Posts Categorized: Part 16: LYSOSOMAL DISORDERS



Vitamin D and cardiomyopathy in Fabry disease

Posted by & filed under Part 16: LYSOSOMAL DISORDERS, _.

Drechsler C et al. Potential role of Vitamin D deficiency on Fabry cardiomyopathy. J Inherit Metab Dis. 2013 Oct 19. [Epub ahead of print] Vitamin D has been implicated in cardiac metabolism, although its exact role is still unclear. As Fabry patients are at risk for vitamin D deficiency due to a combination of sunlight […]



Gene therapy prevents severe outcomes of metachromatic leukodystrophy

Posted by & filed under Part 16: LYSOSOMAL DISORDERS.

The promising results of a gene therapy clinical trial for metachromatic leukodystrophy (MLD), an inherited lysosomal storage disease caused by arylsulfatase A (ARSA) deficiency, have bee recently published in Science. Three MLD patients in a presymptomatic stage were infused with hematopoietic stem cells genetically corrected with lentiviral vectors and showed extensive and stable ARSA gene replacement, which led […]



Yunis-Varón syndrome gene identification links this skeletal dysplasia with neurological involvement to phosphoinositide metabolism

Posted by & filed under Part 16: LYSOSOMAL DISORDERS, Part 22: CONNECTIVE TISSUE, Part 28: NEUROGENETICS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT.

Yunis-Varón syndrome is a skeletal dyplasia with features of cleidocranial dysplasia, with digital hypoplasia and severe neurological involvement (http://omim.org/entry/216340). Through exome sequencing, we identified three families with mutations of FIG4, encoding a phosphoinositide phosphatase. This enzyme had previously been implicated in Charcot-Marie-Tooth type 4J (CMT-4J). While CMT-4J is usually caused by a combination of a […]



Bioengineered sulphamidase for therapy of MPS IIIA

Posted by & filed under Part 16: LYSOSOMAL DISORDERS.

A paper recently published in EMBO Molecular Medicine by Sorrentino et al. showed efficacy of a chimeric sulphamidase that was engineered by adding the signal peptide from the highly secreted iduronate-2-sulphatase and the blood-brain barrier (BBB)-binding domain from the Apolipoprotein B. This bioengineered sulphamidase was highly secreted, was efficient in BBB transcytosis, restored enzyme activity in the brain, improved […]



Mutations in the nucleoside transporter gene SLC29A3 cause dysosteosclerosis, a form of osteopetrosis.

Posted by & filed under New IEM, Part 16: LYSOSOMAL DISORDERS, Part 22: CONNECTIVE TISSUE.

SLC29A3 is a lysosomal nucleoside transporter mutations in which cause histiocytosis–lymphadenopathy plus syndrome, a group of conditions with little or no skeletal involvement. We have now identified mutations in this gene in dysosteosclerosis, a form of osteopetrosis characterized by the additional features of platyspondyly, remarkable acquired metaphyseal osteosclerosis and red-violet macular atrophy of skin. We […]



Lysosomal Lysine/Arginine Transporter Identified

Posted by & filed under Part 08: AMINO ACIDS, Part 16: LYSOSOMAL DISORDERS.

In a forward genetic screen in C. elegans, Liu et al. identified LAAT-1, and its human counterpart PQLC2 as the lysosomal lysine/arginine transporter. Without this transporter, lysosomes become filled with arginine and lysine and this can cause cell death. Mutations in PQLC2 have not yet been identified in humans with lysosomal disorders. Liu B, Du […]



Proteostasis modulator for Niemann–Pick type C disease

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The paper by Yu et al. reports a strategy for modulating  cellular proteostasis and restore functional activity of NPC1 in primary fibroblasts of patients with Niemann–Pick type C disease. The authors of this paper found that ryanodine receptor (RyR) antagonists increased steady-state NPC1 levels in fibroblasts carrying the p.I1061T mutation, which is degraded by the proteasome. These compounds also […]



Intranasal ERT in LSDs may bypass BBB

Posted by & filed under Part 16: LYSOSOMAL DISORDERS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT, Treatment.

According to the study by Wolf et al. intranasal administration of α-l-iduronidase (IDUA) enzyme may be able to bypass the blood-brain barrier. This appears to be the case in IDUA-deficient mice after a single intranasal treatment with concentrated Aldurazyme®. Promising results in mice were also noted after intranasal treatment with an adeno-associated virus (AAV) vector expressing […]



Lysosomal Storage Disorders and calcium handling

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Several lysosomal storage disorders are characterized by aberrant calcium handling in affected cells (reviewed in Kiselyov et al, 2010, Cell Calcium 47:103-11). Increasing ER calcium stabilizes several lysosomal enzymes. It was shown that the chaperone calnexin significantly contributes to this phenomenon for glucocerebrosidase (Ong et al, 2010, Nat Chem Biol 6:424-32).   For more info […]



ERT for late-onset Pompe disease

Posted by & filed under Part 16: LYSOSOMAL DISORDERS, Part 25: MUSCLE.

van der Ploeg AT et al. A randomized study of alglucosidase alfa in late-onset Pompe’s disease. N Engl J Med. 2010 Apr 15;362(15):1396-406 In this study, alglucosidase alfa resulted in improved walking distance and stabilization of pulmonary function for patients with late-onset Pompe’s disease. posted by Philippe Campeau