Carnitine uptake defect due to a 5′UTR mutation in a pedigree with false positives and false negatives on Newborn screening

We describe a family ascertained through 3 newborn screening (NBS) positive infants found to be unaffected themselves but in whom the mothers (sisters) were affected. There were also two affected children born to an affected male and his heterozygous wife who were false negatives on NBS but had increased fractional excretion of free carnitine in the urine. Analysis on a Next Generation Sequencing panel specifically designed to fully cover newborn screening disease targets showed a homozygous change in the five probands (SLC22A5; NM_003060:c.-149G > A; p.?). The mutation segregates with the CUD within the family. It is in the 5′ UTR and has a frequency within the gnomAd database of 0.001198. Plasma carnitine was decreased and fractional excretion of free carnitine was increased in all affected individuals. Functional carnitine uptake studies in cultured skin fibroblasts of one proband showed carnitine uptake at the 5 μM concentration to be 6% of controls. Relative expression of OCTN2 mRNA to beta-actin mRNA by qRT-PCR was increased in a proband relative to controls by a factor of 465-fold. Western blotting revealed a 120 kDa protein band, as well as a weaker 240 kDa band in the proband, the significance of which is unknown at this time.
Source: Molecular Genetics and Metabolism - Category: Genetics & Stem Cells Source Type: research

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Source: Pediatric Emergency Care - Category: Emergency Medicine Tags: Special Features Source Type: research
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Source: Cardiophile MD - Category: Cardiology Authors: Tags: HBC atrial infarction juvenile pattern Juvenile T inversion Loss of R wave progression Pardee’s sign pathological Q waves PR segment depression primary ventricular fibrillation ST segment abnormalities T wave abnormalities Source Type: blogs
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Source: World Journal of Cardiology - Category: Cardiology Authors: Tags: World J Cardiol Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Digestive Diseases and Sciences - Category: Gastroenterology Source Type: research
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Source: Rheumatology International - Category: Rheumatology Source Type: research
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Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
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Source: Dr. Smith's ECG Blog - Category: Cardiology Authors: Source Type: blogs
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Source: Dr. Smith's ECG Blog - Category: Cardiology Authors: Source Type: blogs
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Source: Journal of Cardiac Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: CASE REPORT Source Type: research
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