Posts By: Hilary Vernon

Fresh Frozen plasma as a cholesterol source in Smith Lemli Opitz Syndrome

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Boctor and Wilkerson (Ann Clin Lab Sci. 2014 Summer;44(3):332-3., reported a case of Smith Lemli Opitz Syndrome in which low cholesterol levels were increased using fresh frozen plasma (FFP) in a situation where enteral replacement of cholesterol was not possible. To my knowledge, the practice of using FFP for cholesterol replacement in SLO has been employed previously as […]

SAM and SAH measurements in renal transplantation

Posted by & filed under Part 08: AMINO ACIDS.

Klepacki et al. (Clin Chim Acta. 2013 Jun 5;421:91-7. doi: 10.1016/j.cca.2013.03.003) developed reliable methodology to measure adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) levels via LC-MS/MS. The found SAH concentrations to be elevated in kidney transplant patients associated with acute rejection and nephrotoxicity events  compared to healthy controls and transplant patients without  transplant dysfunction. This brings up interesting questions about the role of metabolism […]

VARS2 and TARS2 mutations associated with mitochondrial disease

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

Increasingly, whole exome sequencing has been critical in resolving molecular causes of unknown metabolic or mitochondrial disorders. Diodato et al (Hum Mutat. 2014 Aug;35(8):983-9) used WES to identify homozygous mutations in VARS2 (Valyl tRNA synthetase)  in one patient seizures and deficiency mitochondrial respiratory chain complex I, and compound heterozygous mutations in TARS2 (threonyl-tRNA synthetase) in siblings with hypotonia, severe psychomotor delay and multiple […]

False positive newborn screens for C5

Posted by & filed under Part 09: ORGANIC ACIDS.

It can be very difficult to definitively rule out some inborn errors of metabolism once an infant has screened positive, and it is helpful to understand what circumstances may contribute to false positive results. An interesting situation was reported by Boemer et al (Mol Genet Metab. 2014 Jan;111(1):52-4.), in which a pivalate derivative was used in skin emollients provided […]

Valproic acid and hepatotoxicity

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

It is well known that in some individuals, administration of valproic acid leads to hepatotoxicity. The causes for this are not completely understood, though mutations in POLG are a well known risk factor. In a fibroblast model, Luis et al (JIMD, (2014) 37 353-357) found that Valproyl-CoA inhibited the activities of both GTP- and ATP-specific […]

Reduction of false positives in Newborn Screening

Posted by & filed under Part 03: GENERAL THEMES.

False positive newborn screening can represent a significant burden both emotionally and financially. Morris et al (Genetics in Medicine, 6(16), 2014) describes a protocol designed to reduce false positive screens in infants in a neonatal intensive care unit (NICU) setting. As part of this protocol,  total parenteral nutrition was replaced with dextrose/electrolyte fluid containing IV fluids for 3 h […]

Oxidative stress and X-linked ALD

Posted by & filed under Part 15: PEROXISOMES.

X-linked adrenoleukodystrophy (X-ALD), caused by a mutation in ABCD1, leads to an accumulation of long-chain fatty acids. However, the mechanism by which this accumulation causes disease is not yet understood.  One of the potential factors thought to contribute to disease is oxidative stress and subsequent free-radical damage. Petrillo et al (Molecular Genetics and Metabolism, 109 (4): 366–370) offers further evidence […]

A new model of the cardiomyopathy seen in Barth syndrome

Posted by & filed under Part 12: LIPIDS.

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 […]

MELAS and citrulline supplementation

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

Impaired nitric oxide production has been implicated in the pathogenesis of mitochondrial encephalomyopathy, lactic acidosis and stroke like episiodes (MELAS). Arginine supplementation is often employed as a precursor for nitric oxide and can have therapeutic effects in stroke-like episodes associated with MELAS. El-Hattab et al  (Mol Gen Metab 105 (2012) 607-614) reported that citrulline has an […]

mitochondrial tRNA synthetases

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

To date, nine nuclear encoded mitochondrial tRNA synthetases have been implicated in human disease, including DARS2 causing leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, HARS2 with Perrault Syndrome, and AARS2 causing fatal infantile cardiomyopathy. Recently, two groups have reported mutations in mitochondrial phenylalanyl–tRNAsynthetase (FARS2) leading to  infantile onset epilepsy, and a fatal Alpers-like encephalopathy […]