The most common early signs associated with X-linked adrenoleukodystrophy (X-ALD) and concerns experienced by patients’ families were collected in a Japanese retrospective registry study. The findings may help in early disease diagnosis and the development of treatment strategies.
The study, “Characteristics of Japanese patients with X-linked adrenoleukodystrophy and concerns of their families from the 1st registry system,” was published in the journal Brain & Development.
Because of the implications of the genetic disorder on the central nervous system, the disease may include a wide range of neurological complications.
To date, only hematopoietic stem cell transplant (HSCT) — in which patients receive blood stem cells from their own system or a donor — has been effective for patients with X-ALD with neurological involvement. However, for optimal effect, the transplant approach should be taken in the early stages of the disease.
Because early symptoms are most often recognized by parents and others in proximity to the patient, better knowledge about early signs can result in better outcomes.
Therefore, to better understand initial disease symptoms and concerns raised by patients’ families, researchers in Japan created a registry system for X-ALD. This registry is part of the more extensive Japan Registration System for Metabolic & Inherited diseases (JaSMIn), established in 2013, and contains clinical data for more than 50 inherited metabolic disorders.
Researchers used a questionnaire — based on input from experts and family members of patients with X-ALD — to collect clinical information from patients, and allowed families to express possible concerns.
Of 45 forms sent, researchers received and analyzed 28 completed questionnaires from X-ALD patients (median age 14.5 years) and their families.
A first analysis of the answers showed that childhood cerebral form (78.6%) was the most common form of ALD among respondents.
The data also showed that the median age of X-ALD patients at symptom onset was 7.9 years. However, the median duration between onset of first symptoms and disease diagnosis was one year, and only half the patients were diagnosed within a year of symptom onset.
When analyzing onset signs, researchers found that the most common symptoms were behavioral or character changes (46.4%), walking problems (42.9%), strabismus (crossed or turned eyes; 39.3%), reduced academic ability (32.1%), and failing vision (21.4%).
These symptoms were most often recognized by family members (67.9%), followed by individuals in proximity to the patient, including teachers, friends, or the primary doctor (3.6% each).
At the time of enrollment in the registry, the most common symptoms experienced by patients were walking problems (78.6%), followed by functional and intellectual impairments, such as hearing, speech, and writing. Researchers also found that several of these symptoms worsened over time, confirming the progressive nature of X-ALD.
Analyses of the patients’ genetic profiles revealed that 64.3% had an established family history of X-ALD, and that 67.9% had confirmed mutations in the ABCD1 gene (the cause of X-ALD).
While half the patients received anti-epileptic drugs, 42.9% (12 patients) underwent HSCT. Of these 12, the families of two reported a noticeable improvement upon treatment based on magnetic resonance imaging (MRI) results.
Although the families of two other patients felt that the disease had been stabilized after HSCT, and five other patients had experienced deterioration of the condition, none of the families regretted the therapeutic approach.
Researchers also gathered disease-associated concerns raised by the patients and their families. The data showed that the most common concerns causing anxiety were associated with heredity issues (78.6%) and symptoms (57.1%). Frequent hospital visits (42.9%), problems at school/work (42.9%), economic issues (35.7%), and limited information regarding the disease (32.1%) were also causes of concern.
“This is the first study clarifying the clinical characteristics of X-ALD, and the concerns of patients’ families using the registry system,” the researchers said. “This registry system will help us to understand the clinical presentations of rare diseases such as X-ALD, and to identify unmet medical needs.”
According to the team, the “investigation of rare diseases using registry systems is very valuable for the understanding of such conditions.”