Dysfunction of the foetal arterial duct results in a wide spectrum of cardiovascular pathology.

OBJECTIVE: Foetal ductal problems may have various cardiopulmonary consequences. This study aimed to identify the spectrum of ductus arteriosus (DA) dysfunction (closure, constriction, kinking, aneurysm and thrombosis) and the resultant clinical and echocardiographic presentation in foetuses and neonates. METHODS AND RESULTS: This is a retrospective analysis of serial pre- and post-natal data of 27 cases of foetal ductal dysfunction diagnosed at a median gestational age of 33 weeks (range 20-39). The most common abnormalities observed were premature closure of the DA in 56% (15/27) and constriction in 29% (8/27). Right ventricular hypertrophy was present in 75% (n = 11/15) of foetuses with premature DA closure, while ventricular dilation (4/7, 57%) was a more common feature in foetuses with ductal constriction. After birth, 63% (17/27) of new borns presented with cyanosis and pulmonary hypertension that required active treatment. Three infants died after birth. Abnormalities resolved spontaneously after birth in about 50% of patients. In some children, pulmonary valve stenosis and regurgitation was progressive and required further treatment. CONCLUSIONS: An abnormal right heart on foetal four-chamber ultrasound view should alert the sonographer to the possible presence of foetal ductal dysfunction. Ductal occlusion, transient or fixed constriction, kinking and aneurysm formation are associated with foetal cardiopulmonary sequelae. Symptoms and pathology is probably related to the type, foetal age, rapidity of progression and duration of intrauterine ductal dysfunction. Correspondingly, clinical outcomes vary ranging from little or no symptoms to severe respiratory distress and even foetal or neonatal death.

A mitochondrial tRNA aspartate mutation causing isolated mitochondrial myopathy.

Several mutations in mitochondrial transfer RNA (tRNA) genes can cause mitochondrial myopathy. We describe a young girl who presented with pronounced exercise intolerance. The anaerobic threshold and the maximal oxygen consumption were decreased. She had decreased complex I and IV enzyme activity and ragged red fibers on muscle biopsy. An A to G transition at nucleotide position 7526 in tRNA Aspartate (tRNA(Asp)) gene was heteroplasmic in several of the patient's tissues. We were unable to detect the mutation in muscle tissue from the patient's mother. This case adds a new genetic etiology for mitochondrial myopathy. It also illustrates for patients with combined deficiency of the complex I and IV enzyme activity the value of sequencing in the affected tissue muscle, and not only in blood, all mitochondrial tRNA genes including those not commonly affected, such as in this case mt tRNA(Asp).