The proposed study is a multi-institutional historical chart review and longitudinal follow-up of identified patients with Wolman disease (WD) or Cholesteryl Ester Storage disease (CESD), lysosomal acid lipase deficiency (LAL). The overall goal of the proposed studies is to document and characterize the phenotypes, and their progression, as well as the determination of the genotypes of patients with lysosomal acid lipase (LAL;LPA locus) defects in the severe (WD) and attenuated (CESD) variants.
The specific aims are: 1. To characterize the degrees and progression of hepatic, splenic, intestinal, lung and adrenal involvement in CESD and WD using quantitative clinical assessments and to correlate these abnormalities with the genotype at the LPA locus. 2. To determine the variability of the phenotype in WD, a lethal infantile disease, and to quantify the rate of change of hepatic, splenic, intestinal malabsorptive and adrenal defects. These will be correlated with the genotype at the LPA locus. 3. Verify the impression that CSED and WD are non-CNS diseases and that CESD is significantly under diagnosed due to its marked variability with severely ill infants and nearly normal adults with """"""""fatty livers."""""""" Correlations with mutation, biopsy (e.g.,liver), and serum cholesterol and triglyceride levels will be developed as historical controls for future ERT trials.

Public Health Relevance

Wolman disease or Cholesteryl Ester Storage (CESD) disease patients will be studied to determine the natural history of liver, spleen, intestinal, lung and adrenal involvement, the relationship to their genotype, to verify that these diseases do not affect the central nervous system and to determine if CESD is underdiagnosed. This data will be essential for comparison for future enzyme replacement.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54NS065768-05
Application #
8545232
Study Section
Special Emphasis Panel (ZRG1-HOP-Y)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$78,540
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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