Fatal respiratory failure in a full-term newborn with two ABCA3 gene mutations: a case report.

Genetic mutations associated with pulmonary surfactant protein deficiency are associated with diverse clinical phenotypes. Mutations of the surfactant protein B and C genes were the first to be described. In 2004, fatal surfactant deficiency in newborns due to mutations of the gene encoding the adenosine triphosphate-binding cassette transporter A3 (ABCA3) was first reported. Few cases of lethal adenosine triphosphate-binding cassette transporter A3 mutations have been described to date. In our report, we describe a full-term newborn that died because of respiratory failure secondary to an uncommon ABCA3 genetic configuration.

[Respiratory diseases associated to surfactant proteins B and C deficiency]. / Malattie respiratorie associate a deficit delle proteine B e C del surfattante.

Pulmonary surfactant is a mixture of lipids and proteins necessary to reduce alveolar surface tension and prevent end expiratory atelectasis. The hydrophobic surfactant proteins B and C are essential for lung function and pulmonary homeostasis after birth. Mutations in the genes encoding surfactant proteins B and C are associated with acute respiratory failure and interstitial lung disease. Diagnosis is possible through DNA analysis from blood leucocytes and immunostaining from lung tissue.

Congenital misalignment of pulmonary vessels and alveolar capillary dysplasia: how to manage a neonatal irreversible lung disease?

Congenital misalignment of pulmonary vessels (MPV) with alveolar capillary dysplasia is a rare condition consisting of anomalous veins in bronchovascular bundles, a decreased number of alveolar capillaries, and increased muscularization of pulmonary arterioles. In the literature, infants reported as having such a malformation developed respiratory distress with persistent pulmonary hypertension and ultimately died. We report the case of an infant with MPV and alveolar capillary dysplasia who was unresponsive to maximal cardiorespiratory support, including high-frequency oscillatory ventilation and inhaled nitric oxide; the infant died of pulmonary hemorrhage after 19 days, during venoarterial extracorporeal membrane oxygenation bypass. We conclude that the diagnosis of MPV and alveolar capillary dysplasia should be considered during autopsy of infants who have died of irreversible persistent pulmonary hypertension. If a lung biopsy in infants with prolonged refractory hypoxemia confirms such diagnosis before death, expensive and invasive treatments such as extracorporeal membrane oxygenation could be avoided.

Hereditary surfactant protein B deficiency resulting from a novel mutation.

Hereditary surfactant protein B (SP-B) deficiency is an autosomal recessive disease in which affected infants are unable to produce normally functional surfactant, resulting in neonatal respiratory failure and death within the first year of life. The most common cause of SP-B deficiency is a frameshift mutation in exon 4 (121ins2) of the SP-B gene. We report a newborn infant who had onset of respiratory distress during the first days, was unresponsive to exogenous surfactant, corticosteroids, prostacyclin, high frequency oscillatory ventilation and inhaled nitric oxide, and died after 27 days. Immunostaining of lung tissue obtained at biopsy demonstrated absent staining for SP-B, and robust extracellular staining for proSP-C, findings characteristic for SP-B deficiency. DNA analysis revealed the 121ins2 mutation on one of her SP-B alleles and a novel mutation, 122delC, on her other SP-B allele. The proximity of the novel mutation in exon 4 allele found in this infant to the 121ins2 supports the notion that this region may represent a "hot spot" for SP-B gene mutations and confirms the heterogeneity of mechanisms which lead to SP-B deficiency. Hereditary SP-B deficiency is a rare, newly diagnosable and probably under-recognized disease, which should be suspected in term newborn infants with unexplained respiratory failure.

Imaging of neonatal hemangiomas, two cases.

Hemangiomas are the most common tumor of infancy. Most hemangiomas are harmless and follow a benign clinical course and undergo regression with time. Sometimes they can destroy vital organs and become life-threatening. We report two cases of neonatal hemangiomas which presented very different clinical aspects and course.

Reduction of haemorrhagic complications during mechanically assisted circulation with the use of a multi-system anticoagulation protocol.

Two different anticoagulation protocols were used in 49 consecutive patients mechanically supported either for bridge to transplantation (11) or for recovery of myocardial function after cardiac surgery (35). In 46 patients a Biomedicus centrifugal pump was used and in 3 patients a Pierce-Donachy ventricles. Mechanical support was provided to the left ventricle in 14 patients, to the right ventricle in 6 and to both ventricles in 12 patients; an extra-corporeal membrane oxygenator (ECMO) support was used in 17 patients. Thirty-seven males and 12 females, aged 0.2 to 58 years, were supported for an average time of 6.3 days (range 1-43). Anticoagulation was either based on a continuous infusion of heparin in the first 27 patients (group A) or on a multi-system therapy ("La Pitié" protocol) in the other 22 patients (group B). Overall survival rate was 47%. Patients in group A had a 30% (8/27) survival rate, whereas in group B a 68% (15/22) survival rate was observed (p = 0.006). Transplantation and ventricular assist device (VAD) removal was successfully obtained in 59% (16/27) and 91% (20/22) of patients in group A and group B respectively (p = 0.05). Significant bleeding occurred in 21 patients (81%) in group A and in 2 (9%) of group B (p = 0.001). In these patients bleeding averaged 230 +/- 231 ml/kg in group A versus 55 +/- 18 ml/kg in group B (p = 0.001). Surgical revision was necessary for cardiac tamponade or persistent bleeding in 12 patients of group A (25 procedures: mean 0.9/patient) and in 3 patients of group B (one each patient: mean 0.1/patient) (p = 0.01). Infection, thrombo-embolism and brain hemorrhage were also less frequent in group A than in group B. Our data suggest that the "La Pitié" protocol provides a better control of bleeding than the conventional heparin infusion in patients receiving assist device. this reduction in thrombo-hemorrhagic complications might improve the results of mechanical circulatory support.