Posts By: Hilary Vernon

Maternal affect on newborn biochemical markers

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It is well understood that transient elevations in specific acylcarnitine species on the newborn screen can actually originate from the infant’s mother. Often times this is thought to be due to an occult inborn error of metabolism, such as a mother with asymptomatic 3-methylcrotonyl-CoA carboxylase deficiency. However, I have often wondered how other clinical modifiers might contribute to false positive […]

SCAD deficiency: biochemical variant or clinically relevant IEM?

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

With the expansion of newborn screening in the past decade, biochemical variants are being uncovered without a clear understanding of their clinical significance. One such disorder is Short-chain acyl-CoA dehydrogenase (SCAD) deficiency, which causes an inability to process the shortest chain fatty acids. While early descriptions of this biochemical abnormality imply this is a disorder of […]


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Rhombencephalosynapsis is an abnormalty of the cerebellar midline including a missing vermis and fusion of the cerebellar hemispheres with or without other brain abnormalities. Ishak et al. (Brain 2012, Advance access March 26, 2012) offers a nice description of associated genetic syndromes and clinical features associated with this malformation.  Interestingly, this brain abnormality can be […]

Metabolite Proofreading?

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Van Schaftingen et al (JIMD, pub on line Jan 8, 2013) recently wrote a very interesting short review discussing several enzymes whose sole purpose appears to be to process aberrantly produced metabolites. These abnormal metabolites, such as L-2-hydroxyglutarate, are the product of substrate non-specificity of certain enzymes. This group proposes that defects in as of yet unknown “proofreading” enzymes could […]

Inborn errors of metabolism and metabolic networks

Posted by & filed under Part 03: GENERAL THEMES.

As information derived from large scale metabolomic investigations rapidly expands, organization of this data into relevant and interconnected pathways presents a very complex problem. Sahoo et al (Mol Biosyst. 2012 Oct;8(10):2545-58.) presented a very interesting approach to this problem, specifically in interconnecting missing reactions involved in fatty acid oxidation with existing models of the published human metabolic reconstruction. The resultant, […]

Mitochondrial Cardiomyopathy

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

Mitochondrial disease caused by mutations in mitochondrial DNA (mtDNA) can manifest in very different ways. If only an isolated organ is apparently affected, mtDNA defects might not be considered in the differential diagnosis. Giordano et al (Hum Pathol 2013 Jan 17) described three cases of isolated hypertrophic cardiomyopathy caused by homoplasmic mutations in the MTTI gene coding for mitochondrial isoleucine tRNA. […]

Vanishing White Matter Disease

Posted by & filed under Part 28: NEUROGENETICS.

I recently saw a very young patient in whom I made a diagnosis of Vanishing White Matter Disease (VWMD). This is a leukoencephalopathy caused by mutations in one of the subunits of eukaryotic initiation factor eIF2B, which plays an important role in regulation of protein synthesis in stress conditions. The family of this child wanted to know if […]

Chromosome 16p11 duplications

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I recently saw a child with autism, obsessive compulsive disorder, and anxiety, but who was non-dysmorphic and otherwise healthy. A karyotype from several years ago noted a euchromatic variant at chromosome 16p11, but a reinterpretation of this region has allowed us to diagnose this child with the chromosome 16p11 duplication syndrome. The 16p11.2-p12.2 duplication syndrome is associated […]

mtDNA mutation load in polar bodies vs. oocytes

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It is currently not possible to predict the outcome of children born to mothers who are carrying by delerious mtDNA mutations such as those causing MELAS and MERRF, due to the variable amounts of abnormal mtDNA that are passed to each offspring. cheap viagra super active This can make reproductive decisions very difficult for families. […]

2-Methylbutyryl-coenzyme A dehydrogenase deficiency

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Since the addition of the acylcarnitine profile to the newborn screen, debates about which conditions to include an exclude are becoming a very important issue. There are several “conditions” that are detected that are thought to be probably clin buy cialis online without a prescription ically insignificant. One of these “conditions” is 2-Methylbutyryl-coenzyme A dehydrogenase […]