Current research shows that rapid detection of Adrenoleukodystrophy can significantly reduce the rate of potential neurological damage in the life span of a male child who is genetically prone to acquiring the disease.
Adrenoleukodystrophy (ALD) is an X-linked genetic disorder that affects the adrenal gland and the nervous system in boys. In its most severe form, one of the manifestations of the disease is the deterioration of the brain of young males, leading to an early death. This deterioration is called Cerebral Adrenoleukodystrophy (cALD). cALD occurs in one-third of the boys diagnosed with ALD. The initial presentation begins with the inability to hold the boy’s attention due to sporadic impulsive decisions. Gradually, changes in behaviour and personality, visual impairment, auditory difficulties, and seizures follow.
Unfortunately, there has been no testing developed to detect which children diagnosed with ALD will get cALD, therefore making it difficult to produce measures for its prevention. The cerebral damage is usually detected by a radiology imaging technique called Magnetic Resonance Imaging (MRI) and the stage of severity is assessed using the Loes scoring system. The scoring system ranges from 0-35. A score of less than 0.5 is considered normal, and a score above 14 is considered severe. In children with cALD, hematopoietic stem cell transplant (HSCT) is the only known treatment that provides long-term survival. HSCT is the process of taking stem cells from a patient’s bone marrow, blood, or umbilical cord and infusing them into their veins. This is performed to boost a child’s immune system and help in the regeneration of damaged cells.
A study published in JAMA Neurology studied the neurocognitive outcomes of boys who had cALD with early cerebral damage and were treated with HSCT. The neurocognitive test primarily measured four domains – verbal comprehension, visual reasoning, working memory, and processing speed. In addition,, patients were assessed for sustained attention, the ability to remember unknown words, eye-hand coordination, and subtle movements (picking up and grasping objects). Following baseline MRI and neurocognitive testing, 139 patients with cALD received HSCT between January 1st, 1991 and October 20th, 2014 at the University of Minnesota.
Results of the study demonstrated that majority of study participants showed a decline in neurologic function after HSCT, even though they had an increased life span. However, the rate of decline varied between patients, depending on the baseline MRI severity score prior to undergoing the HSCT. If the research participant had a pre-HSCT MRI score of 2 or below, his post-HSCT score value declined at a much slower rate compared to a participant with a higher initial MRI score values. Participants who had higher baseline MRI score values (7 and above), the predicted 5-year scores declined in all test domains to scores around 39 score points. This decrease was visualized in later MRI scans that showed increased brain damage. Interestingly, in boys who had better pre-HSCT MRI scores, there was little to no decline seen in the predicted 5-year scores of test all domains. Preservation of neurological function was seen in patients who had better pre-HSCT MRI scores, illustrating the importance and need for the scientific community to work toward an early detection method for cALD.
Written By: Dr. Apollina Sharma, MBBS, GradDip EXMD