Posts Categorized: Part 12: LIPIDS

Triheptanoin and long chain fatty acid oxidation disorders

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Roe and Brunengraber recently reported outcomes in a large cohort of individuals with long chain fatty acid oxidation disorders (Molecular Genetics and Metabolism, 2015; 116(4):260-268). They compared therapy with MCT oil and low fat-high carbohydrate diet versus diet therapy+carnitine+trihepatanoin. The outcomes were quite striking: average frequency of serious clinical complications was approximately 60% with diet therapy alone […]

Phase 3 Trial in Lysosomal Acid Lipase Deficiency

Posted by & filed under Part 12: LIPIDS, Treatment.

  Lysosomal  acid lipase deficiency can cause cirrhosis and severe dyslipidemia. Burton et al. recently published in N Engl J Med a multicenter, randomized, double-blind, placebo-controlled study involving 66 patients with lysosomal acid lipase deficiency. This was a phase 3 clinical trial of enzyme-replacement therapy in children and adults, using sebelipase alfa. Sebelipase alfa was administered intravenously (1 […]

HMGCR is a genetic modifier for risk, age of onset and MCI conversion to Alzheimer’s disease

Posted by & filed under Part 12: LIPIDS, Part 28: NEUROGENETICS.

Leduc V et al. HMGCR is a genetic modifier for risk, age of onset and MCI conversion to Alzheimer’s disease in a three cohorts study. Mol Psychiatry. 2014 Jul 15 Leduc et al report a new genetic modulator of the risk for sporadic Alzheimer’s disease (AD) occurrence, as well as the risk of conversion from […]

A new model of the cardiomyopathy seen in Barth syndrome

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Wang et al (Nat Med. 2014 May 11. doi: 10.1038/nm.3545.) just published a fascinating set of experiences in which they created a model of a Barth Syndrome cardiac dysfunction by using “heart on chip” technology. This technology involves using Barth patient derived induced pluripotent stem cell derived cardiomyocytes seeded on micropatterned fibronectin rectangles in order to […]

Mutations in SERAC1 cause MEGDEL

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Wortman et al. (Nature Genetics, volume 44 (7), 797-802, 2012) recently published their discovery that mutations in SERAC1, a gene responsible for phosphatidylglycerol remodeling, are causative for MEGDEL (3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome) syndrome. This disorder shows striking similarities to another disorder of phospholipid remodeling with 3-methylglutaconic aciduria and prominent mitochondrial dysfunction: Barth […]

Heterogeneity of SCADD

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION, Part 12: LIPIDS.

JAMA. 2006 Aug 23;296(8):943-52. write my assignment Clinical, biochemical, and genetic heterogeneity in short-chain acyl-coenzyme A dehydrogenase deficiency. van Maldegem BT, Duran M, Wanders RJ, Niezen-Koning KE, Hogeveen M, Ijlst L, Waterham HR, Wijburg FA. This study of 31 patients from the Netherlands is the largest study of SCADD. It highlights the clinical heterogeneity, with […]

Gene therapy for SCAD

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Hum Gene Ther. 2006 Jan;17(1):71-80. Systemic correction of a fatty acid oxidation defect by intramuscular injection of a recombinant adeno-associated virus vector. Conlon TJ, Walter G, Owen R, Cossette T, Erger K, Gutierrez G, Goetzman E, Matern D, Vockley J, Flotte TR. In this article by a group from Pittsburg, proof of principle for gene […]

Bezafibrate for Sjögren-Larsson syndrome

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Sjögren-Larsson syndrome presents with ichtyosis, spastic diplegia and cognitive deficits. It is caused by a deficiency of fatty aldehyde dehydrogenase. Treatments are limited to symptomatic therapies; for example, ziluteon (an inhibitor of 5-lipoxygenase) can reduce pruritus. In a recent article, bezafibrate has been shown to induce the expression of the deficient protein in fibroblasts from […]

Diagnosing inborn errors of lipid metabolism with proton NMR spectroscopy

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In this publication, NMR is used to diagnose or follow patients with 4 different inborn errors of lipid metabolism: Smith-Lemli-Opitz syndrome Cerebrotendinous Xanthomatosis Sitosterolemia Refsum disease This technique might have a widespread clinical use in the future, given its advantages (authetic standards often unnecessary, almost unequivocal lipid identification, and easy sample preparation). Clin Chem. 2006 […]