X-linked adrenoleukodystrophy

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Adrenoleukodystrophy (ALD) is a type of congenital dysmyelinating disease. It carries an X-linked inheritance.

Epidemiology

The estimated incidence is at around 1 : 20 000-50 000. Due to its X-linked inheritance it classically affects young males.

Pathology

The conditions results from an accumulation of very long chain fatty acids (VLCFAs) from a genetic deficiency in peroxisomal oxidation of fatty acids. This is thought to result from a mutation in a ALDP gene located on Xq28 ⁵. The cerebral white matter is typically split into three different zones:

central (inner) zone - irreversible gliosis and scarring
intermediate zone - active inflammation and breakdown of the blood-brain barrier
peripheral (outer) zone - leading edge of active demyelination

Phenotypes

There are five main phenotypes ³

childhood cerebral
adolescent cerebral
adult cerebral
AMN
limited to Addison's disease

Some individuals can be asymptomatic.

Radiographic features

MRI Brain

A majority of cases tend to show symmetrical cerebral white matter signal change involving the posterior periventricular white matter (i.e. posterior cerebral, around splenium and peritrigonal white matter). Signal changes can vary according to the zonal distribution within the affected white matter. There is relative sparing of sub-cortical u fiber involvement.

T1 -
- central zone - hypo-intense
- intermediate zone - content required
- peripheral zone - content required
T1 C+ (Gd)
- enhancement seen in ~ 50% of cases according to one study and is thought to be associated with disease progression ⁶
- with contrast infusion, serpiginous, garland-shaped enhancement may be visible in the anterior most periphery of the lesions ⁷
T2 :
- central zone - markedly hyperintense
- intermediate zone - iso- to hypo-intense
- peripheral zone - moderately hypo-intense

MR spectroscopy

May show evidence of neuronal loss manifested by a decrease in the NAA peak and an elevation in the lactate peak.

Treatment and prognosis

Bone marrow transplantation is thought to be favourable in the early stages of disease. Restriction of VLCFAs has also been trialled.

Differential diagnosis

Differential consideration for the classic pattern include:

acetyl CoA oxidase deficiency (pseudo a drenoleukodystrophy) - has a different clinical presentation

Etymology

It is thought to be initially described by Siemerling and Creutzfeld in 1923 ¹.

-</ul><h6>MR spectroscopy</h6><p>May show evidence of neuronal loss manifested by a decrease in the <a title="NAA" href="/articles/n-acetylaspartate-naa-peak">NAA peak</a> and an elevation in the <a title="Lactate peak" href="/articles/lactate-peak">lactate peak</a>.</p><h4>Treatment and prognosis</h4><p>Bone marrow transplantation is thought to be favourable in the early stages of disease. Restriction of VLCFAs has also been trialled.</p><h4>Differential diagnosis</h4><p>Differential consideration for the <strong>classic pattern</strong> include:</p><ul><li>
+</ul><h6>MR spectroscopy</h6><p>May show evidence of neuronal loss manifested by a decrease in the <a href="/articles/n-acetylaspartate-naa-peak">NAA peak</a> and an elevation in the <a href="/articles/lactate-peak">lactate peak</a>.</p><h4>Treatment and prognosis</h4><p>Bone marrow transplantation is thought to be favourable in the early stages of disease. Restriction of VLCFAs has also been trialled.</p><h4>Differential diagnosis</h4><p>Differential consideration for the <strong>classic pattern</strong> include:</p><ul><li>

References changed:

8. Engelen M, Kemp S, de Visser M et-al. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis. 2012;7 (1): 51. <a href="http://dx.doi.org/10.1186/1750-1172-7-51">doi:10.1186/1750-1172-7-51</a> - <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503704">Free text at pubmed</a> - <a href="http://www.ncbi.nlm.nih.gov/pubmed/22889154">Pubmed citation</a><span class="auto"></span>
9. Patel PJ, Kolawole TM, Malabarey TM et-al. Adrenoleukodystrophy: CT and MRI findings. Pediatr Radiol. 1995;25 (4): 256-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/7567229">Pubmed citation</a><span class="auto"></span>

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