X-linked Adrenoleukodystrophy (X-ALD) is a rare inherited peroxisomal neurodegenerative disorder, chronically debilitating and life-threatening.

The disease is characterized by central inflammatory demyelination in the brain, axonal degeneration and adrenal insufficiency. Currently there is no satisfactory treatment.

The disease is caused by inactivation of the peroxisomal ABCD1 gene located on the X-chromosome. The defective function of the transporter leads to VLCFA accumulation in several tissues, including the white matter of the brain, the spinal cord and adrenal cortex.

ALD can present several forms depending on the severity of phenotype and the age of onset.

Childhood cerebral ALD (cALD) which is characterized by rapid cerebral demyelination with onset in the first decade of age (approx. 35% cases) evolving to dementia and death within few years.

Adrenomyeloneuropathy (AMN) which is the most common form of X-ALD (65% patients) develops the first signs at the age of 20-30 years. This form is progressively debilitating, affecting the spinal cord and peripheral nerve with spastic paraparesis. Life expectancy of AMN patients may be reduced when patients additionally develop cerebral demyelination and neuroinflammation, which is the case for about 20% of AMN patients. Female carriers (heterozygous) can also develop AMN like symptoms.

Addison-only: Primary adrenocortical insufficiency (Addison’s disease) without evidence for nervous system involvement occurs in 10% of ALD patients. However, in most patients neurological symptoms eventually occur.

The incidence of ALD is 1 of every 17.000 live births, including hemizygotes and heterozygous women who very often present with symptoms in adulthood.