A fatal case of neonatal onset multiple acyl-CoA dehydrogenase deficiency caused by novel mutation of ETFDH gene: case report.

BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) or glutaric aciduria type II is an extremely rare autosomal recessive inborn error of fatty acid beta oxidation and branched-chain amino acids, secondary to mutations in the genes encoding the electron transfer flavoproteins A and B (ETFs; ETFA or ETFB) or ETF dehydrogenase (ETFDH). The clinical manifestation of MADD are heterogeneous, from severe neonatal forms to mild late-onset forms. CASE PRESENTATION: We report the case of a preterm newborn who died a few days after birth for a severe picture of untreatable metabolic acidosis. The diagnosis of neonatal onset MADD was suggested on the basis of clinical features displaying congenital abnormalities and confirmed by the results of expanded newborn screening, which arrived the day the newborn died. Molecular genetic test revealed a homozygous indel variant c.606 + 1 _606 + 2insT in the ETFDH gene, localized in a canonical splite site. This variant, segregated from the two heterozygous parents, is not present in the general population frequency database and has never been reported in the literature. DISCUSSION AND CONCLUSION: Recently introduced Expanded Newborn Screening is very important for a timely diagnosis of Inherited Metabolic Disorders like MADD. In some cases which are the most severe, diagnosis may arrive after symptoms are already present or may be the neonate already died. This stress the importance of collecting all possible samples to give parents a proper diagnosis and a genetic counselling for future pregnacies.

Therapy Of Cardiac Arrhythmias In Children: An Emerging Role Of Electroanatomical Mapping Systems.

INTRODUCTION: Cardiac arrhythmias are challenging diseases in childhood. Most of them in pediatric subjects (90.2%) are atrioventricular reentrant tachycardias and atrioventricular nodal reentrant tachycardias. The standard 12-lead ECG is a highly accurate diagnostic tool but an invasive electrophysiological study is often required. The main concern about this kind of procedures is their invasive nature and the need of radiations, so antiarrhythmic agents are currently the first line therapy. However, they often show side effects and can be insufficient for the rate control. MATERIALS AND METHODS: We performed a systematic research on Embase and PubMed. We found 563 articles and selected the most representative 50. DISCUSSION: Management of cardiac arrhythmias could be very difficult in several scenarios, especially in children with body weight <15 kg and age <4 years. In general, pediatric subjects show a cumulative risk of malignancy greater than adults, having greater life expectancy. On this basis the guiding principle during radiation delivery in electrophysiological procedures is "as low as reasonably achievable" (acronym: ALARA). The development of 3-dimensional (3D) electroanatomical mapping systems allowed significant reduction of exposure. The most recently reported experiences demonstrate safety and feasibility of fluoroless ablation in the most common arrhythmias in children, even in challenging conditions. CONCLUSION: The first reasonable approach in cardiac arrhythmias involving younger patients seems to be pharmacological. However antiarrhythmic drugs pose problems both in terms of side effects and often have poor efficacy. Expertise in electrophysiological techniques is constantly increasing and the development of new technologies allow us to encourage the use of electroanatomical mapping systems in order to reduce the radiation exposure in children undergoing to catheter ablation, especially for accessory pathways.

[Congenital valvular heart disease with high familial penetrance]. / Valvulopatia congenita ad elevata penetranza familiare.

Bicuspid valve aortic (BVA) is one of the most common congenital malformations. Only 20% of patients preserves a normal valve function throughout life. There are sporadic and familial forms, the latter to autosomal dominant. We present a case of familiarity of BVA high penetrance. Patient with aortic stenosis by BVA, is the father of two children with BVA.

Treatment failure of low molecular weight heparin in a patient with an aortic mechanical prosthesis.

After mechanical heart valve replacement use of unfractionated heparin is sometimes required because vitamin K antagonists are temporarily contraindicated or to prevent valve-associated thromboembolism until oral vitamin K antagonists take effect. Bridging therapy with a standardized low molecular weight heparin-based regimen has been reported effective and relatively safe in a large cohort of patients with mechanical heart valves. Many cases with mitral mechanical valve prostheses and treatment failure of low molecular weight heparin have also been reported as well as prosthetic valve thrombosis has been reported with adequate anticoagulation. A case has also been reported of well functioning Starr-Edwards aortic prosthesis without anticoagulation. We present a case of cardioembolic stroke in a patient with an aortic mechanical prosthesis in bridging therapy with a standardized low molecular weight heparin-based regimen. This case is illustrative of treatment failure of low molecular weight heparin in a patient with an aortic mechanical prosthesis.

An occasional diagnosis of isolated pulmonary stenosis.

Pulmonary stenosis can occur as part of more congenital cardiac malformations or as rare primary isolated pulmonary stenosis. It has been reported a primary isolated pulmonary artery stenosis in an asymptomatic 25-day-old newborn infant and a rare case of isolated pulmonary stenosis in a 66-year-old woman has been reported too. We present a case of primary isolated pulmonary artery stenosis in an asymptomatic 11-year-old Italian woman where the diagnosis was made during a cardiovascular check-up.

Perinatal asphyxia and cardiac abnormalities.

