Lipid storage

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency has been recorded in only a few patients and these show wide variation in clinical presentation. The defect has been seen in infants with a syndrome of psychomotor retardation and failure to thrive. These infants showed abnormal organic aciduria, and drastically decreased SCAD activity was demonstrable in cultured fibroblasts. Muscle symptoms were only part of a wider syndrome in all infants and children so far reported to have SCAD deficiency, but were the sole presenting feature in two adult patients, in whom lipid storage was demonstrable in skeletal muscle. The gene encoding for human SCAD has been mapped to chromosome 12. 

H. Liedtke and G. Legler, in R. Salvayre, L. Douste-Blazy, and S. Gatt (Eds.), Lipid Storage Disorders, Plenum Press, New York, 1988, pp. 353-358. 

Fabry s disease An x-linked recessive lipid storage disease with an accumulation of the glycosphingolipid. 

The function of the ALD protein is not fully understood, and knockout mice lacking it do not exhibit the severe CNS neurological deficits commonly associated with the human disease despite a similar accumulation of VLCFAs [26], Furthermore, the clinical variability in human patients cannot be accounted for by the severity of the biochemical abnormality or the nature of the gene defect. These observations, plus other data from mice with defects in VLCFA metabolism, raise the issue of whether the accumulation of VLCFAs in myelin is crucial to the pathological mechanisms or is an epiphenomenon. Unlike most other lipid-storage diseases, active ALD brain lesions are characterized by perivascular accumulation of lymphocytes. For this reason, it has been hypothesized that the severity of CNS pathology may relate to an autoimmune reaction that varies from patient to patient and... 

Glutaric aciduria type II, which is a defect of P-oxida-tion, may affect muscle exclusively or in conjunction with other tissues. Glutaric aciduria type II, also termed multiple acyl-CoA dehydrogenase deficiency (Fig. 42-2), usually causes respiratory distress, hypoglycemia, hyperammonemia, systemic carnitine deficiency, nonketotic metabolic acidosis in the neonatal period and death within the first week. A few patients with onset in childhood or adult life showed lipid-storage myopathy, with weakness or premature fatigue [4]. Short-chain acyl-CoA deficiency (Fig. 42-2) was described in one woman with proximal limb weakness and exercise intolerance. Muscle biopsy showed marked accumulation of lipid droplets. Although... 

Hellerer, T., Axang, C., Brackmann, C., Hillertz, R, Pilon, M., and Enejder, A. 2007. Monitoring lipid storage in Caenorhabditis elegans using coherent anti-Stokes Raman scattering microscopy. Proc. Natl. Acad. Sci. USA 104 14658-63. 

Engel AG, Angelini C (1973) Carnitine deficiency of human skeletal muscle with associated lipid storage myopathy a new syndrome. Science 179 899-902... 

NPC1 257220 NPC1 protein F Complex (glyco-sphingo-)lipid storage disorder ... 

However, very low plasma levels of HDL cholesterol are also found in patients with genetically disturbed metabolic pathways that are indirectly linked to HDL metabolism. For example, many patients with lipid storage diseases like Gaucher s disease (glucocerobrosidase deficiency, OMIM 230800-231000), Nieman-Pick disease types A or (sphingomyelinase deficiency, OMIM 257200 and 607616, respectively), Niemann-Pick disease type C (OMIM 257220), hypertriglyceridemia, or diabetes mellitus present with low HDL cholesterol [22]. 

In another case, there was late-onset lipid storage myopathy, with secondary carnitine deficiency (SED-13, 150) (1187). 

Papadimitriou A, Servidei S. Late onset lipid storage myopathy due to multiple acyl CoA dehydrogenase deficiency triggered by valproate. Neuromuscul Disord 1991 l(4) 247-52. 

The metabolism of GSLs has been studied in cultured human fibroblasts from normal subjects, patients with lipid storage diseases, and those with FH. The content of the GSLs, as well as activities of the biosynthetic enzymes, the glycosyltransferases and the lysosomal GSL hydrolases,have been studied. Complex gangliosides, such as M1, GDla, have been found in this cell system to serve as receptors for cholera toxin and thyrotropin, respectively (24-26). More recently, GT1 and GDla have been postulated to be receptors for fibronectin in cultured fibroblasts... 

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