Prolonged survival in alveolar capillary dysplasia syndrome

Abstract

Survival for up to 101 days is reported in an infant with congenital alveolar capillary dysplasia (ACD) with misalignment of pulmonary veins using inhaled nitric oxide thereby offering the prospect of survival until lung transplantation can be performed.The patient was a 3040 g Caucasian girl delivered at 39 weeks gestation. She developed cyanosis, tachypnoea, and hypoxaemia at 12 h of age. Echocardiography demonstrated atrial and ductal right-to-left shunt and suprasystemic right ventricular pressure. Following evaluation of the effect of different dosages of inhaled nitric oxide (iNO) during cardiac catheterisation, the therapeutic dose was chosen to be between 2-10 ppm, with a target O 2 saturation of 95%. Right ventricular pressure decreased from 90-110 mmHg before to 60-65 mmHg after starting NO inhalation. Mean systolic arterial blood pressure was 55-75 mmHg. Breathing rate ranged from 30 to 50/min. A sibling had died 5 years earlier at the age of 17 days from a similar clinical presentation and ACD had been diagnosed at autopsy.At the age of 23 days, an open lung biopsy was performed. Pulmonary lobules were abnormally developed and showed thickened immature septa.Alveolar capillaries were frequently located in a central position deep inside the septa and were rarely in contact with the alveolar epithelium. Pulmonary veins could be found within the bronchovascular bundles adjacent to the pulmonary arteries instead of their normal intra-acinar course away from the arterial branches (''misalignment''). Pulmonary arteries showed thickened muscular walls reflecting persistent pulmonary hypertension. In addition, prematurely muscularised arterioles were found within the pulmonary acini, the typical findings of ACD combined with misalignment of pulmonary veins (MPV). Pathological changes in ACD/MPV resemble a normal fetal lung at the canalicular stage and can therefore also be seen as an arrest of pulmonary development at this stage [3].Over a period of about 3 months the infant developed normally. The child underwent evaluation for possible lung transplantation. However, starting at the age of 13 weeks, the child developed sudden attacks of oxygen desaturation whilst breathing normally. The attacks were resistant to therapy. At the age of 101 days, the child did not recover from one of these attacks. An autopsy was not performed.The course of ACD/MPV in female siblings of one mother and two different fathers is different from the inheritance pattern in the literature and eliminates a possible recessive pedigree [5]. The first child died during the neonatal period (day 17), the second, reported here in detail, after 101 days of life, both of respiratory distress and permanent pulmonary hypertension (PPHN). When the second child showed similar symptoms after delivery, and after other causes for respiratory distress and PPHN had been ruled out, ACD/MPV was assumed, and subsequently proven.To date, ACD/MPV is a fatal disease [2,6]. Progress in lung transplantation in infants during the past years offers a therapeuti...

Congenital Alveolar Capillary Dysplasia and Associated Gastrointestinal Anomalies

“…The triad of intestinal malrotation, total colonic aganglionosis, and congenital capillary alveolar dysplasia as seen in one of our cases could be either a chance occurrence or probably due to a common embryonic migration defect. There may be a global delay in the expression and migration of two [6,[21][22][23] 6 Imperforate anus [12,14,18,24] 4 Aganglionosis=hypoganglionosis of colon [14][15][16]18] 4 Absent gallbladder [14,17,18] 3 Annular Pancreas [15,20] 2 Pyloric Stenosis [12] 1 Anal atresia [5] 1 Esophageal atresia with fistula [21] 1 Redundant colon [21] 1 Asplenia [25] 1 Atrioventricular (AV) malformation of liver [24] 1 Small intestinal diverticulum [26] 1 Ectopic pancreatic tissue in duodenum [27] 1 Postpyloric ectasy of small intestine [10] 1 common endodermal cell lines, resulting in delayed caudal migration of neuroectodermal cells into the colonic mesoderm, which commences between 35 and 49 days' gestation. Also there may be associated abnormality of vascularization of pulmonary mesenchyma, resulting in failure of formation and growth of alveolar capillary, reduced number of alveoli, hypertrophied alveolar walls, medial muscular thickening of small pulmonary arterioles, and anomalously situated pulmonary veins.…”

Infants and Young Children with Children's Interstitial Lung Disease

“…28 Rare reports document the potential for a later presentation and survival for months with therapy. 29 In a small series of 23 infants only half were suspected of having ACDMPV clinically before lung biopsy or postmortem analysis, suggesting that some cases may go undiagnosed. 28 The majority of patients reported also had at least one associated anomaly affecting the cardiovascular, gastrointestinal (GI), or genitourinary system.…”

Diagnostic Pathology of Diffuse Lung Disease in Children

“…ACD is fatal typically within the fi rst weeks of life, although rare reports of late presentation or prolonged survival into the fi rst year of life have been described. [47][48][49] In 2009, Stankiewicz et al discovered that many patients with ACD have either deletions of the FOX transcription factor gene cluster ( FOXF1 , FOXC2 , FOXL1 ) on chromosome 16q24.1 or point mutations of the FOXF1 gene. 50 As might be expected, patients with associated malformations often had deletions involving >1 gene in this cluster.…”