Family History

Sibling with unexplained death or neurologic abnormality (such as multiple sclerosis); Addison’s disease; or alternatively, lack of a suggestive family history
Learning disabilities, attention disorders, behavior problems often reported in family members

Disease Course
Onset or marked worsening of symptoms; preschool and early years often normal
Behavioral/developmental symptoms chronic, often noticed when child begins school; ADHD diagnosis requires onset of symptoms before age 7

Comorbidity
Symptoms of multiple externalizing and internalizing disorders (i.e. depression or anxiety) common; neurological signs such as seizures often present; adrenal insufficiency often present
Symptoms of multiple externalizing and internalizing disorders (i.e., depression or anxiety) are less common; adrenal insufficiency not usually found


Adapted from Ievers CE, Brwon RT, McCandles SE et al. J Dev Behavior Pediatrics. 1999;20(1):31-35.

What Should Physicians Look For?

Some key clues that should alert physicians to consider the possibility of ALD include:

A family history of significant medical conditions, early morbidity, or symptoms of behavioral or developmental disorders that appear to be genetic;

Signs of abnormal development in the child;

Changes in the child’s functioning, such as declines in cognition, learning, behavior, or emotional regulation;

Rapid acceleration of such changes;

Late onset of symptoms that typically occur earlier in childhood, such as attention or learning problems;

Visual-spatial or visual-perceptual difficulties; and

Lack of sustained response to symptomatic therapies.

Physicians may consider referring to the following table when ALD is included as a differential diagnosis:


Degenerative Disorders
(e.g., ALD)
Developmental/Behavioral Disorders (e.g., ADHD)

What Should Parents and Families Look For?

It is very difficult to differentiate ALD from other conditions, such as ADHD, epilepsy, autism, and other learning disabilities, particularly if you are not aware that a genetic predisposition to the disease runs in your family. However, if you notice some of the following things, be sure that your child’s physician is considering the possibility of ALD—especially if you have a family history of neurological problems:

Late-onset ADHD or other attention problems.
A child with ADHD usually shows attention problems in preschool or early school years, while ALD symptoms appear between ages six and 10. If your son had no trouble paying attention in kindergarten but is suddenly developing problems in second grade, mention this to your doctor.

Lack of response to medications for ADHD.
If your child has been receiving a stimulant medication for ADHD and has not responded, your doctor will probably suggest a change of dose or change of medication. Ask for a blood test for ALD and a brain MRI at the same time.

Adrenal insufficiency.
If your doctor diagnoses your child with Addison’s disease, a test for ALD should be automatic, since ALD is the most common reason for Addison’s disease in childhood.

Problems with vision.
Visual impairment, caused by lesions on the optic tract, is characteristic of early seen ALD, and is frequently misdiagnosed.

Diagnosing ALD

It is essential to diagnose ALD as early as possible. All the evidence indicates that the two currently available treatments for the disease—Lorenzo’s oil and stem cell transplantation—only work during a very narrow window either before symptoms develop, or very early after their onset. Once the disease has progressed and symptoms have become severe, there are currently no treatments that can replace the lost myelin and the only treatments available are palliative.

Unfortunately, cases of ALD are often missed or misdiagnosed during the critical period of early onset. This is often because diagnosing ALD can be a tremendous challenge for many physicians. The earliest symptoms of the disorder in childhood can easily be mistaken for a number of other, much milder and much more common developmental and behavioral problems, such as attention deficit disorder (ADD/ADHD) or learning disabilities.