Adrenoleukodystrophy (ALD)

What is Adrenoleukodystrophy (ALD)?

Adrenoleukodystrophy (ALD) is a condition of major focus for our research team. ALD is an X-linked disorder that causes adrenal insufficiency and neurologic complications. A severe form with rapidly progressing brain disease develops in approximately one third of boys with ALD, usually between the ages of 4 and 10 years of age. This form is called “cerebral ALD.” Cerebral ALD causes progressive problems with visual and auditory processing, motor function and cognition. Without treatment, cerebral ALD is nearly always fatal. Newborn screening was added to the Recommended Uniform Screening Panel (RUSP) in 2016 and has been adopted in an increasing number of U.S. states. Newborn screening allows for monitoring before the potential onset of cerebral disease and therefore earlier treatment.

What are the treatments for cerebral ALD?

Hematopoietic stem cell transplantation (HSCT) has been the primary treatment strategy available to patients since the 1990’s. HSCT does not restore previous myelination or brain function, but has been shown to halt the progression of demyelination. Therefore, early detection of cerebral disease onset is critical to prevent damage to the brain occurring prior to treatment.

Pierpont, et al. (2018) Annals of Clinical and Translational Neurology

In this study, we sought to better characterize long-term outcomes in boys with cerebral ALD who underwent HSCT. Records from 137 boys who were treated with HSCT prior to 2016 were retrospectively reviewed. Among this patient group, 31 (23%) patients died within the year following HSCT. Among the surviving patients, there were 65 (61%) with information pertaining to their status at least one year after treatment. For these patients, we examined capacity for independent living skills such as communication, socialization, and self-care abilities. These skills are known as “adaptive functioning.”

Adaptive functioning was measured using the Vineland Adaptive Behavior Scale (VABS-ABC), which is a questionnaire for parents and caregivers to rate the patient’s ability to complete every day activities (e.g. “tells about experiences in simple sentences” or “uses toilet independently”). In the group of surviving patients, 22 (34%) were rated as having no impairment in adaptive functioning, 16 patients (25%) scored below average and 16 (42%) were severely impaired.

We studied which factors predicted whether a patient would have impairments in their adaptive functioning skills after treatment. The strongest predictor of patients’ post treatment outcomes was their score on a test of fine motor dexterity (the Purdue Pegboard) during appointments just prior to HSCT. The second most important predictor was their MRI severity score (the amount of disease visible on their brain scan) during that same pre-treatment time period. The figure below depicts the probability of having impairment on the adaptive functioning questionnaire after treatment (i.e., the color and shape of the data points) in relation to their scores on those pre-treatment predictors (i.e., their MRI scores and their scores on the fine motor test). The figure indicates that patients with less severe evidence of brain disease on their MRI and those with better fine motor functioning at the time of transplant had better ability to communicate, socialize and complete tasks independently in the years following their treatment.

From Pierpont, et al. (2018) Annals of Clinical Neurology.

Future directions

Increases in newborn screening implementation across the U.S. have led to earlier and detection and monitoring for cerebral disease among patients with ALD. While MRI results are a key factor in identifying cerebral disease, there is potential for functional assessments and screening tools such as those used in neurocognitive evaluations to improve monitoring of patients at risk for developing cerebral disease.