Radiology Resident Case of the Week: January 26, 1996

Adrenal Leukodystrophy (ALD)

Mike Rubin, M.D.
Peer Review Status: Internally Peer Reviewed

Clinical Sx:
The disease usually presents in males age 5-10 years old with a gradual disturbance in gait and slight intellectual impairment. There is usually rapid progression with hypotension, seizures, visual complaints, and difficulty in swallowing appearing with time. Abnormal skin pigmentation or other signs and symptoms of adrenal insufficiency may become apparent before CNS symptoms. In some cases, adrenal symptoms never appear.

Etiology/Pathophysiology:
Classic ALD and the adult variant adrenomyeloneuropathy (AMN) are X-linked diseases in which there is deficiency of lignoceroyl-CoA ligase, a perioxisomal enxyme needed for the degradation of very long chain fatty acids (VLCFA).

Pathology:
White matter diseases are usually classified as demyelinating or dysmyelinating diseases. Dysmyelinating diseases such as ALD are inherited enzymatic deficiencies that cause abnormal formation or increased breakdown of myelin. Demyelinating diseases result in the loss of normally formed myelin by processes such as infection, chemotherapy, radiation, and autoimmune disorders such as multiple sclerosis.

The diagnosis of ALD is made by the assay of plasma, red cells, or cultured fibroblasts for increased amounts of VLCFA.

Miscellaneous:
The manipulation of diet using glyceryl trioleate-trieurucate oil (Lorenzo's oil) has been highly successful in lowering VLCFA, but not in affecting the rate of neurologic deterioration in symptomatic patients. Dietary pretreatment of neurologically asymptomatic patients may have some benefit. Currently, bone marrow transplant for patients who show early cerebral involvement is recommended. A drug therapy trial utililzing beta interferon and thalidomide is underway.

Adrenal Leukodystrophy can be subdivided into classic X-linked ALD and infantile ALD. Infantile ALD is included in the generalized perioxisomal disorders, which include Zellweger cerebro-hepato-renal syndrome and hyperpipeocloic acidemia. These disorders are associated with severe psychomotor retardation, dysmorphic facial features, hypotonia, seizures, and impaired liver functions. The severe abnormalities are present at birth and involve nearly every organ system.

Imaging:
The classic presentation on CT is low attenuation in the central occipital white matter that extends into the splenium of the corpus callosum. The edge of low attenuation may contrast enhance indicating the leading edge of inflammatory change. In the early phase of disease the peripheral white matter is spared. On MRI there is increased signal on T2 and decreased signal on T1 weighted images in the same distribution as described for CT.

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Key References:
1. Pediatric Neuroimaging. 2nd Edition. A. James Barkovich. Raven Press. 1995. pp58-63.
2. Mosher HW. Clinical and therapeutic aspects of adrenoleukodystrophy and adrenomyeloneuropathy. Journal of Neuropathology and Experimental Neurology. 1995; 54: 740-745.

Keywords:
Adrenal Leukodystrophy

Title Page

See related Provider Topics Brain and Nervous System, Genetics/Birth Defects or Leukodystrophies.

See related Patient Topics Brain and Nervous System or Genetics/Birth Defects.

All contents copyright © 1992-2004 the Author(s) and The University of Iowa. All rights reserved.

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