scholarly journals A Mild Phenotype of Mitochondrial DNA Depletion Syndrome Type 13 with a Novel FBXL4 Variant

2021 ◽  
pp. 1-6
Author(s):  
Ummuhan Oncul ◽  
Engin Kose ◽  
Fatma Tuba Eminoglu
Keyword(s):  
Mitochondrial Dna ◽  
Genetic Disorders ◽  
Clinical Signs ◽  
Gene Mutations ◽  
Signs And Symptoms ◽  
Left Ventricular ◽  
Facial Dysmorphism ◽  
Mild Phenotype ◽  
Psychomotor Delay ◽  
Mitochondrial Dna Depletion

Mitochondrial DNA depletion syndromes (MDDS) are a group of rare genetic disorders caused by defects in multiple genes involved in mitochondrial DNA maintenance. Among these, <i>FBXL4</i> gene variants result in encephalomyopathic mtDNA depletion syndrome 13 (MTDPS13), which commonly presents as a combination of failure to thrive, neurodevelopmental delays, encephalopathy, hypotonia, a pattern of mild facial dysmorphisms, and persistent lactic acidosis. To date, 53 pathogenic <i>FBXL4</i> variants and 100 cases have been described in the literature. In the present case report, we report on a 4.5-year-old boy with MTDPS13 and a novel variant. The patient had a history of antenatal hydrocephalus, severe developmental delay and mental motor retardation with psychomotor delay, severe hypotonia, mild left ventricular hypertrophic cardiomyopathy, mild facial dysmorphism, and elevated lactate levels. Symptoms suggested mitochondrial myopathy; subsequently, whole-exome sequencing was performed and a novel homozygous variant <i>FBXL4</i> (NM_012160.4): c.486T&#x3e;G (p.Tyr162Ter) was identified. While most of the patients with <i>FBLX4</i> gene mutation have severe clinical manifestation and die at a very young age, clinical progress of our case was milder than previously reported. MDDS are very rare and can present with many different clinical signs and symptoms. In this report, we identified a novel pathogenic variant in the <i>FBXL4</i> gene. This report shows that patients with <i>FBLX4</i> gene mutations may present with a milder clinical phenotype than previously reported.

scholarly journals Function of the left ventricular myocardium in patients with systemic sclerosis

2010 ◽  
Vol 63 (3-4) ◽  
pp. 163-169
Author(s):  
Marina Deljanin-Ilic ◽  
Stevan Ilic ◽  
Bojana Stamenkovic
Keyword(s):  
Cardiovascular Disease ◽  
Systemic Sclerosis ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Ventricular Myocardium ◽  
Tissue Doppler ◽  
Left Ventricular ◽  
Doppler Imaging ◽  
Left Ventricular Myocardium ◽  
Female Patients

Deposits of myocardial fibrosis are the principal cause of myocardial dysfunction and poor prognosis in the patients with systemic sclerosis. Our aim was to assess whether there are changes in regional function of the left ventricular myocardium in female patients with systemic sclerosis without clinical signs and symptoms of cardiovascular disease. The study included 23 female patients with systemic sclerosis (without cardiovascular disease and with normal global systolic and diastolic function of the left ventricle) and 21 healthy female controls. In both groups, pulsed wave tissue Doppler imaging was done at rest and during exercise stress test echocardiography. The myocardial function was assessed from the basal segments in systola and diastola. The level achieved and duration of exercise tests were significantly reduced in the patients with systemic sclerosis compared to the controls (P<0.001 for both). The patients had significantly lower baseline regional systolic (P<0.02) and diastolic (P<0.001) myocardial functions, which became even more evident after the exercise test. During the test, those with systemic sclerosis demonstrated a smaller increase of systolic (20.6%) and diastolic (6.5%) function compared to the controls (systolic by 32.3% and diastolic by 25.0%). Quantification of regional function of the left ventricular myocardium using pulsed wave tissue Doppler imaging demonstrated an impaired systolic and diastolic myocardial function in the female patients with systemic sclerosis who had no clinical signs and symptoms of a cardiovascular disease.

