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New methodology for evaluating RC activity

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Goldenthal et al. (Mol Gen and Metab 105 (2012) 457-462) recently published a method for evaluating respiratory chain (RC) complex I and IV activity  and citrate synthase via a buccal swab sample. They report more than an 82% correlation between buccal sample and muscle tissue deficiencies.  The availability of this test adds to the arsenal of tools in […]



3-MCC deficiency

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The clinical significance of 3-MCC deficiency is a hotly debated topic, which rears it’s head in our own metabolism department every time a newborn screen is positive for this disorder. It is often difficult to describe the possible clinical consequences of this to new parents, and to provide guidelines for the short and long term follow […]



redundancy of the human genome

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Genome-sequencing studies indicate that all humans carry multiple genetic variants predicted to cause loss of function (LoF) of protein-coding genes. McArthur et al. estimated that human genomes contain ~100 genuine LoF variants with ~20 genes completely inactivated. They also described a method for using the differences found between LoF-tolerant and recessive disease genes to prioritize […]



Defects in PEX 11beta cause atypical peroxisomal disease

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Ebberink et al. in J Med Genet (2012 49(5):307-313) reported on a patient with an atypical presentation  for peroxisomal disease  including congenital cataracts, mild intellectual disability,  hearing loss, gastrointestinal problems, and recurrent migraines.  A peroxisomal disorder was pursued because of microscopic evidence for abnormal appearing peroxisomes in fibroblasts, even though all commonly tested biochemical studies were normal and […]



PSORS2 is Due to Mutations in CARD14

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Catherine Jordan et al are reporting in The American Journal of Human Genetics their study which “concludes a 17 year search for PSORS2”. PSORS2 is one of the loci identified in multiple GWAS and linkage studies as a risk locus for psoriasis and after sequencing of the genes in the identified chromosomal interval; ZNF750 was designated as […]



Pantothenate kinase-associated neurodegeneration

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Pantothenate kinase-associated neurodegeneration is an autosomal recessive disorder caused by mutations in PANK2, and is characterized by retinal degeneration and progressive loss of motor and cognitive skills. PANK2 encodes for pantothenate kinase localized to the mitochondria, and is the first enzyme required for de novo synthesis of CoA. A drosophila model of this disorder has been shown to […]



Pivalic acid and primary carnitine deficiency

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Rasmussen et al. (in J Inherit Metab Dis. 2012 May 8. Epub) recently published a series of patients with primary carnitine deficiency who had exposure to antibiotics containing pivalic acid and developed encephalopathy and lethal cardiac arrhythmia. Certian formulations of common antibiotics, such as ampicillin, contain pivalic acid in their prodrug form, and primary carnitine deficiency should be […]



Tyrosinemia and creatine kinase

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Tyrosinemia type 2 is an autosomal recessive disorder caused by mutations in the TAT gene (16q22.1) encoding tyrosine aminotransferase. Major clinical features include corneal lesions and hyperkeratotic skin plaques. In addition, there are well described neurological features including learning disabilities, tremor, ataxia and seizures. de Andrade et al. in Metab Brain Dis. 2011 Sep;26(3):221-7 offers in […]



2 methylbutyrylglycinuria

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I was asked to see a baby with a positive newborn screen with an elevation in C5 and mild elevation in C4 interpreted as being consistent with 2-methylbutyrylglycinuria. This  is not a disorder I am familiar with, and the literature is somewhat scarce. While the first few reported patients had features such as autism or mental retardation,  multiple […]



de novo mutations and autism

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Sanders et al. completed whole-exome sequencing in 238 families from the Simons Simplex Collection (SSC). SSC is a comprehensively phenotyped autism spectrum disorders cohort consisting of pedigrees with two unaffected parents, an affected proband, and, in 200 families, an unaffected sibling. Based on the results of whole-exome sequencing of a total of 928 individuals Sanders […]