Posts Categorized: _



Defects of the mitochondrial S-adenosylmethionine transporter cause intramitochondrial methylation deficiency

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

Mutations in SLC25A26, encoding the mitochondrial S-adenosylmethionine (SAM) transporter, were identified in patients in three families though homozygosity mapping and exome sequencing. Clinical manifestations ranged from foetal hydrops to episodes of lactic acidosis and cardiopulmonary collapse in childhood with chronic progressive muscle weakness. The authors showed that the defect of SAM import into mitochondria causes […]



Biotinidase deficiency should be considered in the differential diagnosis of myelopathy

Posted by & filed under Part 17: VITAMINS, _.

In this review, B. Wolf highlights the importance of considering biotinidase deficiency in the differential diagnosis of myelopathy. He reviews 18 previously reported patients who presented with spastic para- or tetraplegia due to myelopathy with and without vision loss and were ultimately diagnosed with profound biotinidase deficiency, but often after a prolonged diagnostic odyssey resulting […]



SS-31 and cardiolipin oxidative stress

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

We are increasingly aware of the role that oxidative stress plays in cellular pathophysiology. Cardiolipin, a phospholipid abundant in the inner mitochondrial  membrane, has been shown to be particularly susceptible to oxidative stress and peroxidation. This is particularly relevant due to the role that cardiolipin plays in cytochrome c activity. A recent antioxidant compound, SS-31 […]



zebrafish as a model for IEM research

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Wager et al. provide an interesting overview of how zebrafish can be used as a model for inborn errors of metabolism to understand their mechanistic basis. Available methods for creating and studying zebrafish disease models, advantages and disadvantages of using this model organism, novel mechanistic insights already provided using this model, and successful examples of […]



MSUD and BCKD expression

Posted by & filed under Part 08: AMINO ACIDS, _.

During a recent literature review on maple syrup urine disease, I came across an older article from 1998 (Suryawan et al. Am J Clin Nutr. 1998;68:72–81.) in which the authors examined branch chain amino acid metabolism (BCAT and BCKD) in various tissues. They found that most of the oxidative capacity was in skeletal muscle and liver (with muscle  representing the […]



Sir Archibald Garrod: A historical perspective

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I was recently reading the 1923 second edition of Sir Archibold Garrod’s seminal work entitled “Inborn Error of Metabolism” (Archibold E Garrod, “Inborn errors of metabolism” Oxford university press, London England 2nd edition, 1923) for a review article I am working on, and came across the following passage: “regards (to) the chemical composition of the tissues […]



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 […]



Genome sequencing and severe intellectual disability

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Severe intellectual disability occurs in 0.5% of newborns. Over the last years, using microarrays and exome sequencing has aided in the explanation of a big proportion of ID. Gilissen et al (2014) applied whole-genome sequencing to 50 patients with severe ID (whose extensive genetic work-up, including microarray and exome sequencing, was negative) and their unaffected parents. 84 de novo SNVs affecting the coding region were […]



Long-term effectiveness of enzyme replacement therapy in children with Gaucher disease

Posted by & filed under Part 16: LYSOSOMAL DISORDERS, _.

Anderson LJ et al. Long-term effectiveness of enzyme replacement therapy in children with Gaucher disease: results from the NCS-LSD cohort study. J Inherit Metab Dis. 2014 Mar 18. [Epub ahead of print] In a longitudinal prospective and retrospective cohort study, Anderson et al investigated the effectiveness of enzyme replacement therapy in children with Gaucher disease. […]



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 […]