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

Related Links:

We present 4 patients along with their emergency department course, so providers will have a better understanding of the identification and workup of these patients. Currently, it is unclear when this inflammatory syndrome develops in respect to a COVID-19 infection. The clinical features of this syndrome seem to overlap between Kawasaki disease, toxic shock syndrome, and myocarditis. All patients presenting to our emergency department had fever, variable rash, abdominal pain, vomiting, and/or diarrhea. Patients remained persistently tachycardic and febrile despite being given proper doses of antipyretics. Severity of pres...
Source: Pediatric Emergency Care - Category: Emergency Medicine Tags: Special Features Source Type: research
ECG changes in coronary artery disease (CAD) can be in any of the waves or segments. Diagnosis of acute myocardial infarction in the emergency room still relies mostly on the ECG, though other investigations are there to supplement. P wave abnormalities P wave being an atrial event, is not usually involved directly by CAD. But indirectly, there can be evidence of atrial enlargement if there is left ventricular dysfunction. Atrial arrhythmias are observed in atrial infarction. Abnormalities of PR segment PR segment contains the atrial repolarization wave (Ta) though it is not usually evident. PR segment depression can occu...
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
CONCLUSION: This case highlights a unique etiology of acute myocardial infarction in a patient with SAH leading to ST elevations, diffuse triple vessel CAV and apical scar. PMID: 33014294 [PubMed]
Source: World Journal of Cardiology - Category: Cardiology Authors: Tags: World J Cardiol Source Type: research
Matrine (MT) is a naturally occurring alkaloid and an bioactive component of Chinese herbs, such as Sophora flavescens and Radix Sophorae tonkinensis. Emerging evidence suggests that MT possesses anti-cancer, anti-inflammatory, anti-oxidant, antiviral, antimicrobial, anti-fibrotic, anti-allergic, antinociceptive, hepatoprotective, cardioprotective, and neuroprotective properties. These pharmacological properties form the foundation for its application in the treatment of various diseases, such as multiple types of cancers, hepatitis, skin diseases, allergic asthma, diabetic cardiomyopathy, pain, Alzheimer’s disease (...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
DiscussionMMF is well known for common GI side-effects such as nausea, diarrhea, vomiting, ulcers, abdominal pain and rarely gastrointestinal bleeding. Few studies reported 3 to 8% incidence of ulcer perforation and GI bleeding within 6 months. Risk of gastroduodenal erosions is nearly 1.83 times for MMF, with the highest lesions associated with MMF-tacrolimus-corticosteroid combination treatment as seen in our patient. Hypothesis is that GI tract is vulnerable because of dependence of enterocytes on de novo synthesis of purines, which is disrupted by MMF. Typically, upper GI mucosal injuries of mucosal irritation leading ...
Source: Digestive Diseases and Sciences - Category: Gastroenterology Source Type: research
AbstractObjectiveTo describe trends in outcomes among patients with idiopathic inflammatory myopathies (IIM) over two decades.MethodsFrom 1997 to 2017, a total of 1079 IIM patients were documented in the National Database of the German Collaborative Arthritis Centers. Annual cross-sectional data on treatment, disease activity, patient-reported outcomes, hospitalization and employment were compared across the years. Information on phenotypes, organ manifestations and autoantibodies was collected for a subset to compare the assessment of global health, pain, fatigue and sleeping disorders.ResultsIn 2017, significantly more I...
Source: Rheumatology International - Category: Rheumatology Source Type: research
Abstract Flavonoids are secondary metabolites that are widely distributed in plants. These phenolic compounds are classified into various subgroups based on their structures: flavones, flavonols, isoflavones, flavanones and anthocyanins. They are known to perform various pharmacological actions like antioxidant, anti-inflammatory, anticancer, antimicrobial, antidiabetic and antiallergic, etc. Diabetes is a chronic progressive metabolic disorder that affects several biochemical pathway and leads to secondary complications such as neuropathy, retinopathy, nephropathy and cardiomyopathy. Among them, management of dia...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
Source: Dr. Smith's ECG Blog - Category: Cardiology Authors: Source Type: blogs
This is a re-posting of a Tweet by Robert Jones (@RJonesSonoEM), reproduced with permission, written by Pendell MeyersA middle aged female with history of smoking presented to the ED with " bad heartburn. "Here is her prior baseline ECG (first), and her ED ECG (second):Baseline:ED ECG:What do you think? Do you agree with the computer's interpretation of " Normal ECG " ?This was posted on Twitter and Dr. Smith (and several others) replied that it shows OMI. Dr. Smith said " No " (meaning " No, I do not agree with the computer " ). " New ST elevation in V4-V6. New distortion of S ...
Source: Dr. Smith's ECG Blog - Category: Cardiology Authors: Source Type: blogs
ConclusionWe are reporting a case of unlikely and unusual delayed presentation of retained intervention guide ‐wire post cardiac resynchronization therapy, which was retrieved from the left deltoid muscle.
Source: Journal of Cardiac Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: CASE REPORT Source Type: research
More News: Cardiology | Cardiomyopathy | Children | Databases & Libraries | Genetics | Heart | Pain | Skin | Study | Women