scholarly journals Myotonic Dystrophy Initially Presenting as Tachycardiomyopathy Successful Catheter Ablation of Atrial Flutter

2010 ◽  
Vol 2010 ◽  
pp. 1-4 ◽  
Author(s):  
S. Asbach ◽  
K. J. Gutleben ◽  
P. Dahlem ◽  
J. Brachmann ◽  
G. Nölker
Keyword(s):  
Heart Failure ◽  
Catheter Ablation ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Atrial Flutter ◽  
Myotonic Dystrophy ◽  
Sinus Bradycardia ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Left Ventricular

Myotonic dystrophy is a genetic muscular disease that is frequently associated with cardiac arrhythmias. Bradyarrhythmias, such as sinus bradycardia and atrioventricular block, are more common than tachyarrhythmias. Rarely, previously undiagnosed patients with myotonic dystrophy initially present with a tachyarrhythmia. We describe the case of a 14-year-old boy, who was admitted to the hospital with clinical signs and symptoms of decompensated heart failure and severely reduced left ventricular function. Electrocardiography showed common-type atrial flutter with 2 : 1 conduction resulting in a heart rate of 160 bpm. Initiation of medical therapy for heart failure as well as electrical cardioversion led to a marked clinical improvement. Catheter ablation of atrial flutter was performed to prevent future cardiac decompensations and to prevent development of tachymyopathy. Left ventricular function normalized during followup. Genetic analysis confirmed the clinical suspicion of myotonic dystrophy as known in other family members in this case.

scholarly journals New DGK Gene Mutations in the Hepatocerebral Form of Mitochondrial DNA Depletion Syndrome

2005 ◽  
Vol 62 (5) ◽  
pp. 745 ◽  
Author(s):  
Michelangelo Mancuso ◽  
Silvio Ferraris ◽  
Jacklyn Pancrudo ◽  
Annette Feigenbaum ◽  
Julian Raiman ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Gene Mutations ◽  
Mitochondrial Dna Depletion ◽  
Mitochondrial Dna Depletion Syndrome

scholarly journals Adult mitochondrial DNA depletion syndrome with mild manifestations

2013 ◽  
Vol 5 (2) ◽  
pp. 9 ◽  
Author(s):  
Josef Finsterer ◽  
Gabor G. Kovacs ◽  
Uwe Ahting
Keyword(s):  
Mitochondrial Dna ◽  
Family History ◽  
Mitochondrial Disorder ◽  
Clinical Manifestations ◽  
Exercise Intolerance ◽  
Mild Phenotype ◽  
Lower Limb Muscles ◽  
Mitochondrial Dna Depletion ◽  
History Of ◽  
Mitochondrial Dna Depletion Syndrome

Mitochondrial DNA depletion syndrome (MDS) is usually a severe disorder of infancy or childhood, due to a reduced copy number of mtDNA molecules. MDS with only mild, non-specific clinical manifestations and onset in adulthood has not been reported. A 47-year-old Caucasian female with short stature and a history of migraine, endometriosis, Crohn’s disease, C-cell carcinoma of the thyroid gland, and a family history positive for mitochondrial disorder (2 sisters, aunt, niece), developed day-time sleepiness, exercise intolerance, and myalgias in the lower-limb muscles since age 46y. She slept 9-10 hours during the night and 2 hours after lunch daily. Clinical exam revealed sore neck muscles, bilateral ptosis, and reduced Achilles tendon reflexes exclusively. Blood tests revealed hyperlipidemia exclusively. Nerve conduction studies, needle electromyography, and cerebral and spinal magnetic resonance imaging were non-informative. Muscle biopsy revealed detached lobulated fibers with subsarcolemmal accentuation of the NADH and SDH staining. Real-time polymerase chain reaction revealed depletion of the mtDNA down to 9% of normal. MDS may be associated with a mild phenotype in adults and may not significantly progress during the first year after onset. In an adult with hypersomnia, severe tiredness, exercise intolerance, and a family history positive for mitochondrial disorder, a MDS should be considered.

