Magnetic resonance spectroscopy

X-linked adrenoleukodystrophy (ALD) has two distinct neurologic phenotypes: the slowly progressive adrenomyeloneuropathy (AMN) and the rapidly progressive inflammatory cerebral phenotypes (CERALD).¹ The main pathologic abnormality in AMN is a non-inflammatory distal axonopathy that affects the long tracts in the spinal cord most severely.² A recent spectroscopy study demonstrated evidence of axonal pathology in the brain of pure AMN patients.³ In CERALD there is an inflammatory cerebral myelopathy associated with intense perivascular cuffing by cells, most of which are CD8 cytotoxic T-cells. The CD1 mediated presentation of lipid antigens that contain the saturated very long chain fatty acids that are characteristic of ALD may be a key pathogenetic element.⁴ More than 400 different mutations in ABCD1, the gene that is deficient in ALD, have been identified. They do not correlate with the neurologic phenotype.¹ AMN and CERALD often co-occur in the same family. The inability to predict whether a young asymptomatic boy with ALD is at risk for AMN or for CERALD is one of the most serious gaps in knowledge about ALD.

While there is as yet no consistently effective therapy for AMN, hematopoietic stem cell transplantation (HSCT) can benefit patients with CERALD. This is documented in the recent study by Peters et al. …