Epidemiology and Natural History of Wolman and Cholesteryl Ester Stor (Grabowski)

University Of Minnesota, Minneapolis MN

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Abstract

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.