High level of oxysterols in neonatal cholestasis: a pitfall in analysis of biochemical markers for Niemann-Pick type C disease

2016 ◽  
Vol 54 (7) ◽  
Author(s):  
Giulia Polo ◽  
Alessandro Burlina ◽  
Francesca Furlan ◽  
Thilini Kolamunnage ◽  
Mara Cananzi ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Gene Mutations ◽  
Signs And Symptoms ◽  
Niemann Pick Disease ◽  
Liquid Chromatography Tandem Mass ◽  
Type C ◽  
Clinical Signs And Symptoms ◽  
Niemann Pick ◽  
High Level ◽  
Negative Controls

AbstractNiemann-Pick disease type C (NPC) is a rare lipid storage disorder characterized by progressive neurological deterioration. Diagnosing NPC is challenging as clinical signs and symptoms are variable and non-specific. Two oxysterols, cholestane-3β,5α,6β-triol (triol) and 7-ketocholesterol (7KC), have been proposed as biomarkers for aiding diagnosis of NPC. This study evaluated the use of triol and 7KC as biomarkers in cholestatic neonates with suspected NPC.Plasma triol and 7KC were analysed as dimethylglycine esters using an liquid chromatography – tandem mass spectrometry (LC-MS/MS) assay in selected neonates with severe cholestasis and suspected NPC (n=7), adults with cholestasis (n=15), patients with confirmed NPC (positive controls; n=11 [one child and 10 adults]), healthy subjects (negative controls; n=40 [20 children and 20 adults]), and cholestatic adults (comparative reference; n=15). The LC-MS/MS method was subjected to a number of tests for accuracy and consistency.Triol and 7KC levels were substantially and significantly increased in NPC positive patients compared with healthy controls (p<0.001). However, positive results (markedly increased levels of both oxysterols) were identified in 6/7 (86%) neonates with cholestasis. Genetic testing confirmed NPC only in one neonate who had increased triol and 7KC, and increased oxysterol levels among neonates with no identified NPC gene mutations were considered likely due to biliary atresia (BA).While the potential of oxysterols as NPC biomarkers has been well evaluated in older patient populations (without cholestasis), our data suggest that cholestasis might represent a pitfall in oxysterol measurements intended to aid diagnosis of NPC in affected patients.

scholarly journals ASPEK GENETIK TALASEMIA

2013 ◽  
Vol 1 (3) ◽  
Author(s):  
Joyce Regar
Keyword(s):  
Family History ◽  
Life Span ◽  
Genetic Factor ◽  
Genetic Disorders ◽  
Genetic Disorder ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Laboratory Examinations ◽  
Clinical Signs And Symptoms ◽  
Haemoglobin Synthesis

Abstract: Genetic disorders are caused by the presence of affected genes. Thalassaemia, a kind of anaemia due to a genetic disorder, reveals defects in haemoglobin synthesis and chain balance. Signs and symtomps depend on the severity of this disease which vary from slight anemia to facies Cooley, the main characteristic of thalassaemia patients. Diagnosis of thalassaemia is based on clinical signs and symptoms, ethnicity, family history, laboratory examinations, and other supporting examinations. Good management can prolong the life span of thalassaemia patients. Key words: thalassaemia, genetic factor, haemoglobin Abstrak: Penyakit genetik adalah penyakit yang disebabkan oleh karena adanya kelainan dalam susunan gen seseorang. Talasemia merupakan salah satu jenis anemia akibat adanya defek dalam sintesis hemoglobin dan keseimbangan rantainya dengan faktor genetik sebagai penyebab utama. Gejala yang timbul tergantung tingkat keparahan penyakit ini, mulai dari anemia ringan hingga facies Cooley yang merupakan ciri khas pengidap talasemia. Diagnosis talasemia dapat ditegakkan berdasarkan gejala klinik, asal etnis, riwayat keluarga, pemeriksaan keluarga, pemeriksaan laboratorium, dan pemeriksaan penunjang lainnya. Penatalaksanaan yang baik dapat memperpanjang masa hidup dari penderita talasemia. Kata kunci: talasemia, faktor genetik, hemoglobin

scholarly journals Dysphagia as an early presentation of Di George's Syndrome- case report

