X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by a defect in the ABCD1
(ATP-binding cassette, subfamiliy D (ALD), member 1) gene, located at Xq28. For clinical reasons, several distinct phenotypes have been characterised. There are four main categories which include adrenoleukodystrophy (X-ALD), adrenomyeloneuropathy (AMN), Addison only, and asymptomatic.1
gene encodes the ALD protein (ALDP) which serves as a half-sized peroxisomal transporter that undergoes dimerisation in order to shift very long chain fatty acids (VLCFA) into the peroxisome. Altered gene products of the ABCD1 protein may interfere with the transport of VLCFA into the peroxisome which in turn prevents VLCFA from β-oxidation and breakdown. Subsequently, VLCFA accumulate in the central nervous system, adrenal glands and testes.1,2
To date, more than 400 different mutations including missense (most prevalent), frameshift, insertion/deletion and splicing defects have been characterised (www.x-adl.nl
The recognition that no genotype–phenotype correlation could be identified led to the assumption that modifier genes exist. For example, the expression of BG1, a protein that activates VLCFA to VLCF-CoA, appears to correlate with the severity of the disease.4
The demyelinative process that is found in the cerebral hemispheres is the result of a vigorous inflammatory response which is characterised by dense infiltrates of perivascular CD8 cytotoxic T lymphocytes.5
Characterisation of the underlying pathology fostered the hypothesis that the autoimmune response represents a second hit that may be altered by therapeutic interventions such as haematopoietic stem cell transplantation.6
In addition to the inflammatory process described, a non-inflammatory distal axonopathy of the corticospinal tract is responsible for the progressive paraparesis in AMN.
The incidence has been estimated to be approximately 1:17000.7
As outlined in this case report, X-ALD may mimic common psychiatric disorders such as attention deficit/hyperactivity disorder. Furthermore, manifestations of ALD are often mistakenly attributed to other conditions such as multiple sclerosis or autoimmune adrenalitis.8
The diagnosis of X-ALD is commonly achieved by the demonstration of increased concentrations of VLCFA in the plasma. Additionally, genetic investigations are important to identify asymptomatic individuals.
This case report demonstrates that an increased level of awareness is essential when evaluating adolescents for symptoms of Addison’s disease or cognitive impairment. Apart from preventing overt adrenal crisis, early recognition is crucial since only boys presenting with mild symptoms represent potential candidates for bone marrow transplantation.9