PDF | Lysosomal acid lipase deficiency (LALD) is an ultra-rare la presentación clínica: la forma infantil o enfermedad de Wolman y una forma. Palabras clave: Deficiencia de lipasa acida, enfermedad por depósito de esteres de colesterol, enfermedad de Wolman, dislipidemia, hepatomegalia bestthing.infoct %5Cnbestthing.info PDF download for Wolman Disease and Its Treatment, Article Information Enfermedad de Wolman en su forma aguda infantil. An Esp Pediat. ;
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Español (pdf) · Articulo en XML; Referencias del artículo; Como citar este artículo La enfermedad de Addison se caracteriza por una oferta insuficiente de .. -- Enfermedad de Wolman: es la asociación de insuficiencia. A collection of disease information resources and questions answered by our Genetic and Rare Diseases Information Specialists for Wolman disease. The novel c+2T>G mutation accounted for 75% of the Wolman .. The CIBER of Enfermedades Raras (CIBERER) is an initiative of the.
Regarding the clinical point of view, patients presenting this mutation in homozygosity did not show any differential trait compared with the other WD patients with other mutations.
The second frequent WD associated c. This mutation is known to result not only in a major non-functional transcript with the skipping of exon 8, causing the deletion of 24 amino acids p.
The Change c. As the mutation p. QH is predicted to be damaging by the mutation effect predictors, its presence would cause the loss of the activity of the protein translated from the correctly spliced mRNA.
The presumably lack of activity correlates with the fact that we identified the c. The other mutation detected in a WD patient of our cohort was c. It was detected in homozygosity in one WD patient but also in compound heterozygosity with the common c.
These findings agree with the literature, as this mutation was previously described in homozygosity in one WD case Sadhukhan et al. One CESD patient showed the reported p. HR mutation in homozygosity and three patients carried the same mutation in heterozygosity, giving the idea that this change is associated with some residual activity and being associated with a milder phenotype Ries et al.
Regarding the other mutations detected in heterozygosity in CESD patients of our cohort p.
H86Y, p. Ddel and c.
We observed that both the two common mutations in our series c. This observation strongly supports the hypothesis of a common ancestor for this mutation suggested by Fasano et al.
Regarding the novel c. For the other mutations identified in more than one allele, as they co-segregates with different haplotypes, it is to be assumed that they are recurrent mutations affecting hot spots in LIPA gene.
In conclusion, we identified four novel and four previously described mutations in a cohort of 23 Spanish LAL deficiency patients. The majority of the CESD patients carried the common mutant allele c. These two mutations co-segregated with a unique haplotype suggesting a presence of a common ancestor. Our study contributes to the LAL deficiency acknowledgement with novel mutations and with high frequencies of some unknown mutations for WD.
Acknowledgments The authors declare no conflict of interest. The authors want to thank all the physicians who referred the samples of the patients. The authors also thank Dr.
Jarque for excellent technical assistance. Central de Asturias , Mateos, Merino H. Non-contrasted computed axial tomography evaluates liver attenuation measured in Hounsfield units and attenuation values between the liver-spleen.
Magnetic resonance and elastography optimization are also diagnostic methods, as is nuclear magnetic resonance spectroscopy. Figure 4.
Non-contrasted computed tomography scan with Hounsfield unit measurement in the liver and spleen. A cholesterol moiety has five CH3 groups with a strong resonance on the 1H magnetic resonance spectrum compared with a fatty acid moiety that has one methyl group per molecule. Pathology The histopathologic study of biopsies from patients with LAL-D offers at least three benefits: a on its own, it can be indicative of the disease, b it contributes to confirming diagnosis when the disease is suspected, and c it provides valuable information for establishing outcome and is useful in patient follow-up, treatment evaluation, and for a retrospective analysis.
Guía colombiana para el diagnóstico de la deficiencia de lipasa ácida
The liver and all organs with a predominance of macrophages are the most commonly affected. The cytoplasm of the hepatocytes contains numerous lipid droplets that are intensely positive with the oil red O stain.
Those vesicles measure less than one micron in diameter and do not displace the nucleus fig. C Semi-fine slices that show the microvesicular nature of the steatosis, seen in practically all the hepatocytes toluidine blue, original magnification x D Multiple neutral fat droplets are revealed in the entire hepatic lobule oleous red, original magnification x Diffuse microvesicular steatosis and cholesterol crystals in the cytoplasm of hepatocytes and macrophages are liver biopsy findings suggestive of LAL-D.
The monocyte-macrophage system lesion affects Kupffer cells and the portal macrophages. Both show small droplets and cholesterol crystals in their cytoplasm.
In addition, macrophages accumulate pigment similar to lipofuscin fig. B Silver birefringence characteristic of the numerous cholesterol crystals polarized light, original magnification x C Kupffer cells with microvesicular steatosis and cholesterol crystals clearly stand out PAS, original magnification x1, Two basic tools demonstrate the existence of lipids inside lysosomes: immunohistochemistry and electron microscopy.
Antibodies can be used that recognize lysosomal components, such as lysosomal integral membrane protein-2 LIMP2 , a protein associated with lysosome associated membrane protein-1 LAMP1 , and the lysosomal luminal protein or cathepsin D fig.
Figure 7. A Immunohistochemical reaction showing lipid droplets inside lysosomes cathepsin D, original magnification x B Photomicrograph showing lipids surrounded by simple lysosomal membrane that reveals its lysosomal nature, as well as cholesterol crystals electron microscopy, original magnification x2, Through electron microscopy, lipids are viewed inside the lysosomes fig.
Liver fibrosis is dependent on progression time and disease expressivity, which can range from mild disease to cirrhosis. Late-presentation LAL-D should be ruled out in non-obese adult patients with cryptogenic cirrhosis of the liver. It is useful for detecting affected patients 2 and its sensitivity and specificity is very high.
The blood is absorbed and left to dry at room temperature until the following day. The sample should not be exposed to heat and should be transported in double bags with desiccant, to maintain enzyme activity. An international expert consensus for LAL diagnosis determined the importance of analyzing LAL activity results based on the percentage of activity, with respect to the normal mean of the healthy reference population analyzed by each laboratory.
Enzymatic diagnosis of LAL-D can be made through the dried blood spot test on filter paper. It is located at 10q The test is carried out in peripheral blood leukocytes and involves the sequencing of the LIPA gene or of a gene panel containing it. DNA is extracted from the sample leukocytes or DBS for sequencing the gene or for massive sequencing.
In Mexico, the c.
Molecular diagnosis should be considered as a support method, given that the mutation s responsible cannot always be identified, as well as its high cost.Linari S, Castaman G. Deficient activity of hepatic acid lipase in cholesterol ester storage disease. Oelkers W. Generalized xanthomatosis with calcified adrenals.
HR mutation in homozygosity and three patients carried the same mutation in heterozygosity, giving the idea that this change is associated with some residual activity and being associated with a milder phenotype Ries et al.