Adrenoleukodystrophy

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

Epidemiology

The estimated incidence is at around 1 : 20000-50000. 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 - ?
  • peripheral zone - ?
• 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 hyper intense
  • intermediate zone - iso to hypo intense
  • peripheral zone - moderately hypo intense

MR spectroscopy

May show evidence of neuronal loss manifested by a decease 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 very long chain fatty acids (VLCFAs) has also been trialled.

Differential diagnosis

Differential consideration for the classic pattern include:

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

Etymology

It is thought to be initially described by Siemerling and Creutzfeld in 1923¹.