Posts By: Hilary Vernon

New Syndrome of GNB5 Deficiency

Posted by & filed under New IEM.

Lodder et al (AJHG 2016 Aug 10 [epub ahead of print] just reported a new genetic syndrome caused by defects in the gene GNB5. Clinical features of this condition include: developmental delay,  hypotonia, gastroesophageal reflux, retinal abnormalities, seizures and cardiac sinus-node dysfunction. Clinical expression of this disease is variable, and there appears to be some genotype-phenotype […]

New disorder of mitochondrial tRNA processing

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

Metodiev and colleagues (AJHG, 98(5), p993–1000, 5 May 2016 ) recently reported a new mitochondrial disorder of mt-tRNA processing. Pathogenic variants were found in in TRMT10C in  2 unrelated probands via whole exome sequencing protein. Clinical features of the probands included neonatal lactic acidosis, hypotonia, feeding difficulties, deafness, and early death from respiratory failure. TRMT10C encodes  mitochondrial RNase P […]

mtDNA variants and LHON

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

While several different mtDNA variants are known to be associated with Leber’s hereditary optic neuropathy (LHON), penetrance is not 100%, and many of the factors contributing to increased penetrance have not been solved. One theory is that additive mitochondrial dysfunction caused by multiple LHON associated mtDNA variants could contribute to increased severity and/or penetrance of LHON. […]

Tools for IEM patients: Metabolic Diet App Suite

Posted by & filed under Part 03: GENERAL THEMES.

Ho et al (Molecular Genetics and Metabolism, 2016, 17: 322-327) introduced an online tool for both mobile devices and desktop computers that allows individuals with one of 15 different IEMs to plan and record meals based on individual recommendations. This app also has links to other line resources. The app is freely available at This […]

Adipose transplant for MSUD

Posted by & filed under Part 08: AMINO ACIDS.

In an article from a couple of years ago, Zimmerman et al (Mol Genet Metab. 2013 Aug;109(4):345-53) discuss evidence for improvement of biochemical measures with adipose transplant in 2 mouse models of maple syrup urine disease (MSUD). This brings up the very interesting question about which soft tissues provide adequate enzymatic activity for therapeutic replacement potential. […]

DNA methylation in mtDNA

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

I was recently reviewing evidence for epigenetic control in mitochondrial DNA and came across a nice review by Iacobazzi et al (Mol Gen Metab 2013, 110(2) 25-34). In this review, the authors describe evidence for methylation and other mechanisms for epigenetic control of mtDNA, and methodology for exploration of this. They also discuss evidence for this […]

Triheptanoin and long chain fatty acid oxidation disorders

Posted by & filed under Part 12: LIPIDS.

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 […]

A syndrome of Golgi Dysfunction

Posted by & filed under New IEM.

I am quite used to thinking of only the mitochondria in terms of Mendelian Disorders of organelle dysfunction, which is my own bias because of the majority of the patients I see. However, I was very interested to read a recent article published by Schmidt et al (AJHG (2015)97, 855-861) in which they describe an […]

A new gene for Optic Neuropathy

Posted by & filed under New IEM.

Optic neuropathy with or without other features is a common cause of referral to mitochondrial specialists, and can pose a diagnostic challenge. Whereas isolated optic neuropathies in and of themselves are devastating enough, those associated with broader mitochondrial diseases can herald a multi-organ progressive disorder. Angebault et al (AJHG 2015 (97) 754-760) described a new […]

Mutations in SLC25A26 and mitochondrial methylation defects

Posted by & filed under New IEM.

Kishita et al (AJHG 2015( 97) 761-768) just published a very interesting paper in which they describe that mutations in the mitochondrial S-adenosylmethionine (SAM) transporter SLC25A26 cause an autosomal recessive, severe mitochondrial disease. The mitochondrial functional defects are shown to be widespread and include RNA instability, translational defects, and cofactor biosynthetic defects. This leads one to wonder about […]