menstrual changes
  • Spasms
  • High blood pressure
  • Osteoporosis
  • Glaucoma

Lorenzo's Oil

Lorenzo's oil was a treatment developed by Augusto and Michaela Odone in 1985 as a last-ditch effort to cure their son, Lorenzo, who had already experienced severe cerebral symptoms of ALD. The treatment, comprised of rapeseed oil and olive oil, was initially believed to halt, and even reverse, the course of the disease.

While Lorenzo's oil can, in fact, normalize VLCFA concentrations in the blood, its use has not been shown to either slow neurologic deterioration or improve adrenal function. This suggests that VLCFA plays less of a role in the progression of the disease once it has been established.

Additionally, there is no evidence that Lorenzo's oil can either prevent or delay the development of ALD in people with the ABCD1 mutation who do not have symptoms, further highlighting how much we still need to learn about the disease.

13 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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Additional Reading

By Mary Kugler, RN
Mary Kugler, RN, is a pediatric nurse whose specialty is caring for children with long-term or severe medical problems.