The history, physical, and symptoms of our patient resulted in the consideration of several possibilities as is evident by our differential diagnosis list. However, elevated concentrations of C24, C26, as well as abnormally high C24/C22 and C26/C22 ratios are indicative of hemizygosity for X-linked adrenoleukodystrophy; settling the diagnosis .
X-linked adrenoleukodystrophy (X-ALD) is an X-linked recessive disorder affecting approximately 1 in 21,000 males. This disease is caused by defective beta-oxidation of fatty acids in peroxisomes that leads to elevated serum concentrations of very-long-chain saturated fatty acids (VLCFA). The accumulation of cholesterol esters of the fatty acids and gangliosides in the membranes of cells in the brain, adrenal cortex, and other organs causes a primary adrenal insufficiency and progressive neurological dysfunction. The responsible gene, called ABCD1, is located on the long arm of the X chromosome (Xq28), and encodes a peroxisomal membrane protein, called ALDP (adrenoleukodystrophy protein), that belongs to the ABC super family of transporter proteins. Many mutations within ABCD1 have been detected.
There is considerable phenotypic variation among individuals affected with X-ALD. Broadly, cerebral adrenoleukodystrophy begins in childhood and includes behavior disturbances with rapid progression to dementia, blindness, and quadriparesis. Death typically occurs within months to several years of onset of symptoms. Adrenomyeloneuropthy is a milder and more slowly progressing form of X-ALD. It begins in adolescence or adulthood with symptoms of weakness, spasticity, and distal polyneuropathy and may include emotional lability, mania, or psychosis [2, 3]. Bladder dysfunction is a common manifestation of adrenomyeloneuropathy and can be a presenting symptom of this disease [4, 5].
Males carrying an X-ALD mutation will almost invariably develop disease, with about 50% developing adrenoleukodystrophy in early childhood and 50% developing adrenomyeloneuropathy later in adolescence or adulthood. Both phenotypes occur in the same family . Approximately half of heterozygous female carriers develop an AMN like syndrome .
The common concept of adrenoleukodystrophy involves images from the popular film Lorenzo's Oil, which was based on the true story of a young patient with the cerebral form of X-ALD. Although our patient had been specifically concerned about adrenoleukodystrophy, his efforts to be tested were always dismissed because he did not appear extremely ill. The adrenomyeloneuropathy phenotype is not well known, yet, our patient easily fits into its description. Victor, Ropper 2001 report, "We are caring for several adult men (with X-ALD) in whom the cerebral symptoms have been mild, allowing for high level cognitive function, the main manifestation consisting of personality quirks, spastic gait, urinary difficulty, testicular insufficiency, and baldness. Two of the men related the characteristic history of a male sibling who dies in childhood, ostensibly of Addison disease" .
X-ALD is estimated to be the cause of adrenal insufficiency in approximately 35% of patients with idiopathic Addison's disease and should be considered in the differential diagnosis of any male with adrenal insufficiency. Neurological symptoms, such as changes in gait or peripheral neuropathy, may appear before adrenal insufficiency . Patients may also present with psychiatric disturbances months to years before onset of other problems .