Diagnosis:
Very long chain fatty acids VLCFAs: raised C26:0 level, raised C26:0/C22:0 ratio, raised C24:0/C20:0 ratio. This is diagnostic. Genetic tests usually follow.
A type of peroxysomal disease. A type of leukodystrophy a.k.a. dysmyelination
Genetics:
X-linked or Autosomal recessive (neonatal)
ALD gene a.k.a. X-linked adrenoleukodystrophy gene chr. Xq28, encoding perioxysomal ATP binding cassette half-transporter protein ABCD1.
Very long chain fatty acids VLCFAs: raised C26:0 level, raised C26:0/C22:0 ratio, raised C24:0/C20:0 ratio. This is diagnostic. Genetic tests usually follow.
Acyl-CoA synthetase deficiency
Findings on investigations:
MRI:
- Affects white matter in brain and spinal cord. Advances from posterior to anterior or anterior to posterior. Frontal, parietal, occipital, temporal lobes, corpus callosum. Spares U (arcuate) fibres.
- Trigonal or frontal calcification may occur
- T2: hyperintense
- Enhancement of advancing edge or major white matter tracts indicates disease activity.
Endocrine:
- Adrenal insufficiency: low cortisol, high ACTH
- Primary Hypogonadism
Electrophysiology/NCS:
- Peripheral neuropathy, demyelinating
CSF: raised protein
Pathology:
Symmetric pathology in white matter
Demyelination i.e. myelin loss (Luxol fast blue LFB stain), lipid laden macrophages (PAS positive). Secondary changes in the spinal cord.
In chronic lesions: central cavitation, central astrocytic gliosis. Peripheral macrophages. Perivascular lymphocytes mainly T cells CD8. Cytoplasmic inclusions in macrophages (lamellar on EM)
Adrenals: cytoplasmic inclusions in cells in zona fasciculata-reticularis
Testes: cytoplasmic inclusions in interstitial cells
Treatment:
If early in the disease consider allogeneic hematopoietic stem-cell transplantation.
Promising therapies: Lenti-D gene therapy (autologous CD34+ cells transfected with a lentiviral vector that contains ABCD1 complementary DNA).
Related articles:
References:
- Aubourg P, Blanche S, Jambaqué I, et al. Reversal of early neurologic and neuroradiologic manifestations of X-linked adrenoleukodystrophy by bone marrow transplantation. N Engl J Med 1990;322:1860-1866.
- Eichler F, Duncan C, Musolino PL, et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N Engl J Med 2017;377:1630-1638
- Loes DJ, Hite S, Moser H, et al. Adrenoleukodystrophy: a scoring method for brain MR observations. AJNR Am J Neuroradiol 1994;15:1761-1766.