Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (437 page)

   Assay of acid lipase activity in leukocytes, cultured fibroblasts, or cultured amniocytes

   Other Considerations

   Peripheral blood smear shows prominent vacuolation (in the nucleus and cytoplasm) of leukocytes. Abnormal liver function tests are caused by lipid accumulation.

   There is decreased adrenal cortical function with diffuse calcification on CT scan.

Suggested Readings

Anderson RA, Byrum RS, Coates PM, et al. Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease.
Proc Natl Acad Sci U S A.
1994;91:2718–2722.

Assmann G, Fredrickson DS. Acid lipase deficiency (Wolman’s disease and cholesteryl ester storage disease). In: Stanbury JB, Wyngaarden JB, Fredrickson DS, et al., eds.
Metabolic Basis of Inherited Disease
. 5th ed. New York: McGraw-Hill; 1983:803–819.

   
PEROXISOMAL DISORDERS

ADRENOLEUKODYSTROPHY (ALD)

MIM #300100

   Definition

Adrenoleukodystrophy is an X-linked disorder caused by mutation in the ABCD1 gene resulting in the defect of peroxisomal beta-oxidation and the accumulation of the saturated very long-chain fatty acids (VLCFA) in all tissues of the body. The manifestations of the disorder occur primarily in the adrenal cortex, the myelin of the central nervous system, and the Leydig cells of the testes. Even though men are largely affected with ALD, approximately 40% of X-ALD heterozygous females develop mild neurologic symptoms in their late 30s–40s.

   Relevant Tests and Diagnostic Value

Imaging studies:
MRI is always abnormal in males with neurologic symptoms caused by ALD

Very long-chain fatty acids (VLCFA) testing:

   Plasma concentration of VLCFA is abnormal in 99% of males; measurement of VLCFA is sufficient to establish the diagnosis in majority of man with ALD.

   Concentration of VLCFA is increased in plasma and/or cultured skin fibroblasts in approximately 85% of affected females.

Molecular genetic testing
—recommended when the measurement of VLCFA is inconclusive, for identification of familial mutation, and for prenatal testing when the familial mutation was established.

   Sequence analysis of the entire coding region

   Deletion/duplication analysis

Suggested Readings

Steinberg SJ, Moser AB, Raymond GV. X-linked adrenoleukodystrophy. In: Pagon RA, Adam MP, Bird TD, et al., eds.
GeneReviews
^™
[Internet]
. Seattle, WA: University of Washington, Seattle; 1999:1993–2013 [Updated 2012 Apr 19]. Available from:
http://www.ncbi.nlm.nih. gov/books/NBK1315