The most common etiologies of myocardial infarction in the perinatal period are congenital heart disease, coronary artery lesions, thromboembolism and perinatal asphyxia. Cardiac abnormalities in perinatal asphyxia include tricuspid regurgitation and mitral regurgitation associated with transient myocardial ischemia of the newborn. Patent foramen ovale is a frequent remnant of the fetal circulation. Persistent hypoxia sometimes causes pulmonary arterial hypertension with consequent right to left shunt across patent ductus arteriosus and foramen ovale. We describe a case of tricuspid regurgitation, mitral regurgitation, and patent foramen ovale in a 15-day-old newborn male infant with a history of perinatal asphyxia. Also this case focuses attention on the perinatal asphyxia.

A recurrent patent ductus arteriosus.

Patent ductus arteriosus (PDA) can occur as part of more congenital cardiac malformations or as an isolate finding. Spontaneous, transcatheter, surgical closure, and pharmacological treatment have been reported. We present a case of recurrent PDA after the initial course of a pharmacological treatment. Also this case focuses on recurrent PDA after the initial course of a pharmacological treatment.

A case of spontaneous closure of a muscular ventricular septal defect.

Ventricular septal defects can occur as part of more congenital cardiac malformations or as an isolate finding. Surgical closure, transcatheter occlusion and spontaneous closure have been reported. We present a case of spontaneous closure of a muscular ventricular septal defect. This case focuses attention on spontaneous closure of a muscular ventricular septal defect.

The chance finding of an aneurysm of the right sinus of Valsalva in an 11-year-old child with a ventricular septal defect and a pericardial effusion.

Ventricular septal defects can occur as part of other congenital cardiac malformations or as an isolated finding. Aneurysms of the sinus of Valsalva are rare, most commonly involving the right or noncoronary sinuses. They can be congenital or acquired through infection, trauma, or degenerative diseases. They frequently co-exist with ventricular septal defects, aortic valve dysfunction, or other cardiac abnormalities. More commonly, sinus of Valsalva aneurysms are diagnosed after the clinical sequelae of rupture. Several etiologic factors may lead to the development of pathologic pericardial effusion and the detection of pericardial effusion was one of the first applications of echocardiography to gain widespread acceptance. We present a case of a chance finding of an aneurysm of the right sinus of Valsalva in an 11-year-old Italian child with a ventricular septal defect and a pericardial effusion.

The chance finding of a ventricular septal defect in a 2-day-old newborn infant.

Certain congenital cardiac defects may go undetected for several years due to lack of symptoms and signs.Ventricular septal defects can occur as part of more congenital cardiac malformations or as an isolate finding. The natural history of ventricular septal defects depends on the size of the defect and on the pulmonary resistance. We present a case of the chance finding of a ventricular septal defect in a 2-day-old newborn infant with an interatrial septal aneurysm.

Interatrial defect and patent ductus arteriosus.

We greatly appreciated the letter to the Editor by Rana Olgunturk and Serdar Kula. We can say that his interpretation coincides with our interpretation and with the knowledge about patent ductus arteriosus (PDA) and secundum atrial septal defects. Although functional closure of PDA usually occurs in the first few hours of life in healthy infants born at term (about 15 h of life in healthy infants born at term), true anatomic closure, in which the ductus loses the ability to reopen, may take several weeks. Persistent, patency for up to 10 days after birth is encountered in premature infants. The male Italian newborn infant of the cited case report was referred at the age of 2 days to the Cardiology Unit for a cardiovascular check-up (in the text: "in a 3-day-old newborn infant" must be comprehended as "in a 2-day-old newborn infant") and was mature. Interatrial septal shunts in newborns are frequently encountered. Since there are no definitive diagnostic criteria for both patent foramen ovale and secundum atrial septal defects, it is difficult to differentiate these two lesions by echocardiography, particularly in the early newborn period. Some authors, called these two lesions as "interatrial septal openings". The diagnosis, in the case report cited, was made not only on the basis of the first observation but also on the basis of the persistence of abnormalities during the long-term follow-up and therefore the infant was referred to a pediatric heart surgical unit were the abnormalities were confirmed.

A congenital form of junctional ectopic tachycardia.

Accessory pathways have been described as well as their Ecg identification criteria also in pediatric population. Radiofrequency ablation is a curative treatment but its application has been more limited in the paediatric population. The congenital form of junctional ectopic tachycardia was firstly described by Coumel et al. in 1976. It usually occurs in the first six months of life presenting as a persistent sustained form, lasting up to 90% of the time and it is hampered by high mortality. Its clinical presentation may be dramatic, being associated in up to 60% of cases with cardiomegaly and/or heart failure. Secondary dilated cardiomyopathy, ventricular fibrillation and sudden cardiac death have also been reported. We present a case of congenital form of junctional ectopic tachycardia in a 12-day-old newborn infant. Also this case is illustrative of the congenital form of junctional ectopic tachycardia.

Interatrial defect, ventricular septal defect and patent ductus arteriosus in a 2-day-old newborn infant.

Interatrial defects, ventricular septal defects, and patent ductus arteriosus can occur as part of more congenital cardiac malformations or as an isolate finding. We present a case of interatrial defect associated with ventricular septal defect and patent ductus arteriosus in a 2-day-old newborn infant.