Secondary deficiency of neuraminidase 1 contributes to CNS pathology in neurological mucopolysaccharidoses via hypersialylation of brain glycoproteins.

Mucopolysaccharidoses (MPS) are lysosomal storage diseases caused by defects in catabolism of glycosaminoglycans. MPS I, II, III and VII are associated with lysosomal accumulation of heparan sulphate and manifest with neurological deterioration. Most of these neurological MPS currently lack effective treatments.

Human genetic defects of sphingolipid synthesis.

Sphingolipids are ubiquitous lipids, present in the membranes of all cell types, the stratum corneum and the circulating lipoproteins. Autosomal recessive as well as dominant diseases due to disturbed sphingolipid biosynthesis have been identified, including defects in the synthesis of ceramides, sphingomyelins and glycosphingolipids. In many instances, these gene variants result in the loss of catalytic function of the mutated enzymes.

Potential Role of Sphingolipidoses-Associated Lysosphingolipids in Cancer.

Sphingolipids play a key structural role in cellular membranes and/or act as signaling molecules. Inherited defects of their catabolism lead to lysosomal storage diseases called sphingolipidoses. Although progress has been made toward a better understanding of their pathophysiology, several issues still remain unsolved.

ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity.

In hepatocytes, peroxisome proliferator-activated receptor α (PPARα) orchestrates a genomic and metabolic response required for homeostasis during fasting. This includes the biosynthesis of ketone bodies and of fibroblast growth factor 21 (FGF21). Here we show that in the absence of adipose triglyceride lipase (ATGL) in adipocytes, ketone body and FGF21 production is impaired upon fasting.

Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target.

Objective: We evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans.

Design: Different models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice.

Are Glucosylceramide-Related Sphingolipids Involved in the Increased Risk for Cancer in Gaucher Disease Patients? Review and Hypotheses.

The roles of ceramide and its catabolites, i.e., sphingosine and sphingosine 1-phosphate, in the development of malignancies and the response to anticancer regimens have been extensively described.

First Report of a Patient with MPS Type VII, Due to Novel Mutations in , Who Underwent Enzyme Replacement and Then Hematopoietic Stem Cell Transplantation.

We report the case of a boy who was diagnosed with mucopolysaccharidosis (MPS) VII at two weeks of age. He harbored three missense β-glucuronidase ( variations in exon 3: two novel, c.422A>C and c.

Pregnancy outcome in Refsum disease: Affected fetuses and children born to an affected mother.

We describe the case of a young woman, from a consanguineous family, affected by adult Refsum disease (ARD, OMIM#266500). ARD is a rare peroxisomal autosomal recessive disease due to deficient alpha-oxidation of phytanic acid (PA), a branched-chain fatty acid. The accumulation of PA in organs is thought to be responsible for disease symptoms.

Inherited monogenic defects of ceramide metabolism: Molecular bases and diagnoses.

Ceramides are membrane lipids implicated in the regulation of numerous biological functions. Recent evidence suggests that specific subsets of molecular species of ceramide may play distinct physiological roles. The importance of this family of molecules in vertebrates is witnessed by the deleterious consequences of genetic alterations in ceramide metabolism.

Sweat chloride quantification using capillary electrophoresis.

Background: Cystic fibrosis (CF) is the less rare and severe genetic disease among the European population. Biochemical diagnosis of CF is based on the demonstration of increased chloride concentration in sweat samples, obtained during the sweat test (ST). WynSep developed a capillary electrophoresis with contactless conductivity detection (CE-C4D) able to measure sweat chloride with a low sample volume.

Monogenic neurological disorders of sphingolipid metabolism.

Sphingolipids comprise a wide variety of molecules containing a sphingoid long-chain base that can be N-acylated. These lipids are particularly abundant in the central nervous system, being membrane components of neurons as well as non-neuronal cells. Direct evidence that these brain lipids play critical functions in brain physiology is illustrated by the dramatic consequences of genetic disturbances of their metabolism.