Posts Categorized: Part 09: ORGANIC ACIDS



Organic acidurias: impact of age at onset and NBS

Posted by & filed under Newborn screening, Part 09: ORGANIC ACIDS.

The information of 567 patients with organic acidurias (OADs) from the E-IMD registry were analysed using recursive partitioning of diagnostic and therapeutic strategies, and odds ratios (OR) for health outcome parameters. Different OADs were included in this study: methylmalonic (MMA, n=164), propionic (PA, n=144), isovaleric (IVA, n=83), and type 1 glutaric aciduria (GA1, n=176). Of […]



Propofol use in methylmalonic acidemia

Posted by & filed under Part 09: ORGANIC ACIDS.

Our department’s general practice when advising on patients with organic acidemias who require surgery is to avoid the use of propofol. This practice was developed after a patient with methylmalonic acidemia (MMA) developed pancreatitis after a surgical procedure during which profofol was administered. However a recent review of the anesthesia administration in a cohort of 28 patients […]



ECHS1 deficiency and mitochondrial disease

Posted by & filed under New IEM, Part 09: ORGANIC ACIDS.

Haack et al (Annals of Clinical and Translational Neurology, 2015, 2 (5) pp. 492-509) recently reported a disorder of encephalopathy, deafness, optic atrophy, and cardiomyopathy caused by mutations in short-chain enoyl-CoA hydratase  (ECHS1). This mitochondrial matrix enzyme functions in the oxidation of fatty acids and some amino acids (particularly valine). Patients present with a wide range […]



IDH2 deficiency in mice: D2- hydroxyglutarate is neurotoxic and cardiotoxic

Posted by & filed under Part 09: ORGANIC ACIDS.

Specific gain of function mutations in IDH2 cause D2-hydroxyglutaric aciduria, a disorder with severe effects on the central nervous system including infantile encephalopathy, seizures, and white matter abnormalities. Cardiomyopathy is also an important feature of this disorder. Akbay et al. (Genes Dev. 2014 Mar 1;28(5):479-90. doi: 10.1101/gad.231233.113.) recently published a paper in which they described a conditional mouse […]



Positive newborn screens for C5OH

Posted by & filed under Newborn screening, Part 09: ORGANIC ACIDS.

There is much debate as to the clinical significance of 3-methylcrotonyl-CoA carboxylase deficiency (3MCC deficiency). In thinking about this issue, I recently read a paper by Arnold et al, (Mol Genet Metab. 2012 Aug;106(4):439-41)  that describes their retrospective analysis of 35 cases of 3-MCC deficiency identified by newborn screening and confirmed by enzyme and/or molecular analysis. One of the most […]



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 […]



Aberrant protein acylation is a common observation in inborn errors of acyl-CoA metabolism.

Posted by & filed under Part 09: ORGANIC ACIDS, _.

Pougovkina O et al. Aberrant protein acylation is a common observation in inborn errors of acyl-CoA metabolism. J Inherit Metab Dis. 2014 Feb 15. [Epub ahead of print]   An elegant study that formulates a new hypothesis for the role of aberrant acyl-CoA accumulation in disorders of acyl-CoA metabolism. Lysine acylation (in particular, acetylation) has […]



3-hydroxy-isobutyryl-CoA hydrolase deficiency causing deficiency of multiple mitochondrial respiratory chain enzymes and of the pyruvate dehydrogenase complex

Posted by & filed under Part 09: ORGANIC ACIDS, Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION, _.

Ferdinandusse S et al. HIBCH mutations can cause Leigh-like disease with combined deficiency of multiple mitochondrial respiratory chain enzymes and pyruvate dehydrogenase. Orphanet J Rare Dis. 2013 Dec 4;8:188.   Ferdinandusse et al describe two new patients (for a total of four patients described on the literature) with 3-hydroxy-isobutyryl-CoA hydrolase deficiency, a disorder of valine […]



X-linked Cobalamin Disorder

Posted by & filed under New IEM, Part 09: ORGANIC ACIDS.

Ye et al (AJHG (2013) 93, 506-514) described a new X-linked disorder of cobalamin processing caused by transcriptional dysregulation of MMACHC (cblC, combined methylmalonic acidema and homocysteinemia). This disorder is named cblX and is caused by mutations in HCFC1. HCFC1 is a global transcriptional regulator and in addition to the biochemical phenotype, these patients also have significant neurologic consequences […]



Propionic acidemia and hearing loss

Posted by & filed under Part 09: ORGANIC ACIDS.

An individual with Propionic Acidemia in his third decade of life who is cared for in our institution recently developed hearing loss. The patient’s mother  brought to our attention that on one of the family support group websites for Propionic Acidemia she noticed another affected adult wearing hearing aids. This was a complication I had not previously […]