|
Wolman Disease
|
1.000 |
CausalMutation
|
disease |
CLINVAR |
Wolman disease (LIPA p.G87V) genotype frequency in people of Iranian-Jewish ancestry.
|
21291321 |
2011 |
|
Wolman Disease
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
With the recent introduction of enzyme replacement therapy to manage LAL deficiency comes the need for a reliable assay of LAL enzymatic activity that can be applied to dried blood spots (DBS).
|
29339442 |
2018 |
|
Wolman Disease
|
1.000 |
Biomarker
|
disease |
BEFREE |
We provide evidence that the strikingly more severe course of Wolman disease is caused by genetic defects of LAL that leave no residual enzyme activity.
|
8617513 |
1996 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We identified two LALD patients (one homozygous and one compound heterozygous) and one carrier of a novel LIPA variant.
|
31004967 |
2019 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We conclude that in two siblings with a novel LAL variant and mild phenotype of CESD, lovastatin decreased both serum lipid concentrations and hepatocellular lysosomal content.
|
9365051 |
1997 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
CLINVAR |
Unfavorable outcome of hematopoietic stem cell transplantation in two siblings with Wolman disease due to graft failure and hepatic complications.
|
23583223 |
2013 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
To estimate the prevalence of CESD in different populations, the frequencies of the c.894G>A mutation were determined in 10,000 LIPA alleles from healthy African-American, Asian, Caucasian, Hispanic, and Ashkenazi Jewish individuals from the greater New York metropolitan area and 6,578 LIPA alleles from African-American, Caucasian, and Hispanic subjects enrolled in the Dallas Heart Study.
|
23424026 |
2013 |
|
Wolman Disease
|
1.000 |
Biomarker
|
disease |
BEFREE |
Thus, this similar deficiency demonstrates that, in lymphoid cell lines, triolein and cholesteryl esters are hydrolysed (under the conditions used here) by a single enzyme, i.e., lysosomal acid lipase muted in Wolman's disease.
|
6329310 |
1984 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
This study provides additional data on the features of childhood-onset LAL-D and describes two novel pathogenic variants of the LIPA gene.
|
28881270 |
2017 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
This is the first description of two different, naturally occurring mutations involving the same amino acid residue in the lysosomal acid lipase in unrelated CESD patients.
|
9633819 |
1998 |
|
Wolman Disease
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
These studies provide feasibility for LAL enzyme therapy in human WD and CESD.
|
11487567 |
2001 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
These preliminary anecdotal findings in a CESD patient with novel LIPA mutations support the longer term safety of statins in an adolescent patient and provide new data about the potential efficacy and tolerability of ezetimibe in this patient group.
|
16255772 |
2005 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
These include Wolman disease (WD) and Cholesteryl Ester Storage Disease (CESD) which both result from mutations in LIPA, the gene that encodes lysosomal acid lipase (LAL).
|
29246491 |
2018 |
|
Wolman Disease
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
These data demonstrate high-level lysosomal expression of recombinant LAL in vitro and in vivo and show the feasibility of gene therapeutic strategies for the treatment of Wolman disease.
|
11177564 |
2001 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Then, we examined the structural changes in the LAL protein caused by the WD/CESD mutations, using molecular modeling software TINKER.
|
22138108 |
2012 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The reduction of LAL activity in nine heterozygote, disease free carriers of mutations from two cholesteryl ester storage disease (CESD) pedigrees and the family of a patient with Wolman disease was associated with an increased fraction of monocytes which expressed CD56 (N-CAM) (4.1 +/- 2.7% of monocytes, compared to 2.2 +/- 0.5% in ten controls, P < 0.05), an antigen characteristic of immature myeloid cells, suggesting an increased turnover of monocytes.
|
9126667 |
1997 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The novel synonymous variant in LIPA gene affects splicing and causes lysosomal acid lipase deficiency.
|
31230978 |
2019 |
|
Wolman Disease
|
1.000 |
Biomarker
|
disease |
BEFREE |
The essential role of LAL in lipid metabolism has been confirmed in human and mice with LAL deficiency.
|
29547398 |
2018 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The dosage of serum lysosomal acid lipase was undetectable and we found the presence of a rare homozygous mutation in the gene associated with the lysosomal acid lipase deficiency, (allele c.386A > G homozygous p.H129R).
|
31113597 |
2020 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The complete absence of the lysosomal acid lipase (LAL) enzyme function causes Wolman's Disease that is fatal within the first six months of life.
|
22795295 |
2013 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The commonest genetic cause of cholesteryl ester storage disease is an exon 8 splice junction variant in the LIPA gene (rs116928232, c.894G>A; E8SJM) previously found to have an allele frequency of 0.0011 (1 in 450 individuals) in a large European population.
|
30056760 |
2019 |
|
Wolman Disease
|
1.000 |
Biomarker
|
disease |
MGD |
Targeted disruption of the mouse lysosomal acid lipase gene: long-term survival with massive cholesteryl ester and triglyceride storage.
|
9700186 |
1998 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
CLINVAR |
Structural bases of Wolman disease and cholesteryl ester storage disease.
|
22138108 |
2012 |
|
Wolman Disease
|
1.000 |
Biomarker
|
disease |
BEFREE |
Since the severely reduced LAL activity was seen in cells from an adult patient with a mild CESD, we conclude that there is no simple direct correlation between the LAL molecular lesions and the biochemical and clinical phenotypes.
|
9367797 |
1997 |
|
Wolman Disease
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Since the residual LAL activity is higher and the clinical phenotype based on plasma lipid values and severity of hepatosplenomegaly is milder in this case than in a previously studied case who was homozygous for the E8SJM allele, we conclude that the L336P variant appears to be associated with a phenotypically mild form of CESD.
|
7773732 |
1995 |