Cardiomiopatia mitocôndrica hipertrófica associada à síndrome de Wolff-Parkinson-White

Abstract

490aspartate aminotransferase 147 U/L (normal <37). Due to abnormal serum lactate determination (3.8 µmol/L, normal <2.0), a skeletal muscle biopsy was processed to search for enzymatic activity in the respiratory-chain complex.The patient was transferred to our cardiology hospital at 71 days of age, with tachycardia of 300 beats/min, blood pressure of 90/60 mmHg, mild cyanosis and diaphoresis, and hepatomegaly 3 cm below the costal margin. Due to antiarrhythmic drug resistance (amiodarone maintenance doses 17 mg/kg/day and propranolol 1.5mg qid), clinical heart failure data, mild pericardial effusion, and ventricular dysfunction progression (LVEF ranged 45-54%, FS 21%), radiofrequency catheter ablation became mandatory.She underwent an electrophysiological study 10 days later, under orotracheal intubation and use of midazolam, fentanyl, and propofol i.v. Three multipolar 5 French catheters were inserted by percutaneous femoral access. Groin hemorrhage, acidosis, and hypothermia, followed by ventricular tachycardia and fibrillation, and finally advanced atrio-ventricular block pace dependent, forced us to abandon the procedure. Earlier pacing on the right ventricular apex showed an extremely short ventricle-atrial interval on distal coronary sinus electrodes, compatible with a left atrio-ventricular accessory pathway ( fig.1). The patient evolved to renal dysfunction, a mean blood pressure of 50 mmHg under dopamine-dobutamine infusion, besides intermittent sinus tachycardia and atrio-ventricular reentrant tachycardia that poorly responded to adenosine, either with amiodarone infusion or boluses. One prolonged seizure episode was registered, despite prophylactic phenytoin use, and the patient died 48 hours after the procedure.Partial necropsy (lung and heart) findings included cardiomegaly (73 g; normal for age, 28 g), due to biventricular hypertrophy, with a mean wall thickness of 5 mm for the right ventricle and 14 mm for the left ventricle (normal for age, 1.80 mm and 4.43 mm, respectively). Hematoxylin-eosin and PAS staining revealed gross vacuolar myocyte changes, and discarded lipid or glycogen storage. Electron microscopy showed extensive loss of myofibrils, and augmented size and number of mitochondria, with severe morphological abnormalities and irregularity of the cristae, which were fragmented or had a concentric or peripheral array ( fig.3). A spectrophotometric analysis from skeletal muscle biopsy revealed respiratory chain dysfunction due to a reduction in activity in complex I-III: NADH (nicotinamide adenine dinucleotide dehydrogenase)-cytochrome c reductase (3.81 nmol/min/mg, normal 36-68); complexes I through V were all normal.

Author response: QIL1 is a novel mitochondrial protein required for MICOS complex stability and cristae morphology

“…It has been reported that changes in physiological energetic states and oxygen availability affect the morphology of cristae and CJs (Lorente et al, 2002;Walker and Benzer, 2004), suggesting that the formation of CJs is a dynamic process that promotes cristae remodeling as an adaptive mechanism to the different needs and metabolic states of the cell. Moreover, several mitochondrial disorders in humans are often accompanied by alterations of mitochondrial ultrastructure including MERRF syndrome (Myoclonic epilepsy with ragged red fibers), BTHS (Barth syndrome), fatal neonatal lactic acidosis, mtDNA defects and hypertrophic cardiomyopathy and loss of CJs with the formation of concentric stacks of cristae membrane are some of the hallmarks observed in mitochondria from such patients (Silva-Oropeza et al, 2004;Acehan et al, 2007;Roels et al, 2009;Götz et al, 2012). As such, deciphering how CJs and CSs are formed and regulated is crucial for the understanding of cristae dynamics and maintenance in health and disease.…”