2021 ◽  
Vol 13 (1) ◽  
pp. 1-6
Author(s):  
Snezana Palchevska ◽  
Beti Gjurkova ◽  
Elena Shukarova ◽  
Katarina Stavrikj ◽  
Jana Jovanovska ◽  
...  
Keyword(s):  
Vascular Ring ◽  
Clinical Signs ◽  
Vascular Anomaly ◽  
Signs And Symptoms ◽  
Lateral View ◽  
Facial Dysmorphism ◽  
Preterm Baby ◽  
Early Presentation ◽  
Feeding Difficulties ◽  
Cardiovascular Anomalies

DiGeorge’s syndrome is a 22q11.2 deletion leading to abnormal embryogenesis of pharyngeal arches and it is manifesting in a variety of clinical signs and symptoms. The spectrum of anomalies varies from minor facial dysmorphism and cleft palate to a broad spectrum of cardiovascular anomalies, thymic disfunction and immune deficiencies, hypocalcemia due tohypoparathyroidism,growth and developmental delay and speech disturbances. Cardiovascular anomalies might include right sided aortic arch, aberrant vesiclesand vascular ring. Here we present an atypical case of partial DiGeorge’s syndrome with feeding and swallowing difficulties and laryngeal stridor in the neonatal period. Early presentation in this period is usually due to severe hypocalcemia and cardiac disease. Feeding difficulties in a preterm baby needed clinical assessment skills in order to establish the diagnosis and delineate it from feeding difficulties usually seen in preterm babies. Esophagogram (barium X Ray) showed antero-posterior oblique impression towards the right side, the latero- lateral view showed impression on the rare side, suspected to be esophageal sub stenosis due to vascular anomaly, aberrant right subclavian arteryand suspectedthymic hypoplasia. We report a 9-year follow up periodbya team of subspecialists. The child had two surgeries due to aberrant vessel and velopharyngeal deficiency. Optimal management of patients with DiGeorge’s syndrome requires a multidisciplinary teamwhichshould include a cardiologist, immunologist, geneticist, speech/language therapist, endocrinologist and other subspecialists depending on patient`'s phenotype.

Chronic heart failure management and remote haemodynamic monitoring

Heart ◽  
2018 ◽  
Vol 104 (23) ◽  
pp. 1910-1919 ◽  
Author(s):  
Aaron M Wolfson ◽  
Michael Fong ◽  
Luanda Grazette ◽  
Joseph E Rahman ◽  
David M Shavelle
Keyword(s):  
Heart Failure ◽  
Remote Monitoring ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Haemodynamic Monitoring ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Clinical Signs And Symptoms

Heart failure (HF) has a large societal and economic burden and is expected to increase in magnitude and complexity over the ensuing years. A number of telemonitoring strategies exploring remote monitoring and management of clinical signs and symptoms of congestion in HF have had equivocal results. Early studies of remote haemodynamic monitoring showed promise, but issues with device integrity and implantation-associated adverse events hindered progress. Nonetheless, these early studies established that haemodynamic congestion precedes clinical congestion by several weeks and that remote monitoring of intracardiac pressures may be a viable and practical management strategy. Recently, the safety and efficacy of remote pulmonary artery pressure-guided HF management was established in a prospective, single-blind trial where randomisation to active pressure-guided HF management reduced future HF hospitalisations. Subsequent commercial use studies reinforced the utility of this technology and post hoc analyses suggest that tight haemodynamic management of patients with HF may be an additional pillar of therapy alongside established guideline-directed medical and device therapy. Currently, there is active exploration into utilisation of this technology and management paradigm for the timing of implantation of durable left ventricular assist devices (LVAD) and even optimisation of LVAD therapy. Several ongoing clinical trials will help clarify the extent and utility of this strategy along the spectrum of patient with HF from individuals with chronic, stable HF to those with more advanced disease requiring heart replacement therapy.

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