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.
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.
|Mauer, Michael; Glynn, Emily; Svarstad, Einar et al. (2014) Mosaicism of podocyte involvement is related to podocyte injury in females with Fabry disease. PLoS One 9:e112188|
|Rumsey, Robin K; Rudser, Kyle; Delaney, Kathleen et al. (2014) Acquired autistic behaviors in children with mucopolysaccharidosis type IIIA. J Pediatr 164:1147-1151.e1|
|Schiffmann, Raphael; Forni, Sabrina; Swift, Caren et al. (2014) Risk of death in heart disease is associated with elevated urinary globotriaosylceramide. J Am Heart Assoc 3:e000394|
|Polgreen, Lynda E; Thomas, William; Fung, Ellen et al. (2014) Low bone mineral content and challenges in interpretation of dual-energy X-ray absorptiometry in children with mucopolysaccharidosis types I, II, and VI. J Clin Densitom 17:200-6|
|Polgreen, Lynda E; Thomas, William; Orchard, Paul J et al. (2014) Effect of recombinant human growth hormone on changes in height, bone mineral density, and body composition over 1-2 years in children with Hurler or Hunter syndrome. Mol Genet Metab 111:101-6|
|Stevenson, David A; Rudser, Kyle; Kunin-Batson, Alicia et al. (2014) Biomarkers of bone remodeling in children with mucopolysaccharidosis types I, II, and VI. J Pediatr Rehabil Med 7:159-65|
|Prater, Sean N; Banugaria, Suhrad G; Morgan, Claire et al. (2014) Letter to the Editors: Concerning "CRIM-negative Pompe disease patients with satisfactory clinical outcomes on enzyme replacement therapy" by Al Khallaf et al. J Inherit Metab Dis 37:141-3|
|Schiffmann, Raphael; Mayfield, Joan; Swift, Caren et al. (2014) Quantitative neuroimaging in mucolipidosis type IV. Mol Genet Metab 111:147-51|
|Wang, Raymond Y; Braunlin, Elizabeth A; Rudser, Kyle D et al. (2014) Carotid intima-media thickness is increased in patients with treated mucopolysaccharidosis types I and II, and correlates with arterial stiffness. Mol Genet Metab 111:128-32|
|Ahmed, Alia; Whitley, Chester B; Cooksley, Renee et al. (2014) Neurocognitive and neuropsychiatric phenotypes associated with the mutation L238Q of the *-L-iduronidase gene in Hurler-Scheie syndrome. Mol Genet Metab 111:123-7|
Showing the most recent 10 out of 34 publications