A new case report describes two siblings with X-linked adrenoleukodystrophy (X-ALD) who had very different manifestations of the disease.
The study, “A Distinct Clinical Phenotype in Two Siblings with X-linked Adrenoleukodystrophy,” was published in the journal Neuro Endocrinology Letters.
X-ALD is caused by defects in the gene ABCD1 (ATP-Binding Cassette Subfamily D, Member 1). The lack of a functional version of this gene leads to a buildup of biological acids referred to as C24 and C26 (hexacosanoic and tetracosanoic acid, respectively), and increased levels of molecules called very long chain fatty acids (VLCFAs).
The first subject in the case report was a 6-year-old who was admitted to an endocrinology unit due to short stature. He was found to have abnormally high levels of adrenocorticotropic hormone, and low levels of the hormone cortisol, indicative of primary adrenal insufficiency (which can be a symptom of X-ALD). High levels of VLCFAs in the boy were also suggestive of X-ALD, though importantly, no genetic assessment was done.
At the time of admission, the patient’s brain magnetic resonance imaging (MRI) scan was normal, suggesting no brain involvement.
His primary adrenal insufficiency was managed for a while, but a year and a half after the initial diagnosis, the patient was admitted to the hospital with seizures, as well as hearing and vision problems. Imaging revealed a number of lesions in the patient’s brain; the boy’s condition rapidly deteriorated and he died soon thereafter.
The second patient in the case report was the 21-year-old brother of the first patient, who underwent genetic testing due to the history with the younger sibling. He was found to have a mutation that had previously been reported to cause X-ALD. He also had abnormally high levels of C26, also suggestive of X-ALD. Otherwise, the patient was healthy based on clinical examination.
These two contrasting disease presentations are particularly interesting because of the assumption that because the two siblings shared biological parents, they would have the same X-ALD-causing mutation — although it is important to stress that this was not confirmed in the study.
Still, researchers concluded that the “two male siblings with X-ALD due to a presumably identical, missense ABCD1 mutation and a distinct clinical phenotype, have shown the lack of phenotype-genotype correlation,” referring to a lack of correlation between the disease presentation (phenotype) and the patients’ genetics (genotype).
The team also emphasized that this case report “proved the essential role of molecular genetics analysis in early diagnosis.”