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:

CONCLUSION: Herpes simplex virus hepatitis causes significant morbidity, and pregnant women are susceptible to severe infections. Pregnant or peripartum women with acute febrile hepatitis require prompt evaluation for HSV with serum PCR screening. PMID: 31923059 [PubMed - as supplied by publisher]
Source: Obstetrics and Gynecology - Category: OBGYN Authors: Tags: Obstet Gynecol Source Type: research
Authors: Lindow T, Pahlm O, Khoshnood A, Nyman I, Manna D, Engblom H, Lassen AT, Ekelund U Abstract Objectives. Pericarditis, takotsubo cardiomyopathy and early repolarization syndrome (ERS) are well-known to mimic ST elevation myocardial infarction (STEMI). We aimed to study whether ECG findings of reciprocal ST depression, PR depression, ST-segment convexity or terminal QRS distortion can discriminate between ST elevation due to ischemia and non-ischemic conditions. Design. Eighty-five patients with STEMI and 94 patients with non-ischemic ST elevation were included. All patients had acute chest pain and at least ...
Source: Scandinavian Cardiovascular Journal - Category: Cardiology Tags: Scand Cardiovasc J Source Type: research
AbstractTakotsubo cardiomyopathy (TC) is a significant cause of acute heart failure in adults. However, triggering factors, ECG and echocardiographic findings, and prognosis of TC have not been well studied in children. Therefore, this study aimed to evaluate the demographic characteristics, signs and symptoms, laboratory findings, and prognosis of children with TC. We analyzed demographic characteristics of childhood TC cases (aged
Source: European Journal of Pediatrics - Category: Pediatrics Source Type: research
We described phenotypes and outcomes of cardiotoxic cases. RESULTS: We identified 177 patients who received fluoropyrimidines. After adjudication, 4.5% of the cohort met the criteria for cardiovascular toxicity. Coronary artery disease was more common among cases than controls (38% vs. 7%, p
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
Authors: von Kodolitsch Y, Demolder A, Girdauskas E, Kaemmerer H, Kornhuber K, Muino Mosquera L, Morris S, Neptune E, Pyeritz R, Rand-Hendriksen S, Rahman A, Riise N, Robert L, Staufenbiel I, Szöcs K, Vanem TT, Linke SJ, Vogler M, Yetman A, De Backer J Abstract Introduction: The revised Ghent nosology presents classical features of Marfan syndrome. However, behind its familiar face, Marfan syndrome hides less well-known features.Areas covered: The German Marfan Organization listed unusual symptoms and clinical experts reviewed the literature on clinical features of Marfan syndrome not listed in the Ghent nosol...
Source: Expert Review of Cardiovascular Therapy - Category: Cardiology Tags: Expert Rev Cardiovasc Ther Source Type: research
By AMEYA KULKARNI, MD When Samuel Morse left his New Haven home to paint a portrait of the Maquis du Lafayette in Washington DC, it was the last time he would see his pregnant wife. Shortly after his arrival in Washington, his wife developed complications during childbirth. A messenger took several days on horseback to relay the message to Mr Morse. Because the trip back to New Haven took several more, his wife had died by the time he arrived at their home.  So moved was he by the tragedy of lost time that he dedicated the majority of the rest of his life to make sure that this would never happen to anyone again. H...
Source: The Health Care Blog - Category: Consumer Health News Authors: Tags: Health Policy Medical Practice Ameya Kulkarni Global Health Maternal mortality public health Source Type: blogs
A 50-something with sudden severe epigastric and chest pain presented looking extremely ill.Here is her ECG:What do you think?There is ST Elevation in V2-V6, worrisome for ischemia.Or is it?Notice the very large R-waves and the very prominent J-point notching, with small S-waves.This is typical ofBenign T-wave Inversion, which is commonly seen in black patients of African heritage.This case was sent from Australia and the patient was aboriginal.  I have never heard of or seen benign T-wave inversion in Australian aboriginal blacks.The cath lab was activated and the patient was taken for angiogram, which was norma...
Source: Dr. Smith's ECG Blog - Category: Cardiology Authors: Source Type: blogs
ConclusionCecal volvulus should be kept in mind in a child presenting with signs suggestive of intestinal obstruction.
Source: International Journal of Surgery Case Reports - Category: Surgery Source Type: research
CONCLUSION: This case report provides an insight into the diagnosis and management of TTC in the absence of pathognomic features. PMID: 31752657 [PubMed - as supplied by publisher]
Source: Current Cardiology Reviews - Category: Cardiology Tags: Curr Cardiol Rev Source Type: research
Written by Meyers, edits by SmithA 50-ish year old man was working construction when he suddenly collapsed. Coworkers started CPR within 1 minute of collapse. EMS arrived within 10 minutes and continued CPR and ACLS, noting alternating asystole and sinus bradycardia during rhythm checks. He received various ACLS medications and arrived at the ED with a perfusing rhythm.Initial vitals included heart rate around 100 bpm and BP 174/96. Here is his initial ECG, very soon after ROSC:What do you think?Sinus tachycardia.  There is incomplete RBBB (QRS duration less than 120 ms).  There is diffuse STD, maximal in V4-V5 a...
Source: Dr. Smith's ECG Blog - Category: Cardiology Authors: Source Type: blogs
More News: Cardiology | Cardiomyopathy | Children | Databases & Libraries | Genetics | Heart | Pain | Skin | Study | Women