Ataxia, dysmetria and 6 month-history of progressive deterioration in school.
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Extensive confluent hypodense areas involving the periventricular and subcortical white matter, bilaterally in almost the entire cerebral hemispheres. There is some asymmetry with a more extensive appearance in the left frontal lobe.
Overall findings are suggestive of leukodystrophy versus progressive multifocal leukoencephalopathy.
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Extensive white matter abnormalities, in both cerebral hemispheres with prominence in the periventricular areas and asymmetric appearance (more in the left frontal lobe). In addition, severe involvement of the genu of the corpus callosum and extension through the capsules into both cerebral peduncles.
Geographic enhancement around the wither matter changes.
MR spectroscopy shows elevation of the choline peak, particularly at the deep parietal white matter and diffuse decrease of NAA peak. In general, findings are in keeping with active demyelination.
Overall, MR findings are consistent with multifocal/diffuse demyelination, similar to that in adrenoleukodystrophy.
This 10-year-old boy presented with ataxia, dysmetria and 6 month-history of progressive deterioration in school.
CT showed confluent hypodense white matter areas in both cerebral hemispheres, shown to be much more extensive in the subsequent MRI. This was diagnosed as X-ALD, but given the advanced damage, the patient would not benefit form bone marrow transplantation.
The detection of this case gave the raise to investigate his brother by assessing the very long-chain fatty acid levels (VLCFA), which is considered as a blood marker; the result was positive.
X-ALD is a metabolic condition associated with severe morbidity and mortality and characterized by damaged beta-oxidation of very long-chain fatty acids (VLCFA). This leads to an accumulation of VLCFA in plasma and tissues and causes a VLCFA mediated chronic toxicity, which can be in the form of progressive inflammatory demyelination.
The clinical manifestations differ widely between cerebral form, the adult form of adrenomyeloneuropathy (AMN) and Addison disease. The most common form is AMN, which is characterized by progressive peripheral neuropathy with onset usually in the 3rd and 4th decade.
Since it is X-linked disease, the female carriers are supposed to stay asymptomatic but over 80% of them develop AMN-like symptoms and peripheral neuropathy.
Generally, the morphological changes on MRI precede the clinical presentation, which points out the importance screening of family members. At the beginning of leukodystophy, a bone marrow transplant is known to stop the progression.
This case shows the importance of detecting X-ALD followed by extended family screening to capture the early manifestations of family members, who would benefit from bone marrow transplant.
Case contributed by Dr. Christine Saint-Martin, Associate Professor in the Neuroradiology and Pediatric Radiology at McGill University.
- Kemper AR, Brosco J, Comeau AM, et al. Newborn screening for X-linked adrenoleukodystrophy: evidence summary and advisory committee recommendation. Genet Med. 2017;19(1):121‐126. doi:10.1038/gim.2016.68
- Huffnagel IC, Dijkgraaf MGW, Janssens GE, et al. Disease progression in women with X-linked adrenoleukodystrophy is slow. Orphanet J Rare Dis. 2019;14(1):30. Published 2019 Feb 7. doi:10.1186/s13023-019-1008-6
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